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Sample records for dose omeprazole infusion

  1. Omeprazole

    Science.gov (United States)

    Prescription omeprazole is used alone or with other medications to treat gastroesophageal reflux disease (GERD), a condition in which ... the tube between the throat and stomach). Prescription omeprazole is used to treat the symptoms of GERD, ...

  2. RELATIVE BIOAVAILABILITY OF OMEPRAZOLE CAPSULES AFTER ORAL DOSING

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    SAYED ABOLFAZL MOSTAFAVI

    2004-09-01

    Full Text Available Omeprazole, a proton pump inhibitor, effectively suppresses the gastric acid secretion in the parietal cells of stomach. Pharmacokinetics and relative bioavailability of generic products of omeprazole were compared with innovator product, Losec. Twelve healthy adult volunteers participated in the study which was conducted according to a randomized, open-label single dose Latin square cross over design. The preparations were compared using area under the plasma concentration – time curve (AUC, peak plasma concentration (Cmax, and time to reach peak plasma concentration (tmax. The two generic capsules proved to be bioequivalent with brand-name omeprazole with regard to the pharmacokinetic parameters Cmax, AUC0-t, AUC0-inf and tmax. Moreover the parametric confidence intervals (90% for the ratio of the Cmax, AUC0-8 and AUC0-∞ values lie between 0.8-1.2. The test formulations were found bioequivalent to the reference formulation by the one-way ANOVA test procedure. On the basis of these results, the 3 formulations were considered to be bioequivalent. Two subjects demonstrated increase in AUCs and high Cmax after administration of either product which may attribute to the ethnic disposition of omeprazole in these subjects.

  3. Antisecretory effect and oral pharmacokinetics following low dose omeprazole in man.

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    Howden, C W; Forrest, J A; Meredith, P A; Reid, J L

    1985-01-01

    The effects of single and repeated doses of omeprazole 10 mg on gastric secretion were studied in a group of six healthy subjects. Single doses had no significant effect on basal or stimulated acid output. After 7 days of treatment, there was a 93.1% reduction in basal acid output (P less than 0.02) and a 66.5% reduction in stimulated output (P less than 0.01). Pepsin output was not affected. Systemic availability of omeprazole, as reflected in the AUC, increased significantly (P less than 0.05) with repeated dosing. Low doses of omeprazole can produce substantial reductions in acid output after repeated dosing. PMID:3929808

  4. Effect of short-term treatment with regular or high doses of omeprazole on the detection of Helicobacter pylori in bleeding peptic ulcer patients.

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    Udd, M; Miettinen, P; Palmu, A; Julkunen, R

    2003-06-01

    It is unknown whether short-term regular or high-dose omeprazole has any influence on the colonization of Helicobacter pylori in the stomach. We therefore studied the effect of 3-day treatment of 2 different doses of omeprazole. H. pylori-positive patients with peptic ulcer bleeding (n = 101) were randomized to receive either a regular dose (20 mg/day for 3 days) (n = 51) or a high dose of omeprazole (80 mg bolus + 8 mg/h infusion/day for 3 days) (n = 50). H. pylori status was assessed by histology and urease testing of gastric biopsies pre-entry and after 3-day therapy. With the high dose of omeprazole, tests for the diagnosis of H. pylori became negative significantly more often than with the regular dose (60% versus 27.5%, P=0.001 (any test), 67.6% versus 31.7%, P=0.003 (histology) and 82.2% versus 43.6%, P=0.001 (urease test)). Conversion of the H. pylori tests negative after 3-day treatment of omeprazole is dose-dependent. The diagnosis of H. pylori infection depends on the timing of biopsies in relation to the beginning of proton-pump inhibitor treatment. If samples to find H. pylori are not taken before the treatment, the presence of the bacteria may be overlooked.

  5. Yosprala: A Fixed Dose Combination of Aspirin and Omeprazole.

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    Veltri, Keith T

    Cardiovascular disease is the leading cause of morbidity and mortality in the United States. Patients who survive a primary cerebrovascular or cardiovascular event are at increased risk of a subsequent occurrence. Antiplatelet therapy plays an essential role for secondary prevention in individuals with stroke, transient ischemic attack, acute or chronic artery disease, or peripheral arterial disease. Maintaining high-risk patients on low-dose aspirin therapy is a fundamental component of management. However, poor adherence, secondary to the drug's gastrointestinal side effects, has been associated with negative cardiovascular outcomes. Numerous studies have indicated that proton-pump inhibitors significantly reduce the risk of upper gastrointestinal adverse events in aspirin-treated patients. The US Food and Drug Administration approved Yosprala (Aralez Pharmaceuticals), a fixed-dose combination of delayed-release aspirin and immediate-release omeprazole, on September 15, 2016. It is the first product to become available in the United States that combines these 2 pharmacologic drug classes, and represents a new therapeutic option for patients and healthcare providers who strive to improve adherence to daily aspirin therapy.

  6. The effects of dose and diet on the pharmacodynamics of omeprazole in the horse.

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    Sykes, B W; Underwood, C; Greer, R; McGowan, C M; Mills, P C

    2017-07-01

    Conflicting data are presented in the current literature regarding the efficacy of omeprazole for suppressing gastric acidity in the horse. The objective of this study was to investigate the duration of intraday acid suppression achieved with two doses of omeprazole under two different dietary conditions. A four-way crossover design. Six adult Thoroughbred horses instrumented with percutaneous gastrotomy tubes were used. Intragastric pH was measured for continuous 23 h periods (08.00-07.00 h) for six consecutive days (Days 0-5). Baseline data was recorded on Day 0 and omeprazole administered on Days 1-5. Two doses (1 mg/kg and 4 mg/kg bwt per os once a day) and two diets (a high grain/low fibre [HG/LF] and ad libitum hay [HAY)] diet) were studied. Data for the percent (%) time pH was above 4 (%tpH>4) and median intraday pH was reported for two measurement locations and analysed using generalised estimating equations. An effect of both diet and dose was evident with mean %tpH>4 and the mean of the median intraday pHs typically higher at the higher (4 mg/kg bwt) dose and in HG/LF diet. The overall efficacy of omeprazole in raising intragastric pH was good under the HG/LF conditions but relatively poor in the HAY diet. A cumulative effect of dosing, not previously reported in the horse, was observed. The overall efficacy of omeprazole in raising ventral gastric pH was less than previously reported. Both dose and diet may play a role in the efficacy of omeprazole in the horse. Therefore, the use of singular dosing recommendations that encompass all horse types and management conditions may not be appropriate and dosing recommendations that take into account the diet of the horse may be advantageous. © 2016 EVJ Ltd.

  7. The effects of dose and diet on the pharmacokinetics of omeprazole in the horse.

    Science.gov (United States)

    Sykes, B W; Underwood, C; McGowan, C M; Mills, P C

    2017-04-01

    This study aimed to investigate the effect of diet and dose on the pharmacokinetics of omeprazole in the horse. Six horses received two doses (1 and 4 mg/kg) of omeprazole orally once daily for 5 days. Each dose was evaluated during feeding either a high-grain/low-fibre (HG/LF) diet or an ad libitum hay (HAY) diet in a four-way crossover design. Plasma samples were collected for pharmacokinetic analysis on days 1 and 5. Plasma omeprazole concentrations were determined by ultra-high pressure liquid chromatography-mass spectrometry. In horses being fed the HG/LF diet, on day 1, the area under the curve (AUC) and maximal plasma concentration (C max ) were higher on the 4 mg/kg dose than on the 1 mg/kg dose. The AUC was higher on day 5 compared to day 1 with the 4 mg/kg dose on the HG/LF diet. On days 1 and 5, the AUC and C max were higher in horses being fed the HG/LF diet and receiving the 4 mg/kg dose than in horses being fed the HAY diet and receiving the 1 mg/kg dose. These findings suggest that both dose and diet may affect pharmacokinetic variables of omeprazole in the horse. © 2016 John Wiley & Sons Ltd.

  8. Antisecretory effect and oral pharmacokinetics following low dose omeprazole in man.

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    Howden, C W; Forrest, J A; Meredith, P A; Reid, J L

    1985-01-01

    The effects of single and repeated doses of omeprazole 10 mg on gastric secretion were studied in a group of six healthy subjects. Single doses had no significant effect on basal or stimulated acid output. After 7 days of treatment, there was a 93.1% reduction in basal acid output (P less than 0.02) and a 66.5% reduction in stimulated output (P less than 0.01). Pepsin output was not affected. Systemic availability of omeprazole, as reflected in the AUC, increased significantly (P less than 0....

  9. Disposition of the anti-ulcer medications ranitidine, cimetidine, and omeprazole following administration of multiple doses to exercised Thoroughbred horses.

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    Knych, H K; Stanley, S D; Arthur, R M; McKemie, D S

    2017-01-01

    The use of anti-ulcer medications, such as cimetidine, ranitidine, and omeprazole, is common in performance horses. The use of these drugs is regulated in performance horses, and as such a withdrawal time is necessary prior to competition to avoid a medication violation. To the authors' knowledge, there are no reports in the literature describing repeated oral administrations of these drugs in the horse to determine a regulatory threshold and related withdrawal time recommendations. Therefore, the objective of the current study was to describe the disposition and elimination pharmacokinetics of these anti-ulcer medications following oral administration to provide data upon which appropriate regulatory recommendations can be established. Nine exercised Thoroughbred horses were administered 20 mg/kg BID of cimetidine or 8 mg/kg BID of ranitidine, both for seven doses or 2.28 g of omeprazole SID for four doses. Blood samples were collected, serum drug concentrations were determined, and elimination pharmacokinetic parameters were calculated. The serum elimination half-life was 7.05 ± 1.02, 7.43 ± 0.851 and 3.94 ± 1.04 h for cimetidine, ranitidine, and omeprazole, respectively. Serum cimetidine and ranitidine concentrations were above the LOQ and omeprazole and omeprazole sulfide below the LOQ in all horses studied upon termination of sample collection. © 2016 John Wiley & Sons Ltd.

  10. Drug-drug interaction of microdose and regular-dose omeprazole with a CYP2C19 inhibitor and inducer.

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    Park, Gab-Jin; Bae, Soo Hyeon; Park, Wan-Su; Han, Seunghoon; Park, Min-Ho; Shin, Seok-Ho; Shin, Young G; Yim, Dong-Seok

    2017-01-01

    A microdose drug-drug interaction (DDI) study may be a valuable tool for anticipating drug interaction at therapeutic doses. This study aimed to compare the magnitude of DDIs at microdoses and regular doses to explore the applicability of a microdose DDI study. Six healthy male volunteer subjects were enrolled into each DDI study of omeprazole (victim) and known perpetrators: fluconazole (inhibitor) and rifampin (inducer). For both studies, the microdose (100 μg, cold compound) and the regular dose (20 mg) of omeprazole were given at days 0 and 1, respectively. On days 2-9, the inhibitor or inducer was given daily, and the microdose and regular dose of omeprazole were repeated at days 8 and 9, respectively. Full omeprazole pharmacokinetic samplings were performed at days 0, 1, 8, and 9 of both studies for noncompartmental analysis. The magnitude of the DDI, the geometric mean ratios (with perpetrator/omeprazole only) of maximum concentration (C max ) and area under the curve to the last measurement (AUC t ) of the microdose and the regular dose were compared. The geometric mean ratios in the inhibition study were: 2.17 (micro) and 2.68 (regular) for C max , and 4.07 (micro), 4.33 (regular) for AUC t . For the induction study, they were 0.26 (micro) and 0.21 (regular) for C max , and 0.16 (micro) and 0.15 (regular) for AUC t . There were no significant statistical differences in the magnitudes of DDIs between microdose and regular-dose conditions, regardless of induction or inhibition. Our results may be used as partial evidence that microdose DDI studies may replace regular-dose studies, or at least be used for DDI-screening purposes.

  11. A STABILITY STUDY OF OMEPRAZOLE DILUTED IN SODIUM CHLORIDE FOR INTRAVENOUS INFUSION AND DISCUSSION REGARDING CURRENT PRACTICE IN UK PAEDIATRIC INTENSIVE CARE UNITS.

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    Morris, Stephen

    2016-09-01

    Omeprazole by intravenous infusion is occasionally warranted in children during episodes of acute upper gastro-intestinal bleeding. This is to ensure the continued suppression of stomach acid to reduce the of risk of re-bleeding.Current practice in UK paediatric intensive care units varies, but the use of 160 mg/1.73 m(3) over 24 hour has previously been reported.1 This is commonly prepared as a 0.8 mg/ml solution changed either at 12 or 24 hrs after preparation depending on reference source used.2 (-) 3 The current practice of using a 0.8 mg/ml (40 mg/50 ml) is off label and not endorsed by manufacturers who recommend a maximum concentration of 0.4 mg/ml3.Following these recommendations would lead to a fluid load of 400 ml/1.73 m(2) which is likely to be significant. Excess fluid intake has been shown to correlate with increased oxygenation index and increased PICU stay.4 The aim of this study is to provide stability data for using 0.8 mg/ml for intravenous infusion which is currently in widespread despite use a lack of published lack of data in this area. A series of analytical techniques were performed to assess physical and chemical stability. Test solutions were prepared by reconstituting Losec® (Omeprazole) 40 mg powder for infusion and diluting to either 50 ml or 100 ml in 0.9% sodium chloride.Reverse phase HPLC analysis was conducted at 0 hrs, 10 hrs and 24 hrs. Particle size was assessed using a zeta potential analyser at 15-minute intervals over 60 minutes. At both 40 mg/50 mL and 40 mg/100 mL the concentration of omeprazole remained at 101% and 100% after 10 hrs respectively. However significant degradation was seen at 24 hrs as concentrations reduced to 60% and 55% respectively.The difference between degradation after 10 hrs was not statistically significant when samples were compared using paired t-test with t(1)=1.25, p=0.427.Particle size analysis showed no statistical different between amount of particles in

  12. Drug–drug interaction of microdose and regular-dose omeprazole with a CYP2C19 inhibitor and inducer

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    Park G

    2017-03-01

    Full Text Available Gab-jin Park,1 Soo Hyeon Bae,1 Wan-Su Park,1 Seunghoon Han,1 Min-Ho Park,2 Seok-Ho Shin,2 Young G Shin,2 Dong-Seok Yim1,2 1Department of Clinical Pharmacology and Therapeutics, Seoul St Mary’s Hospital, PIPET (Pharmacometrics Institute for Practical Education and Training, College of Medicine, Catholic University of Korea, Seoul, South Korea; 2College of Pharmacy, Chungnam National University, Daejeon, South Korea Purpose: A microdose drug–drug interaction (DDI study may be a valuable tool for anticipating drug interaction at therapeutic doses. This study aimed to compare the magnitude of DDIs at microdoses and regular doses to explore the applicability of a microdose DDI study. Patients and methods: Six healthy male volunteer subjects were enrolled into each DDI study of omeprazole (victim and known perpetrators: fluconazole (inhibitor and rifampin (inducer. For both studies, the microdose (100 µg, cold compound and the regular dose (20 mg of omeprazole were given at days 0 and 1, respectively. On days 2–9, the inhibitor or inducer was given daily, and the microdose and regular dose of omeprazole were repeated at days 8 and 9, respectively. Full omeprazole pharmacokinetic samplings were performed at days 0, 1, 8, and 9 of both studies for noncompartmental analysis. Results: The magnitude of the DDI, the geometric mean ratios (with perpetrator/omeprazole only of maximum concentration (Cmax and area under the curve to the last measurement (AUCt of the microdose and the regular dose were compared. The geometric mean ratios in the inhibition study were: 2.17 (micro and 2.68 (regular for Cmax, and 4.07 (micro, 4.33 (regular for AUCt. For the induction study, they were 0.26 (micro and 0.21 (regular for Cmax, and 0.16 (micro and 0.15 (regular for AUCt. There were no significant statistical differences in the magnitudes of DDIs between microdose and regular-dose conditions, regardless of induction or inhibition. Conclusion: Our results may be

  13. Omeprazole-Domperidone Fixed Dose Combination vs Omeprazole Monotherapy: A Phase 4, Open-Label, Comparative, Parallel Randomized Controlled Study in Mild to Moderate Gastroesophageal Reflux Disease

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    KY Marakhouski

    2017-05-01

    Full Text Available Aim: To compare the efficacy and safety of omeprazole-domperidone combination vs omeprazole monotherapy in gastroesophageal reflux disease (GERD. Methods: In a comparative, randomized controlled, phase 4 study, outpatients with GERD were randomly allocated to either group 1 (omeprazole 20 mg + domperidone 30 mg or group 2 (omeprazole 20 mg in an equal ratio; 2 capsules daily in the morning were administered for 8 weeks. Results: Sixty patients were enrolled. Esophagitis reversal was observed in 92% patients in group 1 vs 65.2% in group 2. Approximately, 83.3% patients in group 1 vs 43.3% patients in group 2 demonstrated full cupping of reflux symptoms at 8 weeks. Combined therapy resulted in significantly longer period of heartburn-free days (23 vs 12 days on omeprazole. There were no safety concerns. Conclusions: Omeprazole-domperidone combination was more effective than omeprazole alone in providing complete cupping of reflux symptoms and healing of esophagitis in patients with GERD. Both the treatments were well tolerated with few reports of adverse events. Trial registration: This trial is registered with http://clinicaltrials.gov , number NCT02140073.

  14. Omeprazole-Domperidone Fixed Dose Combination vs Omeprazole Monotherapy: A Phase 4, Open-Label, Comparative, Parallel Randomized Controlled Study in Mild to Moderate Gastroesophageal Reflux Disease.

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    Marakhouski, K Y; Karaseva, G A; Ulasivich, D N; Marakhouski, Y Kh

    2017-01-01

    To compare the efficacy and safety of omeprazole-domperidone combination vs omeprazole monotherapy in gastroesophageal reflux disease (GERD). In a comparative, randomized controlled, phase 4 study, outpatients with GERD were randomly allocated to either group 1 (omeprazole 20 mg + domperidone 30 mg) or group 2 (omeprazole 20 mg) in an equal ratio; 2 capsules daily in the morning were administered for 8 weeks. Sixty patients were enrolled. Esophagitis reversal was observed in 92% patients in group 1 vs 65.2% in group 2. Approximately, 83.3% patients in group 1 vs 43.3% patients in group 2 demonstrated full cupping of reflux symptoms at 8 weeks. Combined therapy resulted in significantly longer period of heartburn-free days (23 vs 12 days on omeprazole). There were no safety concerns. Omeprazole-domperidone combination was more effective than omeprazole alone in providing complete cupping of reflux symptoms and healing of esophagitis in patients with GERD. Both the treatments were well tolerated with few reports of adverse events. This trial is registered with http://clinicaltrials.gov, number NCT02140073.

  15. Chicken parathyroid hormone gene expression in response to gastrin, omeprazole, ergocalciferol, and restricted food intake.

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    Gagnemo-Persson, R; Samuelsson, A; Hâkanson, R; Persson, P

    1997-09-01

    Treatment with omeprazole, a long-acting proton pump inhibitor of acid secretion, induces hypergastrinemia. In chickens, omeprazole induces growth not only of the acid-producing mucosa (probably reflecting the trophic action of gastrin), but also of the parathyroid glands (hypertrophy + hyperplasia), while suppressing bone density and body weight gain without affecting blood calcium. The first part of the present study was concerned with the effect of omeprazole, ergocalciferol (vitamin D2), and restricted food intake on the gene expression of parathyroid hormone (PTH) in the parathyroid glands of the chicken. Chickens were treated with omeprazole (400 micromol/kg/day, I.M.), food restriction, omeprazole + food restriction, ergocalciferol (250 000 IU/kg/day, S.C.), or ergocalciferol + omeprazole for 5 weeks. The weight gain of the chickens was monitored, and the weights of the parathyroid glands and femurs were determined at sacrifice. PTH mRNA in the parathyroid glands was analyzed by Northern blot. The second part of the study examined the effect of 3 weeks of continuous gastrin infusion (chicken gastrin 20-36, 5 nmol/kg/hour, S.C.) on the expression of PTH mRNA in the parathyroid glands. Omeprazole reduced the body weight and femur density (ash weight per volume) while greatly increasing the weight of the parathyroid glands and the PTH gene expression. Food restriction alone and ergocalciferol alone (at a dose that raised blood Ca2+) were without effect, but food restriction greatly enhanced the omeprazole-evoked increase in parathyroid gland weight and PTH gene expression. Gastrin increased the weight of the parathyroid glands and reproduced the effect of omeprazole on PTH gene expression. Hence, it seems likely that the effect of omeprazole reflects the ensuing hypergastrinemia.

  16. Dose-Finding Study of Omeprazole on Gastric pH in Neonates with Gastro-Esophageal Acid Reflux Using a Bayesian Sequential Approach.

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    Kaguelidou, Florentia; Alberti, Corinne; Biran, Valerie; Bourdon, Olivier; Farnoux, Caroline; Zohar, Sarah; Jacqz-Aigrain, Evelyne

    2016-01-01

    Proton pump inhibitors are frequently administered on clinical symptoms in neonates but benefit remains controversial. Clinical trials validating omeprazole dosage in neonates are limited. The objective of this trial was to determine the minimum effective dose (MED) of omeprazole to treat pathological acid reflux in neonates using reflux index as surrogate marker. Double blind dose-finding trial with continual reassessment method of individual dose administration using a Bayesian approach, aiming to select drug dose as close as possible to the predefined target level of efficacy (with a credibility interval of 95%). Neonatal Intensive Care unit of the Robert Debré University Hospital in Paris, France. Neonates with a postmenstrual age ≥ 35 weeks and a pathologic 24-hour intra-esophageal pH monitoring defined by a reflux index ≥ 5% over 24 hours were considered for participation. Recruitment was stratified to 3 groups according to gestational age at birth. Five preselected doses of oral omeprazole from 1 to 3 mg/kg/day. Primary outcome, measured at 35 weeks postmenstrual age or more, was a reflux index <5% during the 24-h pH monitoring registered 72±24 hours after omeprazole initiation. Fifty-four neonates with a reflux index ranging from 5.06 to 27.7% were included. Median age was 37.5 days and median postmenstrual age was 36 weeks. In neonates born at less than 32 weeks of GA (n = 30), the MED was 2.5mg/kg/day with an estimated mean posterior probability of success of 97.7% (95% credibility interval: 90.3-99.7%). The MED was 1mg/kg/day for neonates born at more than 32 GA (n = 24). Omeprazole is extensively prescribed on clinical symptoms but efficacy is not demonstrated while safety concerns do exist. When treatment is required, the daily dose needs to be validated in preterm and term neonates. Optimal doses of omeprazole to increase gastric pH and decrease reflux index below 5% over 24 hours, determined using an adaptive Bayesian design differ among

  17. Dose-Finding Study of Omeprazole on Gastric pH in Neonates with Gastro-Esophageal Acid Reflux Using a Bayesian Sequential Approach.

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    Florentia Kaguelidou

    Full Text Available Proton pump inhibitors are frequently administered on clinical symptoms in neonates but benefit remains controversial. Clinical trials validating omeprazole dosage in neonates are limited. The objective of this trial was to determine the minimum effective dose (MED of omeprazole to treat pathological acid reflux in neonates using reflux index as surrogate marker.Double blind dose-finding trial with continual reassessment method of individual dose administration using a Bayesian approach, aiming to select drug dose as close as possible to the predefined target level of efficacy (with a credibility interval of 95%.Neonatal Intensive Care unit of the Robert Debré University Hospital in Paris, France.Neonates with a postmenstrual age ≥ 35 weeks and a pathologic 24-hour intra-esophageal pH monitoring defined by a reflux index ≥ 5% over 24 hours were considered for participation. Recruitment was stratified to 3 groups according to gestational age at birth.Five preselected doses of oral omeprazole from 1 to 3 mg/kg/day.Primary outcome, measured at 35 weeks postmenstrual age or more, was a reflux index <5% during the 24-h pH monitoring registered 72±24 hours after omeprazole initiation.Fifty-four neonates with a reflux index ranging from 5.06 to 27.7% were included. Median age was 37.5 days and median postmenstrual age was 36 weeks. In neonates born at less than 32 weeks of GA (n = 30, the MED was 2.5mg/kg/day with an estimated mean posterior probability of success of 97.7% (95% credibility interval: 90.3-99.7%. The MED was 1mg/kg/day for neonates born at more than 32 GA (n = 24.Omeprazole is extensively prescribed on clinical symptoms but efficacy is not demonstrated while safety concerns do exist. When treatment is required, the daily dose needs to be validated in preterm and term neonates. Optimal doses of omeprazole to increase gastric pH and decrease reflux index below 5% over 24 hours, determined using an adaptive Bayesian design differ

  18. Influence of Food on the Bioavailability of an Enteric-Coated Tablet Formulation of Omeprazole 20 mg Under Repeated Dose Conditions

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    ABR Thomson

    1997-01-01

    Full Text Available The objective of this study was to investigate the influence of food on the bioavailability of omeprazole (20 mg given as an enteric-coated tablet under repeated dose conditions. This open randomized crossover study consisted of three seven-day treatment periods, each separated by a drug-free period. During each treatment period an enteric-coated tablet of omeprazole was taken once daily either under fasting conditions, or immediately before or after a standardized breakfast. On the last day of each treatment period, blood samples for the determination of plasma omeprazole concentrations were collected at baseline and at predetermined intervals over the 24 h period following drug administration. Fifty-seven male and female subjects, aged 18 to 52 years, completed the study according to the protocol. No statistically significant differences were found when comparing either the before breakfast or after breakfast treatment regimens with the fasting regimen for the estimated mean area under the plasma concentration-time curve (AUC. The maximum plasma concentration was not found to differ significantly among any of the treatment regimens. However, the lower limit of the CI for the comparison of fasting/before breakfast was not contained within the limits of bioequivalence. The time to reach maximum plasma concentration was significantly different when fasting and after breakfast regimens were compared. Thus, under repeated dose conditions, food has no influence on the bioavailability (expressed as AUC of omeprazole given as the enteric-coated tablet formulation.

  19. Comparison of the effect of a single dose of omeprazole or lansoprazole on intragastric pH in Japanese participants: a two-way crossover study.

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    Funaki, Yasushi; Tokudome, Kentaro; Izawa, Shinya; Tamura, Yasuhiro; Kondo, Yoshihiro; Iida, Akihito; Mizuno, Mari; Ogasawara, Naotaka; Sasaki, Makoto; Kasugai, Kunio

    2013-03-01

    It is known that the pharmacokinetic profile of proton pump inhibitors (PPIs) after postprandial administration may differ among PPIs. The purpose of this study was to compare the inhibitory effects of gastric acid secretion by PPIs administered after a meal, based on a 24-hour intragastric pH monitoring. Ten healthy men who provided written informed consent participated in the study. They were given a 20-mg omeprazole tablet and a 30-mg lansoprazole orally dispersing tablet in a two-way crossover manner. At baseline, the anti-HP-IgG antibody levels in blood and the pepsinogen (PG) I/II ratio were measured. Participants were given a standardized meal and 200 mL of water at 9:30 am, 13:30 pm, and 18.30 pm. Participants took the PPI after breakfast. Two of the ten participants tested positive for Helicobacter pylori infection. The PG I/II ratio indicated negative gastric atrophy in all the participants. The percentage 24-hour intragastric pH > 4 holding times (median, range) with omeprazole and lansoprazole were 29.3, 19.3-50.0% and 27.8, 13.0-42.3%, respectively, which shows that with the administration of omeprazole, the pH was maintained at >4 for a longer period (p lansoprazole (p lansoprazole, a single postprandial dose of omeprazole showed a more rapid and sustained acid-inhibitory effect. Copyright © 2012. Published by Elsevier B.V.

  20. Comparative Dose Accuracy of Durable and Patch Insulin Infusion Pumps

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    Jahn, Luis G.; Capurro, Jorge J.; Levy, Brian L.

    2013-01-01

    Background: As all major insulin pump manufacturers comply with the international infusion pump standard EN 60601-2-24:1998, there may be a general assumption that all pumps are equal in insulin-delivery accuracy. This research investigates single-dose and averaged-dose accuracy of incremental basal deliveries for one patch model and three durable models of insulin pumps. Method: For each pump model, discrete single doses delivered during 0.5 U/h basal rate infusion over a 20 h period were measured using a time-stamped microgravimetric system. Dose accuracy was analyzed by comparing single doses and time-averaged doses to specific accuracy thresholds (±5% to ±30%). Results: The percentage of single doses delivered outside accuracy thresholds of ±5%, ±10%, and ±20% were as follows: Animas OneTouch® Ping® (43.2%, 14.3%, and 1.8%, respectively), Roche Accu-Chek® Combo (50.6%, 24.4%, and 5.5%), Medtronic Paradigm® RevelTM/VeoTM (54.2%, 26.7%, and 6.6%), and Insulet OmniPod® (79.1%, 60.5%, and 34.9%). For 30 min, 1 h, and 2 h averaging windows, the percentage of doses delivered outside a ±15% accuracy were as follows: OneTouch Ping (1.0%, 0.4%, and 0%, respectively), Accu-Chek Combo (4.2%, 3.5%, and 3.1%), Paradigm Revel/Veo (3.9%, 3.1%, and 2.2%), and OmniPod (33.9%, 19.9%, and 10.3%). Conclusions: This technical evaluation demonstrates significant differences in single-dose and averaged-dose accuracy among the insulin pumps tested. Differences in dose accuracy were most evident between the patch pump model and the group of durable pump models. Of the pumps studied, the Animas OneTouch Ping demonstrated the best single-dose and averaged-dose accuracy. Further research on the clinical relevance of these findings is warranted. PMID:23911184

  1. Once-daily omeprazole/sodium bicarbonate heals severe refractory reflux esophagitis with morning or nighttime dosing.

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    Orbelo, Diana M; Enders, Felicity T; Romero, Yvonne; Francis, Dawn L; Achem, Sami R; Dabade, Tushar S; Crowell, Michael D; Geno, Debra M; DeJesus, Ramona S; Namasivayam, Vikneswaran; Adamson, Steven C; Arora, Amindra S; Majka, Andrew J; Alexander, Jeffrey A; Murray, Joseph A; Lohse, Matthew; Diehl, Nancy N; Fredericksen, Mary; Jung, Kee Wook; Houston, Margaret S; O'Neil, Angela E; Katzka, David A

    2015-01-01

    Morning dose or twice-daily proton pump inhibitor (PPI) use is often prescribed to heal severe reflux esophagitis. Compare the effect of single dose morning (control arm) versus nighttime (experimental arm) omeprazole/sodium bicarbonate (Zegerid(®)) (IR-OME) on esophagitis and gastroesophageal reflux symptoms. Adult outpatients with Los Angeles grade C or D esophagitis were allocated to open-label 40 mg IR-OME once a day for 8 weeks in a prospective, randomized, parallel design, single center study. Esophagogastroduodenoscopy (EGD) and validated self-report symptom questionnaires were completed at baseline and follow-up. Intention-to-treat and per-protocol analyses were performed. Ninety-two of 128 (72 %) eligible subjects participated [64 (70 %) male, mean age 58 (range 19-86), median BMI 29 (range 21-51), 58 C:34 D]. Overall, 81 (88 %) subjects healed [n = 70 (76 %)] or improved [n = 11 (12 %)] erosions. There was no significant difference (morning vs. night) in mucosal healing [81 vs. 71 %, (p = 0.44)] or symptom resolution [heartburn (77 vs. 65 %, p = 0.12), acid regurgitation (82 vs. 73 %, p = 0.28)]. Prevalence of newly identified Barrett's esophagus was 14 % with half diagnosed only after treatment. Once-daily IR-OME (taken morning or night) effectively heals severe reflux esophagitis and improves GERD symptoms. Results support the clinical practice recommendation to repeat EGD after 8 weeks PPI therapy in severe esophagitis patients to assure healing and exclude Barrett's esophagus.

  2. Twice-daily dosing of esomeprazole effectively inhibits acid secretion in CYP2C19 rapid metabolisers compared with twice-daily omeprazole, rabeprazole or lansoprazole.

    Science.gov (United States)

    Sahara, S; Sugimoto, M; Uotani, T; Ichikawa, H; Yamade, M; Iwaizumi, M; Yamada, T; Osawa, S; Sugimoto, K; Umemura, K; Miyajima, H; Furuta, T

    2013-11-01

    Twice-daily dosing of proton pump inhibitors (PPIs) is used to treat Helicobacter pylori or acid-related diseases, such as gastro-oesophageal reflux disease (GERD) refractory to standard dose of a PPI. Genetic polymorphisms of CYP2C19 are involved to different extents in the metabolism of four kinds of PPIs (omeprazole, lansoprazole, rabeprazole and esomeprazole) available in Japan. To compare acid-inhibitory effects of the four PPIs dosed twice daily in relation to CYP2C19 genotype. We performed 24-h pH monitoring studies on Day 7 of PPI treatment for 40 Japanese H. pylori-negative volunteers [15 CYP2C19 rapid metabolisers (RMs), 15 intermediate metabolisers (IMs) and 10 poor metabolisers (PMs)] using a randomised four-way crossover design: omeprazole 20 mg, esomeprazole 20 mg, lansoprazole 30 mg and rabeprazole 10 mg twice daily. Although median pH values with esomeprazole, omeprazole, lansoprazole and rabeprazole were 5.7 (3.5-7.2), 5.5 (2.4-7.2), 5.5 (3.7-7.3) and 5.2 (2.5-7.3), respectively (no statistically significant differences), CYP2C19 genotype-dependent differences were smaller for esomeprazole and rabeprazole compared with values for omeprazole and lansoprazole. In CYP2C19 RMs, the median pH with esomeprazole [5.4 (3.5-6.8)] was significantly higher than those with omeprazole [5.0 (2.4-5.9), P = 0.018], lansoprazole [4.7 (3.7-5.5), P = 0.017] or rabeprazole [4.8 (2.5-6.4), P = 0.002]. In IMs and PMs, the median pH was >5.0 independent of the PPI. In intermediate and rapid metabolisers of CYP2C19, PPIs dosed twice daily could attain sufficient acid suppression, while in CYP2C19 RMs, esomeprazole 20 mg twice daily caused the strongest inhibition of the four PPIs. Therefore, esomeprazole may be effective in Japanese population when dosed twice daily. © 2013 John Wiley & Sons Ltd.

  3. Continuous Intravenous Sub-Dissociative Dose Ketamine Infusion for Managing Pain in the Emergency Department

    OpenAIRE

    Motov, Sergey; Drapkin, Jefferson; Likourezos, Antonios; Beals, Tyler; Monfort, Ralph; Fromm, Christian; Marshall, John

    2018-01-01

    Introduction: Our objective was to describe dosing, duration, and pre- and post-infusion analgesic administration of continuous intravenous sub-dissociative dose ketamine (SDK) infusion for managing a variety of painful conditions in the emergency department (ED).  Methods: We conducted a retrospective chart review of patients aged 18 and older presenting to the ED with acute and chronic painful conditions who received continuous SDK infusion in the ED for a pe...

  4. Drug interaction: Omeprazole and Phenprocoumon

    Directory of Open Access Journals (Sweden)

    Müller Willi

    2001-04-01

    Full Text Available Abstract Background Oral anticoagulants like the coumarin derivatives are characterised by a particularly narrow therapeutic range. Any interfering co-medication can pose a challenge to establishing a stable anticoagulant dosage regimen and thus present a serious risk for the patient. Here we describe two cases of patients on anticoagulant therapy that suggest possible drug interactions between phenprocoumon and the proton pump inhibitor omeprazole. Results In both patients, the International Normalised Ratio (INR increased beyond the therapeutic range after they were given omeprazole for the treatment of gastrointestinal symptoms. The INR returned to therapeutic levels after the phenprocoumon dose was reduced (Case 1 and omeprazole discontinued (Case 2. Conclusions The increased anticoagulant activity of phenprocoumon observed in the two described cases and the known interaction potential of omeprazole suggest that the clearance of phenprocoumon may have been reduced due to competitive inhibition of its degradation by omeprazole. Drug interactions may be one of the reasons for the difficulties encountered with some patients in establishing a stable anticoagulant therapy. Physicians should carefully review any concurrently used medication and if possible opt for drugs with a low interaction potential.

  5. The Effect of Low-Dose Oxytocin Infusion on Cerebral Hemodynamics in Pregnant Women

    NARCIS (Netherlands)

    van Veen, Teelkien R.; Belfort, Michael A.; Zeeman, Gerda G.

    We investigated the cerebrovascular effects of continuous infusion of low-dose oxytocin in normal pregnant women undergoing induction of labor. In our prospective observational study, middle cerebral artery velocity was measured with transcranial Doppler ultrasound in 25 healthy, normotensive,

  6. Investigation of initial contamination for disposal medical infusion items and determination of sterilization dose

    International Nuclear Information System (INIS)

    Hu Jinhui; Xu Ziyan; Sun Naifeng; Yan Aoshuang; Gao Wei; Wang Binglin

    1993-01-01

    Statistical analyses on initial contamination of 624 disposal medical infusion items are made. The normal distribution of the initial contamination, the relation of initial contamination of inner and outer walls of disposal medical infusion items and the changes of initial contamination before irradiation are shown. The sterilized dose for disposal infusion is determined as 17.2 kGy using bioburden information. The SAL (sterility assurance level) dose is 10 6 . The SIP (device sample item proportion) is 1 and the average initial contamination is 7 CFU/item

  7. Bioavailability of two single-dose oral formulations of omeprazole 20 mg: an open-label, randomized sequence, two-period crossover comparison in healthy Mexican adult volunteers.

    Science.gov (United States)

    Poo, Jorge Luis; Galán, Juan Francisco; Rosete, Alejandra; de Lago, Alberto; Oliva, Iván; González-de la Parra, Mario; Jiménez, Patricia; Burke-Fraga, Victoria; Namur, Salvador

    2008-04-01

    Omeprazole is a proton-pump inhibitor that acts to reduce acid secretion in the stomach and is used for treating various acid-related gastrointestinal disorders. There are several generic formulations of omeprazole available in Mexico; however, a literature search failed to identify published data concerning the bioavailability of these formulations in the Mexican population. The aim of this study was to compare the bioavailability of 2 oral formulations of omeprazole 20-mg capsules, marketed for use in Mexico, in healthy volunteers: Inhibitron (test formulation) and LosecA 20 mg (reference formulation). This study used a single-dose, open-label, randomized sequence, 2 x 2 crossover (2 administration periods x 2 treatments) design to compare the 2 formulations. Eligible subjects were healthy adult Mexican volunteers of both sexes. Subjects were randomly assigned in a 1:1 ratio to receive a single 20-mg dose of the test formulation followed by the reference formulation, or vice versa, with a 7-day washout period between administration periods. After a 12-hour (overnight) fast, subjects received a single, 20-mg dose of the corresponding formulation. Plasma samples were obtained over a 12-hour period after administration. Plasma omeprazole concentrations were analyzed by a nonstereospecific high-performance liquid chromatography method. For analysis of pharmacokinetic properties, including C(max), AUC from time 0 (baseline) to time t (AUC(0-t)), and AUC from baseline to infinity (AUC(0-infinity)), blood samples were drawn at baseline and 0.17, 0.33, 0.50, 0.75, 1, 1.25, 1.50, 1.75, 2, 2.50, 3, 4, 6, 8, and 12 hours after administration. The formulations were considered bioequivalent if the natural log (ln)-transformed ratios of C(max) and AUC were within the predetermined equivalence range of 80% to 125%, and if P disability, or required intervention to prevent permanent impairment or damage. Thirty-four subjects were enrolled and completed the study (25 men and 9

  8. Effects of different omeprazole dosing on gastric pH in non-variceal upper gastrointestinal bleeding: A randomized prospective study.

    Science.gov (United States)

    Chwiesko, Adam; Charkiewicz, Radoslaw; Niklinski, Jacek; Luczaj, Wojciech; Skrzydlewska, Elzbieta; Milewski, Robert; Baniukiewicz, Andrzej; Wroblewski, Eugeniusz; Rosolowski, Mariusz; Dabrowski, Andrzej

    2016-09-01

    We aimed to identify the best method of omeprazole (OME) application with respect to intragastric pH, cytochrome P450 2C19 (CYP2C19) genotype and phenotype. The patients with non-variceal upper gastrointestinal bleeding (NVUGIB) were prospectively enrolled. After the achievement of endoscopic hemostasis, the patients were randomized to 40-mg intravenous (i.v.) OME bolus injection every 12 h or 8-mg/h continuous i.v. infusion for 72 h after an 80-mg i.v. OME bolus administration. The intragastric pH was recorded for 72 h. The CYP2C19 variant alleles (*2, *3, *17) were analyzed and the serum concentrations of OME and 5-hydroxyomeprazole (5-OH OME) were determined. Altogether 41 Caucasians (18 in the OME infusion [OI] group and 23 in the OME bolus [OB] group) were analyzed. The median percentage of time with an intragastric pH > 4.0 was higher in the infusion group than in the OB group over 48 h (100% vs 96.6%, P = 0.009) and 72 h (100% vs 87.6%, P = 0.006), and that at an intragastric pH >6.0 was higher in the OI group than the OB group over 72 h (97.9% vs 63.5%, P = 0.04). Helicobacter pylori infection was correlated with the fastest increase in intragastric pH, especially in the OI group. In both groups, CYP2C19 genotypes (*1/*1, *1/*17, *17/*17) had no essential effect on intragastric pH. In patients with NVUGIB, OME i.v. bolus followed by continuous infusion is more effective than OME i.v. bolus every 12 h in maintaining higher intragastric pH, regardless of CYP2C19 genetic polymorphisms. H. pylori infection accelerates the initial elevation of intragastric pH. © 2016 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

  9. Variable omeprazole kinetics in healthy Jordanian adults.

    Science.gov (United States)

    Albsoul-Younes, Abla; Tayyem, Rabab; Najib, Naji

    2005-07-01

    The objective of this study was to examine the pharmacokinetics of orally administered omeprazole in healthy adult Jordanian men. Plasma concentrations of omeprazole were measured over a 12 h period after administration of a single oral dose of 40 mg omeprazole (Losec), AstraZeneca, UK). Subjects were healthy adult Jordanian men age 18-38 (24 +/- 4, mean +/- SD). The pharmacokinetic parameters were derived from the plasma concentration-time profiles for AUC(0-t), AUC(0-inf), C(max), t(max), t(1/2e) and K(e). The pharmacokinetic of omeprazole were scattered over a wide range. The median AUC(0-inf) was 784.86 +/- 1182.88 (ng.h/ml), and the median C(max) was 521 +/- 354 (ng/ml) (median +/- SD). In general, most subjects showed normal distribution (approximately 90%). Some subjects (10%) did show very high AUC and C(max) compared with the reported AUC and C(max) levels. These subjects had higher half-lives and lower rates of elimination. Significant difference in the pharmacokinetics of omeprazole after a single dose administration was noted. Approximately 10% of the study group showed very high omeprazole plasma levels and AUCs. Differences in the pharmacokinetics might be due to differences in the genetic make-up of subjects. Copyright 2005 John Wiley & Sons, Ltd.

  10. Refractory metabolic acidosis as a complication of high-dose midazolam infusion for pediatric status epilepticus.

    Science.gov (United States)

    Federman, Myke D; Kelly, Robert; Harrison, Rick E

    2009-01-01

    The use of midazolam for the treatment of status epilepticus in children has generally been shown to be well tolerated and safe. Furthermore, encouraging efficacy has been observed when pediatric patients with status epilepticus have received continuous intravenous infusions of midazolam. A 9-year-old girl was treated with high-dose, continuous intravenous infusion of midazolam for the management of refractory status epilepticus. The patient developed a severe hyperchloremic, non-anion gap metabolic acidosis and resultant hemodynamic compromise, necessitating significant inotropic support and the initiation of a vasopressor infusion. We speculate that this complication was due to the preparation of parenteral midazolam with hydrochloric acid. The midazolam infusion was stopped, and, in less than 5 hours, the patient's metabolic acidosis resolved. The patient's inotropic and vasopressor infusions could only be weaned after discontinuing the use of high-dose midazolam. Although this complication was observed in only 1 pediatric patient with cortical dysplasia, caution and close clinical and laboratory surveillance should be exercised when administering continuous intravenous infusions of midazolam to pediatric patients.

  11. Dose response of subcutaneous GLP-1 infusion in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Torekov, Signe Sørensen; Kipnes, M S; Harley, R E

    2011-01-01

    To evaluate the dose-response relationship of the recombinant glucagon-like peptide-1 (7-36) amide (rGLP-1) administered by continuous subcutaneous infusion (CSCI) in subjects with type 2 diabetes, with respect to reductions in fasting, postprandial and 11-h serum glucose profiles.......To evaluate the dose-response relationship of the recombinant glucagon-like peptide-1 (7-36) amide (rGLP-1) administered by continuous subcutaneous infusion (CSCI) in subjects with type 2 diabetes, with respect to reductions in fasting, postprandial and 11-h serum glucose profiles....

  12. Omeprazole inhibits proliferation and modulates autophagy in pancreatic cancer cells.

    Directory of Open Access Journals (Sweden)

    Andrej Udelnow

    Full Text Available BACKGROUND: Omeprazole has recently been described as a modulator of tumour chemoresistance, although its underlying molecular mechanisms remain controversial. Since pancreatic tumours are highly chemoresistant, a logical step would be to investigate the pharmacodynamic, morphological and biochemical effects of omeprazole on pancreatic cancer cell lines. METHODOLOGY/PRINCIPAL FINDINGS: Dose-effect curves of omeprazole, pantoprazole, gemcitabine, 5-fluorouracil and the combinations of omeprazole and 5-fluorouracil or gemcitabine were generated for the pancreatic cancer cell lines MiaPaCa-2, ASPC-1, Colo357, PancTu-1, Panc1 and Panc89. They revealed that omeprazole inhibited proliferation at probably non-toxic concentrations and reversed the hormesis phenomena of 5-fluorouracil. Electron microscopy showed that omeprazole led to accumulation of phagophores and early autophagosomes in ASPC-1 and MiaPaCa-2 cells. Signal changes indicating inhibited proliferation and programmed cell death were found by proton NMR spectroscopy of both cell lines when treated with omeprazole which was identified intracellularly. Omeprazole modulates the lysosomal transport pathway as shown by Western blot analysis of the expression of LAMP-1, Cathepsin-D and β-COP in lysosome- and Golgi complex containing cell fractions. Acridine orange staining revealed that the pump function of the vATPase was not specifically inhibited by omeprazole. Gene expression of the autophagy-related LC3 gene as well as of Bad, Mdr-1, Atg12 and the vATPase was analysed after treatment of cells with 5-fluorouracil and omeprazole and confirmed the above mentioned results. CONCLUSIONS: We hypothesise that omeprazole interacts with the regulatory functions of the vATPase without inhibiting its pump function. A modulation of the lysosomal transport pathway and autophagy is caused in pancreatic cancer cells leading to programmed cell death. This may circumvent common resistance mechanisms of

  13. Aspirin and Omeprazole

    Science.gov (United States)

    The combination of aspirin and omeprazole is used to reduce the risk of stroke or heart attack in patients who have had or ... risk of developing a stomach ulcer when taking aspirin. Aspirin is in a class of medications called ...

  14. Healing of chronic Barrett ulcers with omeprazole

    NARCIS (Netherlands)

    Hameeteman, W.; Tytgat, G. N.

    1986-01-01

    Three patients with a long-standing benign Barrett ulcer, resistant to treatment with high doses of either cimetidine or ranitidine, given for at least 3 months, were treated with 40 mg omeprazole daily for 9 wk. After 2 wk all symptoms had disappeared and at the end of treatment all three patients

  15. Extended duration of prehydration does not prevent nephrotoxicity or delayed drug elimination in high-dose methotrexate infusions

    DEFF Research Database (Denmark)

    Mikkelsen, Torben Stamm; Mamoudou, Aissata Diop; Tuckuviene, Ruta

    2014-01-01

    Alkalized hydration is used as supportive care to prevent renal toxicity during infusions with high-dose methotrexate (HDMTX). In children with acute lymphoblastic leukemia (ALL), the hydration is commonly initiated 4 hours before start of the methotrexate (MTX) infusion. To test if longer duration...... of prehydration would prevent MTX-induced renal toxicity, we preformed a randomized cross-over study comparing 12-4 hours of hydration before the infusion of HDMTX....

  16. Accidental intravenous infusion of a large dose of magnesium sulphate during labor: A case report

    Directory of Open Access Journals (Sweden)

    Kamal Kumar

    2013-01-01

    Full Text Available During labor and child delivery, a wide range of drugs are administered. Most of these medications are high-alert medications, which can cause significant harm to the patient due to its inadvertent use. Errors could be caused due to unfamiliarity with safe dosage ranges, confusion between similar looking drugs, mislabeling of drugs, equipment misuse, or malfunction and communication errors. We report a case of inadvertent infusion of a large dose of magnesium sulphate in a pregnant woman.

  17. Elimination of ascorbic acid after high-dose infusion in prostate cancer patients

    DEFF Research Database (Denmark)

    Nielsen, Torben Kjær; Højgaard, Martin; Andersen, Jon Thor Trærup

    2015-01-01

    Treatment with high-dose intravenous (IV) ascorbic acid (AA) is used in complementary and alternative medicine for various conditions including cancer. Cytotoxicity to cancer cell lines has been observed with millimolar concentrations of AA. Little is known about the pharmacokinetics of high dose...... infusion stop in prostate cancer patients with normal kidney function. We propose a regimen with a bolus loading followed by a maintenance infusion based on the calculated clearance.......Treatment with high-dose intravenous (IV) ascorbic acid (AA) is used in complementary and alternative medicine for various conditions including cancer. Cytotoxicity to cancer cell lines has been observed with millimolar concentrations of AA. Little is known about the pharmacokinetics of high dose...... IV AA. The purpose of the present study was to assess the basic kinetic variables in human beings over a relevant AA dosing interval for proper design of future clinical trials. Ten patients with metastatic prostate cancer were treated for four weeks with fixed AA doses of 5, 30 and 60 g. AA...

  18. Impact of physical parameters on dosing errors due to a syringe exchange in multi-infusion therapy

    NARCIS (Netherlands)

    Snijder, Roland A.; Konings, Maurits K.; van den Hoogen, Agnes; Timmerman, Annemoon M.D.E.

    2017-01-01

    Introduction Infusion therapy is challenging and dosing errors may occur due to physical phenomena related to the infusion hardware, despite the use of accurate syringe pumps. These errors typically occur after interventions, such as the exchange of a syringe. We aimed to characterize and quantify

  19. Lower dose basal insulin infusion has positive effect on glycaemic control for children with type I diabetes on continuous subcutaneous insulin infusion therapy

    NARCIS (Netherlands)

    Schulten, Ron J; Piet, Jessica; Bruijning-Verhagen, Patricia; de Waal, Wouter J

    2017-01-01

    Objective: The aim of our study was to explore a possible relationship between proportion of basal insulin dose (%BD/T) and glycaemic control in children with type I diabetes on continuous subcutaneous insulin infusion (CSII) therapy. Methods: All patients under the age of 18 with type I diabetes

  20. Efficacy of omeprazole/sodium bicarbonate treatment in gastroesophageal reflux disease: a systematic review.

    Science.gov (United States)

    Higuera-de-la-Tijera, Fátima

    2018-03-14

    Proton pump inhibitors are the most effective medical therapy for gastroesophageal reflux disease, but their onset of action may be slow. To assess the available literature regarding the efficacy of omeprazole/sodium bicarbonate in gastroesophageal reflux patients. A systematic review was conducted. A systematic literature search starting from 2000. Reviewed manuscripts concerning the effectiveness of omeprazole/sodium bicarbonate treatment in gastroesophageal reflux disease were reviewed and the data were extracted. Data were subsequently analyzed with descriptive statistics. This review included information of four studies. Two trials compared the efficacy of omeprazole/sodium bicarbonate versus omeprazole. One study compared the efficacy of once-daily morning or nighttime dosing. And another study compared omeprazole/sodium bicarbonate/alginate versus omeprazole. In total, there was no difference between omeprazole/sodium bicarbonate and omeprazole. However, there is a trend towards more sustained response and a greater proportion of patients with sustained total relief by 30 minutes with omeprazole/sodium bicarbonate. Omeprazole/sodium bicarbonate therapy is not more effective than omeprazole in the treatment of gastroesophageal reflux disease. However, data obtained suggest that it can have a more sustained response and sustained total relief.

  1. Omeprazole promotes carcinogenesis of fore-stomach in mice with co-stimulation of nitrosamine.

    Science.gov (United States)

    Huang, Lei; Qi, Dong-Jiang; He, Wei; Xu, A-Man

    2017-09-19

    To investigate if oral omeprazole application induces cancers of fore and glandular stomach in mice. A total of 66 eligible male mice were randomly divided into 6 groups, which were treated with control reagent, low (6 mg/kg) and high dose omeprazole (30 mg/kg), N-methyl-N'-nitro-N-nitrosoguanidine (MNNG, 100 mg/L water), and MNNG plus low and high dose omeprazole, respectively. After 24 weeks, concentrations of acid phosphatase (ACP) and N-acetyl-β-D-glucosaminidase(NAG) in serum and spleen was examined, and p21 and mTOR levels in stomach were detected. The mouse spleen weight index was smaller in the omeprazole group than the control group, and in the MNNG plus omeprazole groups than the MNNG group. In the fore-stomach, more carcinomas were observed in the MNNG plus omeprazole groups than in the MNNG group. In the glandular stomach, there existed more atypical hyperplasia cases in the MNNG plus omeprazole groups than the MNNG-treated group, and one carcinoma was induced in the MNNG plus high dose omeprazole group. Omeprazole alone caused minor gastric pathological changes. Omeprazole treatment lowered both serum and spleen ACP and NAG levels in both the non-MNNG-treated and MNNG-treated subgroups. In fore-stomach, there existed decreased p21 and mTOR levels in the omeprazole-treated groups than in the control group, and in the MNNG plus omeprazole groups than the MNNG-treated group. Omeprazole promotes carcinogenesis of the mouse fore-stomach but not the glandular stomach following treatment with MNNG. Lysosomal hydrolase activity was inhibited and some cancer-associated proteins was dysregulated, which requires further explorations.

  2. Pharmacokinetics of omeprazole and its metabolites in three phases of menstrual cycle.

    Science.gov (United States)

    Nazir, Shabnam; Iqbal, Zafar; Ahmad, Lateef; Shah, Yasar; Nasir, Fazli

    2015-03-01

    Omeprazole (OMP) is effective in the treatment of gastric hyperacidity and is metabolized by CYP2C19 and CYP3A4. These enzymes are modulated by estrogen and progesterone which regulate the menstrual cycle. The variations in the pharmacokinetics (PK) of many drugs like amphetamine, benzodiazepines and caffeine have been reported during menstrual cycle. In present study, the PK of the omeprazole and its metabolites was investigated during various phases of the menstrual cycle. A single oral dose, open-label, non-controlled, pharmacokinetic study of omeprazole was conducted in healthy young/premenopausal females (n = 16). The PK of omeprazole, 5-hydroxy-omeprazole and omeprazole sulphone was evaluated in three phases of menstrual cycle. The blood samples were analyzed using reversed-phase HPLC coupled with UV detector and the PK data were evaluated. The activities of CYP2C19 and CYP3A4 were determined as AUC(OH-OMP)/AUC(OMP) and AUC(OMP-SUL)/AUC(OMP), respectively. Omeprazole showed significantly (p menstrual phases, respectively. The [Formula: see text] of 5-hydroxy omeprazole was also significantly (p < 0.05) higher in follicular phase. The metabolic ratios (MR) of 5-hydroxy omeprazole and omeprazole sulphone were lower in follicular phase compared with the luteal phase. The present study suggests that high estrogen levels of follicular phase may result in increased absorption of omeprazole. The lower MR for 5-hydroxy omeprazole and omeprazole sulphone in follicular phase as compared to luteal phase suggests that metabolism of omeprazole is low in follicular phase as compared to luteal phase, which is progesterone-dominant phase. However, the clinical significance for these findings needs to be determined.

  3. Low-dose intravenous heparin infusion in patients with aneurysmal subarachnoid hemorrhage: a preliminary assessment

    Science.gov (United States)

    Simard, J. Marc; Aldrich, E. Francois; Schreibman, David; James, Robert F.; Polifka, Adam; Beaty, Narlin

    2015-01-01

    Object Aneurysmal subarachnoid hemorrhage (aSAH) predisposes to delayed neurological deficits, including stroke and cognitive and neuropsychological abnormalities. Heparin is a pleiotropic drug that antagonizes many of the pathophysiological mechanisms implicated in secondary brain injury after aSAH. Methods The authors performed a retrospective analysis in 86 consecutive patients with Fisher Grade 3 aSAH due to rupture of a supratentorial aneurysm who presented within 36 hours and were treated by surgical clipping within 48 hours of their ictus. Forty-three patients were managed postoperatively with a low-dose intravenous heparin infusion (Maryland low-dose intravenous heparin infusion protocol: 8 U/kg/hr progressing over 36 hours to 10 U/kg/hr) beginning 12 hours after surgery and continuing until Day 14 after the ictus. Forty-three control patients received conventional subcutaneous heparin twice daily as deep vein thrombosis prophylaxis. Results Patients in the 2 groups were balanced in terms of baseline characteristics. In the heparin group, activated partial thromboplastin times were normal to mildly elevated; no clinically significant hemorrhages or instances of heparin-induced thrombocytopenia or deep vein thrombosis were encountered. In the control group, the incidence of clinical vasospasm requiring rescue therapy (induced hypertension, selective intraarterial verapamil, and angioplasty) was 20 (47%) of 43 patients, and 9 (21%) of 43 patients experienced a delayed infarct on CT scanning. In the heparin group, the incidence of clinical vasospasm requiring rescue therapy was 9% (4 of 43, p = 0.0002), and no patient suffered a delayed infarct (p = 0.003). Conclusions In patients with Fisher Grade 3 aSAH whose aneurysm is secured, postprocedure use of a low-dose intravenous heparin infusion may be safe and beneficial. PMID:24032706

  4. Effects of continuous infusion of etomidate at various dose rates on adrenal function in dogs.

    Science.gov (United States)

    Qin, Bangyong; Hu, Hongzhuan; Cao, Baofeng; Zhu, Zhaoqiong

    2016-01-08

    Etomidate is a commonly used sedative in intravenous anesthesia. The aim of this study was to compare the effects of various etomidate doses administered by continuous infusion on adrenal function in dogs under general anesthesia. Thirty-six healthy adult male dogs were randomly divided into six groups. Sodium pentobarbital alone was administered to the control group (group C); five experimental groups (E1, E2, E3, E4, and E5) were also given etomidate at doses of 10, 15, 20, 25, and 30 μg · kg(-1) · min(-1), respectively, to maintain anesthesia. Heart rate (HR), mean arterial pressure (MAP), and bispectral index (BIS) were monitored. Serum cortisol, aldosterone, adrenaline, and noradrenaline levels were measured, and HR, MAP, and BIS values recorded, before intubation (T0), and at 1 h, 2 h, and 3 h after intubation (T1-3). Cortisol and aldosterone levels in groups E1-5 decreased as the doses and times of continuous infusion of etomidate increased. The cortisol level was significantly decreased compared with baseline at T3 in group E1 and at T1-3 in groups E2-5 (P cortisol levels were significantly lower than T0 values at T3 in group E1 and at T1-3 in groups E2-5 (P cortisol levels at T2-3 in group E2 and at T1-3 in groups E3-5 compared with group C were also observed (P 0.05). Cortisol and aldosterone levels decreased with time and continuous infusion of etomidate; there were no significant changes in adrenaline and noradrenaline levels, HR, MAP, and BIS in any group.

  5. Rapid superselective high-dose cisplatin infusion with concomitant radiotherapy for hypopharyngeal cancer

    International Nuclear Information System (INIS)

    Homma, Akihiro; Oridate, Nobuhiko; Suzuki, Fumiyuki

    2010-01-01

    The survival and functional outcome for hypopharyngeal cancer (HPC) still remains poor despite aggressive standard treatment involving debilitating surgery and postoperative radiation therapy. We reviewed our experience in the management of advanced HPC using rapid superselective high-dose cisplatin infusion with concomitant radiotherapy (RADPLAT) as organ preservation therapy. Twenty-one previously untreated patients with HPC were given superselective intra-arterial infusions of cisplatin (100-120 mg/m 2 /week) with simultaneous intravenous infusion of thiosulfate to neutralize cisplatin toxicity and conventional external beam radiotherapy from 2000 through January, 2009. During the median follow-up period of 43 months, the 5-year overall survival and local control rate were 42.8% and 77.8%, respectively. All patients with N0-1 (n=10) are alive without disease so far. However, the 5-year overall survival of patients with N2b-3 (n=24) were 19%. It is not technically easy and sometimes dangerous to treat patients with HPC by intra-arterial chemotherapy. Recently, we consider that patients with T3-4a and N0-1, and primary tumor limited in one side are good candidate for RADPLAT. (author)

  6. Dynamics of Serum Pepsinogens on the Background of Double Standard Doses of Omeprazole in Patients with Gastroesophageal Reflux Disease and Functional Gastric Dyspepsia

    Directory of Open Access Journals (Sweden)

    S.G. Melashchenko

    2013-09-01

    Full Text Available In literature it has been reported that concentrations of serum pepsinogens increase during administration of proton pump inhibitors (PPI. However, the magnitude of these changes is still to be assessed. The aim of this study was to evaluate the changes in levels of pepsinogen I (PG-1 and pepsinogen II (PG-2 on the background of therapy with omeprazole which has been administered before breakfast in double standard dose (40 mg. The regimen of PPI administration completely corresponds to conventional PPI-test. There were two groups of patients: 1st one (gastroesophageal reflux desiase — 10 women and 9 men, mean age (52.37 ± 3.25 years; 2nd one (functional dyspepsia — 11 women and 8 men, mean age (48.37 ± 3.56 years. It was found that in 1st group PGI rises from (141.90 ± 7.99 mcg/l to (177.61 ± 7.81 mcg/l, in 2nd group — from (115.02 ± 10.16 mcg/l to (152.37 ± 12.33 mcg/l (p < 0.05. PG-2 level changes in the same. In 1st group PG-2 rises from (21.65 ± 3.13 mcg/l to (32.64 ± 3.42 mcg/l, in 2nd group — from (14.84 ± 1.64 mcg/l to (23.55 ± 2.37 mcg/l (p < 0.05. In 6 cases absolute increase of PGI (ΔPG-2 didn’t reach threshold of 7.0 mcg/l considered by us as level of insufficient acid inhibition. Two of these patients had atrophic gastritis (PG-1 < 50 mcg/l; ratio PG-/PG-2 < 3.0, rest 4 patients didn’t have atrophic gastritis but in half cases they hadn’t adequate answer to PPI administration. There was a significant correlation between increase of PG-1 level and disappearance of reflux complaints evaluated by dynamics in RS-cluster of GSRS-questionnaire.

  7. Hypertonic saline solution and high-dose furosemide infusion in cardiorenal syndrome: our experience

    Directory of Open Access Journals (Sweden)

    Francesco Ventrella

    2013-03-01

    Full Text Available Introduction Heart failure is frequently complicated by renal failure, and this association is a negative prognostic factor. These patients sometimes present oligo-/anuria and resistance to high-dose furosemide, a condition referred to as the cardiorenal syndrome (CRS. Acute or chronic reductions in left ventricular function result in decreased blood flow, with reduction of renal perfusion and activation of several neurohormonal systems, which cause resistance to diuretic therapy. This condition often requires ultrafiltration, which is an effective, but invasive and expensive procedure. Infusions of hypertonic saline solution (HSS and high-dose furosemide can be an effective alternative. Materials and methods From November 2009 through May 2010, our team treated 20 patients with CRS and resistance to iv boluses of high-dose furosemide. These patients were treated with small-volume (150-250 mL infusions of HSS (NaCl 1.57 – 4.5%, depending on serum Na values and high-dose furosemide twice a day. The aim of this treatment is to modify renal hemodynamics and the water-saline balance in the kidney by counteracting the extracellular fluid accumulation and eliminating symptoms of congestion. Results In 18 patients (90%, urine output was restored and renal function improved during the first hours of treatment. Clinical improvement was evident from the first day of therapy, and there were no adverse events. Two patients (10% did not respond to the treatment: one (who had been in critical condition since admission died; the other required regular sessions of ultrafiltration. Conclusions HSS combined with high-dose furosemide is a safe, effective, low-cost approach to the treatment of CRS that is resistant to diuretic therapy.

  8. Design and prospective validation of a dosing instrument for continuous infusion of vancomycin : a within-population approach

    NARCIS (Netherlands)

    van Maarseveen, Erik M.; Bouma, Annemien; Touw, Daniel J.; Neef, Cees; van Zanten, Arthur R.H.

    2014-01-01

    INTRODUCTION: The clinical application of continuous infusion (CoI) of vancomycin has gained interest in recent years. Since no international guidelines on initial dosing of vancomycin CoI exist, there is a need for methods to facilitate the switch from intermittent to continuous vancomycin dosing

  9. Omeprazole promotes proximal duodenal mucosal bicarbonate secretion in humans

    DEFF Research Database (Denmark)

    Mertz-Nielsen, A; Hillingsø, Jens; Bukhave, K

    1996-01-01

    The proton pump inhibitor, omeprazole, surprisingly resulted in higher rates of proximal duodenal mucosal bicarbonate secretion than previously reported using an H2 receptor antagonist for gastric acid inhibition. Gastroduodenal perfusions were performed in healthy volunteers to evaluate whether...... this incidental finding is explained by more potent gastric acid inhibition by omeprazole or might be caused by the different mode of drug action. Basal and stimulated gastric and duodenal bicarbonate secretion rates were measured in the same subjects in control experiments (n = 17) and after pretreatment...... with high dose omeprazole (n = 17) and ranitidine (n = 9), respectively, by use of a technique permitting simultaneous measurements. Concentrations of bicarbonate were measured in the respective effluents by the method of back titration. Both omeprazole and ranitidine completely inhibited gastric acid...

  10. Omeprazole promotes proximal duodenal mucosal bicarbonate secretion in humans

    DEFF Research Database (Denmark)

    Mertz-Nielsen, Anette; Hillingsø, J; Bukhave, Klaus

    1996-01-01

    The proton pump inhibitor, omeprazole, surprisingly resulted in higher rates of proximal duodenal mucosal bicarbonate secretion than previously reported using an H-2 receptor antagonist for gastric acid inhibition. Gastroduodenal perfusions were performed in healthy volunteers to evaluate whether...... this incidental finding is explained by more potent gastric acid inhibition by omeprazole or might be caused by the different mode of drug action. Basal and stimulated gastric and duodenal bicarbonate secretion rates were measured in the same subjects in control experiments (n=17) and after pretreatment with high...... dose omeprazole (n=17) and ranitidine (n=9), respectively, by use of a technique permitting simultaneous measurements. Concentrations of bicarbonate were measured in the respective effluents by the method of back titration. Both omeprazole and ranitidine completely inhibited gastric acid secretion (p...

  11. Early effect of oral administration of omeprazole with mosapride as compared with those of omeprazole alone on the intragastric pH

    Directory of Open Access Journals (Sweden)

    Iida Hiroshi

    2012-03-01

    Full Text Available Abstract Background The ideal medication for acid-related diseases should have a rapid onset of action to promote hemostasis and cause efficient resolution of symptoms. The aim of our study was to comparatively investigate the inhibitory effect on gastric acid secretion of a single oral administration of omeprazole plus mosapride with that of omeprazole alone. Methods Ten Helicobacter pylori-negative male subjects participated in this randomized, two-way crossover study. Intragastric pH was monitored continuously for 6 hours after a single oral administration of omeprazole 20 mg or that of omeprazole 20 mg plus mosapride 5 mg (the omeprazole being administered one hour after the mosapride. Each administration was separated by a 7-days washout period. Results The average pH during the 6-hour period after administration of omeprazole 20 mg plus mosapride 5 mg was higher than that after administration of omeprazole 20 mg alone (median: 3.22 versus 4.21, respectively; p = 0.0247. Conclusions In H. pylori -negative healthy male subjects, an oral dose of omeprazole 20 mg plus mosapride 5 mg increased the intragastric pH more rapidly than omeprazole 20 mg alone.

  12. [EEG-adjusted target-controlled infusion : Propofol target concentration with different doses of remifentanil].

    Science.gov (United States)

    Büttner, N; Schultz, B; Grouven, U; Schultz, A

    2010-02-01

    The aim of this study was to examine to what extent the use of electroencephalography (EEG) monitoring leads to an adaptation of the target-controlled infusion (TCI) concentration of propofol during propofol anaesthesia with different doses of remifentanil. With ethics committee approval 60 patients (27-69 years old) with American Society of Anesthesiologists classification (ASA) I-III received anaesthestics with propofol (TCI, Diprifusor, AstraZeneca, Wedel, Deutschland) and 0.2, 0.4, or 0.6 microg/kg body weight remifentanil, respectively (groups 1-3). Anaesthesia was maintained at a level of deep hypnosis (EEG stages D(2)/E(0), EEG monitor: Narcotrend, version 2.0/5.0, manufacturer: MT MonitorTechnik, Bad Bramstedt, Germany). During the steady state the propofol concentration in groups 1-3 was 3.02+/-0.86, 1.93+/-0.53 and 1.60+/-0.55 microg/ml, respectively (p<0.001). Women had a higher propofol consumption than men (p<0.05). Dreams during anaesthesia were more often reported by women than by men (p<0.05). The need for postoperative analgesia decreased with an increasing intraoperative remifentanil dose (p<0.05). The study demonstrates that remifentanil has both analgetic and hypnotic effects. With increasing remifentanil dose the propofol requirement decreased and in this context EEG monitoring is useful to adapt the target concentrations of propofol to the patients' age and gender.

  13. Direct intratumoral infusion of liposome encapsulated rhenium radionuclides for cancer therapy: Effects of nonuniform intratumoral dose distribution

    International Nuclear Information System (INIS)

    Hrycushko, Brian A.; Li Shihong; Goins, Beth; Otto, Randal A.; Bao, Ande

    2011-01-01

    Purpose: Focused radiation therapy by direct intratumoral infusion of lipid nanoparticle (liposome)-carried beta-emitting radionuclides has shown promising results in animal model studies; however, little is known about the impact the intratumoral liposomal radionuclide distribution may have on tumor control. The primary objective of this work was to investigate the effects the intratumoral absorbed dose distributions from this cancer therapy modality have on tumor control and treatment planning by combining dosimetric and radiobiological modeling with in vivo imaging data. Methods: 99m Tc-encapsulated liposomes were intratumorally infused with a single injection location to human head and neck squamous cell carcinoma xenografts in nude rats. High resolution in vivo planar imaging was performed at various time points for quantifying intratumoral retention following infusion. The intratumoral liposomal radioactivity distribution was obtained from 1 mm resolution pinhole collimator SPECT imaging coregistered with CT imaging of excised tumors at 20 h postinfusion. Coregistered images were used for intratumoral dosimetric and radiobiological modeling at a voxel level following extrapolation to the therapeutic analogs, 186 Re/ 188 Re liposomes. Effective uniform dose (EUD) and tumor control probability (TCP) were used to assess therapy effectiveness and possible methods of improving upon tumor control with this radiation therapy modality. Results: Dosimetric analysis showed that average tumor absorbed doses of 8.6 Gy/MBq (318.2 Gy/mCi) and 5.7 Gy/MBq (209.1 Gy/mCi) could be delivered with this protocol of radiation delivery for 186 Re/ 188 Re liposomes, respectively, and 37-92 MBq (1-2.5 mCi)/g tumor administered activity; however, large intratumoral absorbed dose heterogeneity, as seen in dose-volume histograms, resulted in insignificant values of EUD and TCP for achieving tumor control. It is indicated that the use of liposomes encapsulating radionuclides with higher

  14. Deleterious Effects of High Dose Connexin 43 Mimetic Peptide Infusion After Cerebral Ischaemia in Near-Term Fetal Sheep

    Directory of Open Access Journals (Sweden)

    Alistair J. Gunn

    2012-05-01

    Full Text Available Hypoxic-ischaemic brain injury at birth is associated with 1–3/1000 cases of moderate to severe encephalopathy. Previously, we have shown that connexin 43 hemichannel blockade, with a specific mimetic peptide, reduced the occurrence of seizures, improved recovery of EEG power and sleep state cycling, and improved cell survival following global cerebral ischaemia. In the present study, we examined the dose response for intracerebroventricular mimetic peptide infusion (50 µmol/kg/h for 1 h, followed by 50 µmol/kg/24 h (low dose or 50 µmol/kg/h for 25 h (high dose or vehicle only (control group, starting 90 min after the end of ischaemia, following global cerebral ischaemia, induced by 30 min bilateral carotid artery occlusion, in near-term fetal sheep (128 ± 1 days gestation. Both peptide infusion groups were associated with a transient significant increase in EEG power between 2–12 h after ischaemia. The ischaemia-low dose group showed a significant recovery of EEG power from day five compared to the ischaemia-vehicle and -high dose groups. In contrast, the high dose infusion was associated with greater secondary increase in impedance (brain cell swelling, as well as a trend towards a greater increase in lactate concentration and mortality. These data suggest that higher doses of connexin mimetic peptide are not beneficial and may be associated with adverse outcomes, most likely attributable to uncoupling of connexin 43 gap junctions leading to dysfunction of the astrocytic syncytium.

  15. The effect of low-dose oxytocin infusion on cerebral hemodynamics in pregnant women.

    Science.gov (United States)

    van Veen, Teelkien R; Belfort, Michael A; Zeeman, Gerda G

    2011-08-01

    We investigated the cerebrovascular effects of continuous infusion of low-dose oxytocin in normal pregnant women undergoing induction of labor. In our prospective observational study, middle cerebral artery velocity was measured with transcranial Doppler ultrasound in 25 healthy, normotensive, nonsmoking patients undergoing induction of labor. No vasoactive drugs were used before or during the study period. Measurements were made at baseline and 15, 30, 60, and 120 minutes after oxytocin initiation. Mean arterial pressure, cerebral perfusion pressure, resistance index, resistance area product, and cerebral flow index at different times were calculated and compared using one-way analysis of variance (ANOVA) for repeated measures or Friedman repeated-measures ANOVA as appropriate, with P<0.05 regarded as significant. No significant systemic or cerebrovascular changes were noted after oxytocin initiation, and there was no correlation between the dosage administered and any hemodynamic parameter. Induction-dose oxytocin does not significantly affect selected cerebral hemodynamic parameters in the first 2 hours after initiation. © Thieme Medical Publishers.

  16. Dose-response and concentration-response relation of rocuronium infusion during propofol nitrous oxide and isoflurane nitrous oxide anaesthesia

    NARCIS (Netherlands)

    Kansanaho, M; Olkkola, KT; Wierda, JMKH

    The dose-response and concentration-response relation of rocuronium infusion was studied in 20 adult surgical patients during proporfol-nitrous oxide and isoflurane (1 MAC) -nitrous oxide anaesthesia. Neuromuscular block was kept constant, initially at 90% and then at 50% with a closed-loop feedback

  17. Amino acid infusions induce reversible, dose-related decreases in bile flow in the isolated rat liver.

    Science.gov (United States)

    Shattuck, K E; Grinnell, C D; Rassin, D K

    1993-01-01

    Parenteral infusion of amino acid solutions is known to produce cholestasis in experimental animal models and in the isolated perfused rat liver. To characterize the dose responsiveness and reversibility of amino acid-induced cholestasis, isolated rat livers were perfused with solutions containing 1.5, 3.0, or 6.0 g of amino acids for 1 hour and allowed to recover for 30 minutes. Perfusion of livers resulted in a rapid, dose-related decrease in bile flow (p < .0001 at doses of 3.0 and 6.0 g). When the amino acid solution was discontinued, bile flow recovered to near control rates. Infusion of taurocholate reduced the magnitude of the decrease in bile flow associated with amino acid infusion but did not prevent it. Infusion of amino acid solutions was associated with the following changes in bile: (1) dose-related increases in total free amino acid concentrations; (2) increased osmolarity; (3) increased glucose concentrations; (4) increased potassium concentrations; (5) decreased chloride concentrations; (6) increased oxygen uptake in livers not perfused with added taurocholate; and (7) increased total bile acid concentrations in livers perfused with added taurocholate. Additional investigations are needed to determine whether these associations are attributable to individual amino acids or the total metabolic load of the amino acids.

  18. A NEW ANIMAL-MODEL FOR HUMAN PREECLAMPSIA - ULTRA-LOW-DOSE ENDOTOXIN INFUSION IN PREGNANT RATS

    NARCIS (Netherlands)

    FAAS, MM; SCHUILING, GA; BALLER, JFW; VISSCHER, CA; BAKKER, WW

    OBJECTIVE: An animal model for preeclampsia was developed by means of an ultra-low-dose endotoxin infusion protocol in conscious pregnant rats. STUDY DESIGN: Rats received a permanent jugular vein cannula on day 0 of pregnancy, through which endotoxin (1.0 mu/kg body weight) (n = 10) or saline

  19. Effect of short-term intralipid infusion on the immune response during low-dose endotoxemia in humans

    DEFF Research Database (Denmark)

    Krogh-Madsen, R.; Plomgaard, P.; Åkerström, Thorbjörn

    2008-01-01

    on the inflammatory response to a low dose of endotoxin. Fourteen healthy male volunteers underwent the following two trials in a randomized crossover design: 1) continuous infusion of 20% Intralipid [0.7 ml.kg(-1).h(-1) (1.54 g/kg)] for 11 h, and 2) infusion of isotonic saline for 11 h (control). In each trial......, heparin was given to activate lipoprotein lipase, and an intravenous bolus of endotoxin (0.1 ng/kg) was given after 6 h of Intralipid/saline infusion. Blood samples and muscle and fat biopsies were obtained before the Intralipid/saline infusion and before as well as after infusion of an endotoxin bolus....... Plasma levels of FFA, triglycerides, and glycerol were markedly increased during the Intralipid infusion. Endotoxin exposure induced an increase in plasma levels of TNF-alpha, IL-6, and neutrophils and further stimulated gene expression of TNF-alpha and IL-6 in both skeletal muscle and adipose tissue...

  20. Effect of omeprazole and cimetidine on healing of chronic gastric ulcers and gastric acid secretion in rats

    DEFF Research Database (Denmark)

    Poulsen, Steen Seier

    1988-01-01

    The effect of omeprazole and cimetidine on healing of chronic gastric ulcers and gastric acid secretion was investigated in rats. The effect of three doses of omeprazole given orally once daily for 25 days was investigated. In controls median ulcer healing was 19.6% after 25 days. Omeprazole...... increased median ulcer healing from 36% at 145 mumole/kg/day to 80% at 580 mumole/kg/day. Basal and pentagastrin stimulated gastric acid secretion decreased dose-dependently by nearly 90% at a dose of 580 mumole/kg/day 22-24 hr after the last dose of omeprazole. Cimetidine given twice daily, in a dose...... that initially inhibits gastric acid secretion by 95%, reduced acid secretion by only 50% 11 hr after the last dose. Median ulcer healing after treatment with cimetidine for 25 days was 41%. This study demonstrates that omeprazole has a more long-acting inhibitory effect on gastric acid secretion compared...

  1. Efficacy of different doses of sugammadex after continuous infusion of rocuronium.

    Science.gov (United States)

    Soto Mesa, Diego; Fayad Fayad, Mounir; Pérez Arviza, Laura; Del Valle Ruiz, Verónica; Cosío Carreño, Fernando; Arguelles Tamargo, Luis; Amorín Díaz, Manuel; Fernández-Pello Montes, Sergio

    2015-04-16

    To evaluate the effects of two different doses of sugammadex after maintenance anesthesia with sevofluorane and remifentanil and deep rocuronium-induced neuromuscular blockade (NMB). Patients between 20 and 65 years of age, with American Society of Anesthesiologists physical status classification I-II, undergoing gynecological surgery were included in a prospective, comparative and randomized study. NMB was induced with an injection of 0.6 mg/kg of rocuronium followed by continuous infusion of 0.3-0.6 mg/kg per hour to maintain a deep block. Anesthesia was maintained with sevofluorane and remifentanil. Finally, when surgery was finished, a bolus of 2 mg/kg (group A) or 4 mg/kg (group B) of sugammadex was applied when the NMB first response in the train-of-four was reached. The primary clinical endpoint was time to recovery to a train-of-four ratio of 0.9. Other variables recorded were the time until recovery of train-of-four ratio of 0.7, 0.8, hemodynamic variables (arterial blood pressure and heart rate at baseline, starting sugammadex, and minutes 2, 5 and 10) and adverse events were presented after one hour in the post-anesthesia care unit. Thirty-two patients were included in the study: 16 patients in group A and 16 patients in group B. Only 14 patients each group were recorded because arterial pressure values were lost in two patients from each group in minute 10. The two groups were comparable. Median recovery time from starting of sugammadex administration to a train-of-four ratio of 0.9 in group A and B was 129 and 110 s, respectively. The estimated difference in recovery time between groups was 24 s (95%CI: 0 to 45 s, Hodges-Lehmann estimator), entirely within the predefined equivalence interval. Times to recovery to train-of-four ratios of 0.8 (group A: 101 s; group B: 82.5 s) and 0.7 (group A: 90 s; group B: 65 s) from start of sugammadex administration were not equivalent between groups. There was not a significant variation in the arterial pressure

  2. The effect of omeprazole treatment on the gut microflora and neutrophil function.

    Science.gov (United States)

    Kostrzewska, Maja; Świdnicka-Siergiejko, Agnieszka; Olszańska, Dorota; Jurkowska, Grażyna; Garley, Marzena; Ratajczak-Wrona, Wioletta; Jabłońska, Ewa; Jamiołkowski, Jacek; Dabrowski, Andrzej

    2017-10-01

    Proton pump inhibitors (PPIs) may increase the risk of Clostridium difficile infections. There are interactions between gut microbiota and innate immune cells including neutrophils. We evaluated the effect of treatment with omeprazole on the gut microflora and neutrophil function. In 50 patients, we evaluated the effect of 4-week omeprazole treatment (n=25 with 20mg per day and n=25 with 20mg twice daily) on intragastric pH, results of stool culture and lactulose hydrogen breath test (LHBT) and neutrophil function. The treatment caused significant increase of the mean intragastric pH, especially in the group with 20mg omeprazole twice daily (from 2.05±0.59 to 5.06±1.6, P<0.001). In LHBT, the increase of hydrogen concentration was observed in higher percentage of patients with 20mg of omeprazole twice daily, compared to patients with the lower dose (42.1% vs 29.4%; ns). Four weeks of omeprazole treatment have caused considerable changes in stool culture results. Patients treated with higher dose of omeprazole have had some tendency to decrease diversity of colonic microflora in comparison with patients treated with the lower dose of omeprazole. Treatment with omeprazole did not result in C. difficile positive stool culture and had no significant effect on neutrophil function. Omeprazole treatment have caused considerable changes in stool culture results. Patients treated with the higher dose had some tendency to decreased diversity of colonic microflora and towards changes in fermenting bacteria of the gut. The potential effect of omeprazole on gut microflora does not depend on neutrophil function deterioration. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  3. Low efficacy of an ultra-short term, once-daily dose triple therapy with omeprazole, azithromycin, and secnidazole for Helicobacter pylori eradication in peptic ulcer Baixa eficácia de um tratamento tríplice de curta duração, em dose única diária, para erradicação do Helicobacter pylori em pacientes ulcerosos com Omeprazol, Azitromicina e Secnidazol

    Directory of Open Access Journals (Sweden)

    Fernando Marcuz Silva

    2002-02-01

    Full Text Available PURPOSE: To determine the eradication rate of an ultra-short treatment schedule for Helicobacter pylori infection in a population with peptic ulcers, using omeprazole, secnidazole, and azithromycin in a once-daily dose for 3 days. METHODS: Thirty patients with peptic ulcer diagnosed by upper endoscopy and for Helicobacter pylori infection by rapid urease test and histologic examination received omeprazole 40 mg, secnidazole 1000 mg, and azithromycin 500 mg, administered once daily for 3 days. A follow-up exam was performed 12 weeks after the end of the treatment. Patients who were negative for Helicobacter pylori infection by rapid urease test and histologic examination were considered cured. RESULTS: Patients were predominantly female, and the mean age was 50 years. Duodenal peptic ulcer was found in 73% of the patients. Eradication was achieved in 9 of the 28 (32% patients as determined from the follow-up endoscopic exam. The eradication rate by intention to treat was 30%. Side effects were present in 3% of the patients, and compliance to treatment was total. CONCLUSIONS: In spite of the low rate of side effects and good compliance, the eradication index was low. A possible drawback of this therapy is that it reduces the efficacy of macrolide and nitroimidazole compounds in subsequent treatments.OBJETIVO: Testar a eficácia de um esquema ultra-curto de erradicação do H. pylori em uma população de ulcerosos, usando Omeprazol, Secnidazol e Azitromicina em dose única diária por três dias. PACIENTES E MÉTODOS: Trinta doentes portadores de úlcera péptica, documentada por exame endoscópico e com infecção pelo H. pylori confirmada pelo teste da urease e exame histológico, foram tratados com Omeprazol 40mg, Secnidazol 1000 mg e Azitromicina 500mg dados em dose única diária por três dias. Em controle endoscópico realizado 12 semanas após o término do tratamento, foram considerados curados da infecção os pacientes que apresentaram

  4. Doubling the single-dose infusion rate of tocilizumab in rheumatoid arthritis is safe and efficacious

    DEFF Research Database (Denmark)

    Lindegaard, H M; Johansen, P; Gröndal, G

    2016-01-01

    OBJECTIVES: To investigate the impact of enhanced infusion rate of tocilizumab on the occurrence of infusion reactions, overall safety, and efficacy in rheumatoid arthritis (RA). METHOD: We conducted a 24-week multicentre, open-label, randomized parallel group study comparing adverse event (AE......) and effect profiles following tocilizumab IV 8 mg/kg every 4 weeks over 31 min vs. standard 60-min infusions in patients with RA and an inadequate clinical response to disease-modifying anti-rheumatic drugs (DMARDs) and/or tumour necrosis factor (TNF)-α inhibitors. RESULTS: A total of 47 patients were...... enrolled in the study and randomized to fast infusions (n = 25) and controls (n = 22). Incidences of infusion reactions were similar between the two groups, neither of them leading to withdrawal. Likewise, the incidence of additional AEs did not differ between the treatment arms. Two serious adverse events...

  5. Intra-arterial infusion of MTX for the treatment of cesarean scar pregnancy: a comparative study between different doses

    International Nuclear Information System (INIS)

    Gu Weijin; Wang Haiyun; Wan Jun; Zhang Lei; Wang Ying; Wang Wei; Ji Fang; Ji Lihua

    2010-01-01

    Objective: To investigate the effective dose of methotrexate (MTX) via intra-arterial infusion for the treatment of cesarean scar pregnancy. Methods: Thirty-six cases of incisional scar pregnancy at the gestational age of 5-9 weeks received bilateral uterine arterial infusion of MTX. According to the dose of MTX used, the patients were randomly and equally divided into four groups with MTX dose of 60, 100, 150 and 200 mg respectively. After the perfusion was completed the embolization of both uterine arteries with Gelfoam was carried out until the uterine arteries were no longer visualized on DSA. Uterine curettage was conducted within 1-7 days after the treatment. Results: In one week after the procedure, the difference in the decreasing rate of serum β-HCG and progesterone between group 60 mg and group 200 mg was of statistical significance (P 0.05). The hospitalization days of group 60 mg was the longest, while that of group 200 mg was the shortest. Conclusion: The recommended dose of MTX used via intra-arterial infusion in treating cesarean scar pregnancy is 200 mg. The interventional procedure can kill the embryo tissue and quickly lower the serum β-HCG and progesterone levels,it can also shorten the patient's hospitalization time. (authors)

  6. Compound list: omeprazole [Open TG-GATEs

    Lifescience Database Archive (English)

    Full Text Available omeprazole OPZ 00012 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in_vitro/omeprazole....Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vitro/omeprazole....Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Single/omeprazole...ive/open-tggates/LATEST/Rat/in_vivo/Liver/Repeat/omeprazole.Rat.in_vivo.Liver.Repeat.zip ftp://ftp.bioscienc...edbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Kidney/Single/omeprazole.Rat.in_vivo.Kidney.Single.zip ftp:/

  7. The effect of intravenous omeprazole on the gastric and duodenal potential difference and pH in healthy subjects

    DEFF Research Database (Denmark)

    Rubinstein, E; Højgaard, L

    1993-01-01

    The effect of intravenous omeprazole (40 and 80 mg) on the gastric and duodenal potential difference (PD) and pH was investigated in 9 healthy volunteers. Gastric PD and pH increased significantly (p omeprazole, and the increases were equal following the two doses. No changes were...... found in duodenal PD or pH. It has been claimed that gastric PD changes following acid secretion inhibition with cimetidine and glucagon might be due to changes in the parietal cell surface area. Omeprazole causes no changes in the parietal cell structure, and the changes in gastric PD following...... omeprazole might therefore be ascribed to changes in mucosal electrophysiologic transport or resistance....

  8. Donor leukocyte infusions in relapsed Hodgkin's lymphoma following allogeneic stem cell transplantation: CD3+ cell dose, GVHD and disease response.

    Science.gov (United States)

    Anderlini, P; Acholonu, S A; Okoroji, G-J; Andersson, B S; Couriel, D R; De Lima, M J; Donato, M L; Khouri, I F; Giralt, S A; Ueno, N T; Champlin, R E

    2004-09-01

    Nine patients with advanced Hodgkin's lymphoma (HL) who had undergone allogeneic stem cell transplantation (allo-SCT) received donor leukocyte infusions (DLIs) for treatment of persistent or progressive disease (PD). A total of 15 DLIs were performed, with four patients receiving more than one DLI. In four patients, prior salvage chemotherapy was administered. The median CD3+ cell dose administered was 77.5 x 10(6)/kg (range 5-285). GVHD developed in all but one patient. The response rate was 4/9 (44%). Three of these four responders developed GVHD and 3/4 had received chemotherapy. No correlation was observed between CD3+ cell dose infused and disease response. At the latest follow-up, three patients are alive and six have expired (PD n=3, nonrelapse mortality n=3). The median response duration was 7 months (range 4-9), with one response currently ongoing. These data suggest that DLIs for immunotherapy of recurrent HL have significant activity, although they frequently leads to GVHD. The small sample size does not allow any conclusion as to whether chemotherapy administration increases the chance of response. The CD3 cell dose infused does not seem to correlate with disease response.

  9. Low-dose ketamine infusion for labor analgesia: A double-blind, randomized, placebo controlled clinical trial

    Directory of Open Access Journals (Sweden)

    Sam Joel

    2014-01-01

    Full Text Available Background: Most primary and secondary level hospitals in developing countries provide inadequate labor analgesia due to various medical, technical and economic reasons. This clinical trial was an effort to study the efficacy, safety and feasibility of intravenous (IV ketamine to provide labor analgesia. Materials and Methods: A total of 70 parturients were consented and randomly assigned to receive either IV ketamine or 0.9% saline. A loading dose of ketamine (0.2 mg/kg was followed-by an infusion (0.2 mg/kg/h until the delivery of the neonate. Similar volume of saline was infused in the placebo-group. Intramuscular meperidine was the rescue analgesic in both groups. The pain score, hemodynamic parameters of mother and fetus and the anticipated side-effects of ketamine were observed for. The newborn was assessed by the Neonatologist. Results: The pain score showed a decreasing trend in the ketamine group and after the 1 st h more than 60% of women in the ketamine group had pain relief, which was statistically significant. There was no significant clinical change in the maternal hemodynamics and fetal heart rate. However, 17 (48.5% of them had transient light headedness in the ketamine group. All the neonates were breast fed and the umbilical cord blood pH was between 7.1 and 7.2. The overall satisfaction was significantly high in the intervention group (P = 0.028. Conclusion: A low-dose ketamine infusion (loading dose of 0.2 mg/kg delivered over 30 min, followed-by an infusion at 0.2 mg/kg/h could provide acceptable analgesia during labor and delivery.

  10. Dose-dependent changes in neuroinflammatory and arachidonic acid cascade markers with synaptic marker loss in rat lipopolysaccharide infusion model of neuroinflammation

    Directory of Open Access Journals (Sweden)

    Kellom Matthew

    2012-05-01

    Full Text Available Abstract Background Neuroinflammation, caused by six days of intracerebroventricular infusion of bacterial lipopolysaccharide (LPS, stimulates rat brain arachidonic acid (AA metabolism. The molecular changes associated with increased AA metabolism are not clear. We examined effects of a six-day infusion of a low-dose (0.5 ng/h and a high-dose (250 ng/h of LPS on neuroinflammatory, AA cascade, and pre- and post-synaptic markers in rat brain. We used artificial cerebrospinal fluid-infused brains as controls. Results Infusion of low- or high-dose LPS increased brain protein levels of TNFα, and iNOS, without significantly changing GFAP. High-dose LPS infusion upregulated brain protein and mRNA levels of AA cascade markers (cytosolic cPLA2-IVA, secretory sPLA2-V, cyclooxygenase-2 and 5-lipoxygenase, and of transcription factor NF-κB p50 DNA binding activity. Both LPS doses increased cPLA2 and p38 mitogen-activated protein kinase levels, while reducing protein levels of the pre-synaptic marker, synaptophysin. Post-synaptic markers drebrin and PSD95 protein levels were decreased with high- but not low-dose LPS. Conclusions Chronic LPS infusion has differential effects, depending on dose, on inflammatory, AA and synaptic markers in rat brain. Neuroinflammation associated with upregulated brain AA metabolism can lead to synaptic dysfunction.

  11. A randomized trial of phenylephrine infusion versus bolus dosing for nausea and vomiting during Cesarean delivery in obese women.

    Science.gov (United States)

    George, Ronald B; McKeen, Dolores M; Dominguez, Jennifer E; Allen, Terrence K; Doyle, Patricia A; Habib, Ashraf S

    2018-03-01

    Hypotension is common after spinal anesthesia for Cesarean delivery. It is associated with nausea, vomiting, and fetal acidosis. Previous research on phenylephrine excluded obese subjects. We compared the incidence of intraoperative nausea and vomiting (IONV) in obese patients who received a prophylactic phenylephrine infusion vs those who received bolus dosing for the treatment of spinal-induced hypotension. In this multicentre, double-blinded randomized controlled trial, 160 obese women undergoing elective Cesarean delivery under spinal anesthesia were randomized to receive a prophylactic phenylephrine infusion initiated at 50 μg·min -1 (and titrated according to a predefined algorithm) or 100 μg phenylephrine boluses to treat hypotension. Maternal systolic blood pressure was maintained within 20% of baseline. The primary study outcome was the incidence of IONV. Intraoperative nausea and vomiting were significantly reduced in the infusion group compared to the bolus group (46% vs 75%, respectively; relative risk [RR], 0.61; 95% confidence interval [CI], 0.47 to 0.80; P < 0.001). This was associated with significantly reduced need for intraoperative rescue antiemetics (26% vs 42%, respectively; RR, 0.62; 95% CI, 0.40 to 0.97; P = 0.04), but no difference in the incidence of vomiting. Postoperative vomiting at two hours was reduced in the infusion group (11% vs 25%; RR, 0.44; 95% CI, 0.21 to 0.90; P = 0.02);however, there were no differences in the incidence or severity of postoperative nausea, need for rescue antiemetics at two hours and 24 hr, or the incidence of postoperative vomiting at 24 hr. In obese women undergoing Cesarean delivery with spinal anesthesia, prophylactic phenylephrine infusion was associated with less intraoperative nausea, less need for rescue antiemetics, and reduced early postoperative vomiting. www.clinicaltrials.gov (NCT01481740). Registered 22 July 2011.

  12. Ventricular fibrillation in a 5-year-old child on therapeutic dose of quinine dihydrochloride infusion for acute malaria.

    Science.gov (United States)

    Busari, Olusegun; Busari, Olusogo

    2008-08-01

    Malaria is no doubt a disease of public health significance in the tropics. Plasmodium falciparum, resistant to the majority of the first-line antimalarial drugs, now causes most of the infections treated in sub-Saharan Africa. Although there is increasing use of artemisinin-based combination therapy in many African nations, quinine still remains a commonly used drug for severe and chloroquine-resistant malaria. Cardiotoxicity associated with quinine has been largely reported. However, this was often more common with toxic doses. This case report is on a 5-year-old African Nigerian who was undergoing treatment for uncomplicated malaria with quinine dihydrochloride infusion. All the laboratory investigations done were within normal limits except for positive blood films for malarial parasites. However, pretreatment electrocardiographic evaluation of the patient was not carried out. She developed ventricular fibrillation and died quinine infusion.

  13. Phase-I dose escalation and sequencing study of docetaxel and continuous infusion topotecan in patients with advanced malignancies.

    Science.gov (United States)

    Posey, James A; Wang, Hui; Hamilton, Joelle; Delgrosso, Alma; Zhang, Ruiwen; Freda, Timothy; Zamboni, William C

    2005-08-01

    Anti-tumor activity can often be enhanced with combination therapy in managing patients with metastatic cancer. However, dose sequence and schedule of delivery can alter the pharmacokinetics, toxicity, and anti-tumor response. Therefore, attention to drug-drug interactions which may be sequence or schedule-dependent are necessary. Docetaxel and topotecan are non-cross-resistance cytotoxic agents with activity in a variety of malignancies. The goal of this study was to determine the maximum tolerated dose of docetaxel and continuous infusion topotecan using two sequences of administration. Patients were randomized to schedule A or B and enrolled in four escalating-dose cohorts. On schedule A, docetaxel was administered over 1 h and followed by topotecan administered over 72 h. On schedule B, topotecan was given as a 72 h continuous infusion followed by a 1 h infusion of docetaxel. While the doses for the docetaxel and topotecan were the same for schedule A and schedule B, the toxicities, and thus the determination of maximum tolerated dose (MTD), were assessed independently. The plasma pharmacokinetic disposition of topotecan and docetaxel were evaluated during the first cycle of each sequence to assess drug interactions. Thirty patients, 20 males and 10 females were evaluable for toxicity and response. Four patients were chemonaive. Mean number cycles given were 3. Grade 3/4 thrombocytopenia and neutropenia were comparable on both schedules, as was the dose-limiting toxicity (DLT) for both schedules. There were no apparent differences in absolute neutrophil count or platelet nadirs between schedules A and B for three of the four cohorts. The principal non-hematologic toxicity was nausea and vomiting. The time of overlap of topotecan lactone or total concentrations and docetaxel concentrations were greater on schedule A as compared with schedule B and was associated with reduced clearance of docetaxel on schedule A as compared to schedule B. However, the mean

  14. Acid Inhibitory Effect of a Combination of Omeprazole and Sodium Bicarbonate (CDFR0209) Compared With Delayed-Release Omeprazole 40 mg Alone in Healthy Adult Male Subjects.

    Science.gov (United States)

    Kim, Kyu-Nam; Yang, Sung-Won; Kim, Hyunil; Kwak, Seong Shin; Kim, Young-Sang; Cho, Doo-Yeoun

    2018-01-01

    CDFR0209, a combination of an immediate-release formulation of omeprazole 40 mg and sodium bicarbonate 1100 mg, has been developed to treat acid-related disorders. We compared the acid inhibitory effects of CDFR0209 and delayed-release omeprazole (omeprazole-DR, Losec 40 mg) after repeated dosing in Helicobacter pylori-negative healthy adult male subjects. In this 2-period crossover study, 30 subjects were randomized to CDFR0209 or omeprazole-DR daily for 7 days. An ambulatory continuous 24-hour intragastric pH recording was performed at baseline and on days 1 and 7 of each administration period. Integrated gastric acidity was calculated from time-weighted average hydrogen ion concentrations at each hour of the 24-hour record. An analysis of variance model was used to test the pharmacodynamic equivalence of CDFR0209 and omeprazole-DR, using the natural logarithmic transformation of the percent decrease from baseline in integrated gastric acidity for the 24-hour interval after the seventh dose of each omeprazole formulation. The geometric least-squares mean ratios (CDFR0209/omeprazole-DR) of the percent decrease from baseline in integrated gastric acidity was 0.98 (90%CI, 0.93-1.07). Both CDFR0209 and omeprazole-DR are equally effective in decreasing integrated gastric acidity at steady state. © 2017, The American College of Clinical Pharmacology.

  15. Prediction of boron concentration in blood from low dose infusion for the patients of BNCT at JAERI

    International Nuclear Information System (INIS)

    Shibata, Y.; Matsumura, A.; Yamamoto, T.

    2000-01-01

    It is difficult to measure boron concentration in blood during neutron irradiation in BNCT. We have investigated the predictability of boron concentration in blood from the data at 1st craniotomy after low dose BSH infusion. Two patients entered BNCT at JRR2 in 1995/1996, and 5 patients entered BNCT at JRR4 in 1992/2000. The patients include 2 male and 5 female and their age ranged from 20 to 66. In 5 patients 1 g of BSH was infused before 1st tumor removal operation and boron concentrations in blood were examined around this operation. All patients were infused 100 mg/kg of BSH at 12 hours prior to BNCT and boron concentrations were examined before and after BNCT using prompt gamma ray analysis or ICP-AES. Each results showed biphasic pharmacokinetic profile. Personal variations of the pharmacokinetics of BSH were small. Final and 1 g data were well correlated and final boron concentrations at BNCT were predictable from 1 g studies. (author)

  16. Renal tubular reabsorption of sodium and water during infusion of low-dose dopamine in normal man

    DEFF Research Database (Denmark)

    Olsen, Niels Vidiendal; Hansen, J M; Ladefoged, S D

    1990-01-01

    of sodium and water during dopamine infusion (3 micrograms min-1 kg-1) were estimated in 12 normal volunteers. 2. CNa increased by 128% (P less than 0.001). Effective renal plasma flow and GFR increased by 43% (P less than 0.001) and 9% (P less than 0.01), respectively. CLi increased in all subjects by......, on average, 44% (P less than 0.001). Fractional proximal reabsorption [1-(CLi/GFR)] decreased by 13% after dopamine infusion (P less than 0.001), and estimated absolute proximal reabsorption rate (GFR-CLi) decreased by 8% (P less than 0.01). Absolute distal sodium reabsorption rate [(CLi-CNa) x PNa, where...... PNa is plasma sodium concentration] increased (P less than 0.001), and fractional distal sodium reabsorption [(CLi-CNa)/CLi] decreased (P less than 0.001). 3. It is concluded that natriuresis during low-dose dopamine infusion is caused by an increased outflow of sodium from the proximal tubules...

  17. Prediction of boron concentration in blood from low dose infusion for the patients of BNCT at JAERI

    Energy Technology Data Exchange (ETDEWEB)

    Shibata, Y.; Matsumura, A.; Yamamoto, T. [University of Tsukuba, Department of Neurosurgery, Tsukuba, Ibaraki (JP)] [and others

    2000-10-01

    It is difficult to measure boron concentration in blood during neutron irradiation in BNCT. We have investigated the predictability of boron concentration in blood from the data at 1st craniotomy after low dose BSH infusion. Two patients entered BNCT at JRR2 in 1995/1996, and 5 patients entered BNCT at JRR4 in 1992/2000. The patients include 2 male and 5 female and their age ranged from 20 to 66. In 5 patients 1 g of BSH was infused before 1st tumor removal operation and boron concentrations in blood were examined around this operation. All patients were infused 100 mg/kg of BSH at 12 hours prior to BNCT and boron concentrations were examined before and after BNCT using prompt gamma ray analysis or ICP-AES. Each results showed biphasic pharmacokinetic profile. Personal variations of the pharmacokinetics of BSH were small. Final and 1 g data were well correlated and final boron concentrations at BNCT were predictable from 1 g studies. (author)

  18. Effect of High-Dose Vitamin C Infusion in a Glucose-6-Phosphate Dehydrogenase-Deficient Patient

    Science.gov (United States)

    Gerber, Bryan; Kenyon, Katharine; Muthukanagaraj, Purushothaman

    2017-01-01

    Vitamin C supplementation is generally regarded as benign. There has been a resurgence of interest in the general medical community regarding the use of vitamin C most notably in the care of sepsis. Nonetheless, caution must be taken if supraphysiologic vitamin C supplementation is being administered as it should be considered a medication just like any other. We present a case of hemolysis in a glucose-6-phosphate dehydrogenase- (G6PD-) deficient patient receiving high-dose vitamin C infusions for his rheumatoid arthritis. PMID:29317868

  19. High dose benzodiazepine dependence: description of 29 patients treated with flumazenil infusion and stabilised with clonazepam.

    Science.gov (United States)

    Quaglio, Gianluca; Pattaro, Cristian; Gerra, Gilberto; Mathewson, Sophie; Verbanck, Paul; Des Jarlais, Don C; Lugoboni, Fabio

    2012-08-15

    The withdrawal syndrome from benzodiazepine (BZD) can be severe and in some cases may impede cessation of the use of the drug. We present here a case series of benzodiazepine detoxification by flumazenil infusion, stabilised with clonazepam. Patients were treated with flumazenil 1.35 mg/day for a median of 7 days. Self-reported physical withdrawal symptoms were recorded daily. In addition to flumazenil, antidepressants were given before treatment commenced and clonazepam was administered nightly with both being continued after discharge. Twenty-nine patients were treated. No patients dropped out from the treatment programme. Nine patients (31%) required a temporary reduction/cessation of the infusion. The linear trend in the reduction of the daily withdrawal scores in the overall study population was significant. The linear trends were also significant in the group of patients for whom a temporary reduction/suspension of the flumazenil was required. Six months after treatment, 15 patients (53%) were abstinent from clonazepam and other BZDs. For five (21%) the BZD dependence were reinstated. More than two-thirds of the subjects tolerated the procedure well and about half had a good long term response. Slow flumazenil infusion appears to merit consideration as a possible future treatment. Suggestions for future research are examined. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. Intravenous infusion of docosahexaenoic acid increases serum concentrations in a dose-dependent manner and increases seizure latency in the maximal PTZ model.

    Science.gov (United States)

    Trépanier, Marc-Olivier; Kwong, Kei-Man; Domenichiello, Anthony F; Chen, Chuck T; Bazinet, Richard P; Burnham, W M

    2015-09-01

    Docosahexaenoic acid (DHA) is an omega-3 polyunsaturated fatty acid (n-3 PUFA) that has been shown to raise seizure thresholds in the maximal pentylenetetrazole model following acute subcutaneous (s.c.) administration in rats. Following s.c. administration, however, the dose-response relationship for DHA has shown an inverted U-pattern. The purposes of the present experiment were as follows: (1) to determine the pattern of serum unesterified concentrations resulting from the intravenous (i.v.) infusions of various doses of DHA, (2) to determine the time course of these concentrations following the discontinuation of the infusions, and (3) to determine whether seizure protection in the maximal PTZ model would correlate with serum unesterified DHA levels. Animals received 5-minute i.v. infusions of saline or 25, 50, 100, or 200mg/kg of DHA via a cannula inserted into one of the tail veins. Blood was collected during and after the infusions by means of a second cannula inserted into the other tail vein (Experiment 1). A separate group of animals received saline or 12.5-, 25-, 50-, 100-, or 200 mg/kg DHA i.v. via a cannula inserted into one of the tail veins and were then seizure-tested in the maximal PTZ model either during infusion or after the discontinuation of the infusions. Slow infusions of DHA increased serum unesterified DHA concentrations in a dose-dependent manner, with the 200-mg/kg dose increasing the concentration approximately 260-fold compared with saline-infused animals. Following discontinuation of the infusions, serum concentrations rapidly dropped toward baseline, with half-lives of approximately 40 and 11s for the 25-mg/kg dose and 100-mg/kg dose, respectively. In the seizure-tested animals, DHA significantly increased latency to seizure onset in a dose-dependent manner. Following the discontinuation of infusion, seizure latency rapidly decreased toward baseline. Overall, our study suggests that i.v. infusion of unesterified DHA results in

  1. Infusion of low dose glyceryl trinitrate has no consistent effect on burrowing behavior, running wheel activity and light sensitivity in female rats

    DEFF Research Database (Denmark)

    Christensen, Sarah Louise T; Petersen, Steffen; Sørensen, Dorte Bratbo

    2016-01-01

    Introduction: Glyceryl trinitrate induces headache during infusion to man and migraine patients develop an additional migraine attack a few hours after the infusion. Recently, we have moved this model into rat with the intention of developing an animal model predictive of migraine therapy...... trinitrate on these behaviors in female rats was observed. Results: Burrowing behavior and running wheel activity were stable in the individual rat between experiments. The burrowing behavior was significantly affected by the stage of estrous cycle. The other assays were stable throughout the cycle. None...... testing and the effect of i.v. glyceryl trinitrate infusion to awake rats in three behavioral assays. Of the assays evaluated, only light sensitivity was capable of detecting changes after glyceryl trinitrate infusion but, this was not repeatable. Thus, the infusion of a low dose glyceryl trinitrate...

  2. Effects of Intracoronary Infusion of Escalating Doses of Cardiac Stem Cells in Rats With Acute Myocardial Infarction.

    Science.gov (United States)

    Tang, Xian-Liang; Rokosh, Gregg; Sanganalmath, Santosh K; Tokita, Yukichi; Keith, Matthew C L; Shirk, Gregg; Stowers, Heather; Hunt, Gregory N; Wu, Wenjian; Dawn, Buddhadeb; Bolli, Roberto

    2015-07-01

    Although c-kit(pos) cardiac stem cells (CSCs) preserve left ventricular (LV) function and structure after myocardial infarction, CSC doses have been chosen arbitrarily, and the dose-effect relationship is unknown. Rats underwent a 90-minute coronary occlusion followed by 35 days of reperfusion. Vehicle or CSCs at 5 escalating doses (0.3×10(6), 0.75×10(6), 1.5×10(6), 3.0×10(6), and 6.0×10(6) cells/heart) were given intracoronarily 4 h after reperfusion. The lowest dose (0.3×10(6)) had no effect on LV function and morphology, whereas 0.75, 1.5, and 3.0×10(6) significantly improved regional and global LV function (echocardiography and hemodynamic studies). These 3 doses had similar effects on echocardiographic parameters (infarct wall thickening fraction, LV end-systolic and end-diastolic volumes, LV ejection fraction) and hemodynamic variables (LV end-diastolic pressure, LV dP/dtmax, preload adjusted maximal power, end-systolic elastance, preload recruitable stroke work) and produced similar reductions in apoptosis, scar size, infarct wall thinning, and LV expansion index and similar increases in viable myocardium in the risk region (morphometry). Infusion of 6.0×10(6) CSCs markedly increased postprocedural mortality. Green fluorescent protein and 5-bromo-2'-deoxyuridine staining indicated that persistence of donor cells and formation of new myocytes were negligible with all doses. Surprisingly, in this rat model of acute myocardial infarction, the dose-response relationship for intracoronary CSCs is flat. A minimal dose between 0.3 and 0.75×10(6) is necessary for efficacy; above this threshold, a 4-fold increase in cell number does not produce greater improvement in LV function or structure. Further increases in cell dose are harmful. © 2015 American Heart Association, Inc.

  3. Concurrent chemoradiotherapy using protracted infusion of low-dose CDDP and 5-FU and radiotherapy for esophageal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Itoh, Yoshiyuki; Fuwa, Nobukazu; Matsumoto, Akira; Asano, Akiko; Sasaoka, Masahiro [Aichi Cancer Center, Nagoya (Japan). Hospital

    1999-07-01

    We evaluated the effects and safety of concurrent chemoradiotherapy for patients with esophageal cancer. Between March 1994 and April 1998, concurrent chemoradiotherapy using protracted infusion of low-dose cisplatin (CDDP: 3-6 mg/m{sup 2}/24 h), 5-fluorouracil (5-FU: 200 mg/m{sup 2}/24 h) and radiotherapy was given to 26 patients. The median age was 70 yr, with a range from 58 to 86 yr. With regard to TNM classification (1987), 6 patients were stage II, 5 stage III, and 15 stage IV. Radiotherapy was performed by external irradiation alone in 23 patients and external irradiation plus brachytherapy in three patients. One patient underwent surgery after a dose of 40 Gy owing to the possibility of idiopathic bleeding from the stomach. Locally, primary effects resulted in complete response in 11 patients (42.3%) and partial response in 15 (57.7%). Acute toxicity was primarily hematologic. Leukopenia and thrombocytopenia of grade 3 of 4 occurred in eight (30.7%) and six (23.0%) of 26 patients, respectively. In patients administered CDDP at more than 5 mg/m{sup 2}/day, hemotoxicity was severe because in five of the 10 patients administered 5 mg/m{sup 2} CDDP and one of the 2 patients administered 6 mg/m{sup 2} CDDP, thrombocytopenia of grade 3 or 4 occurred. Protracted infusion of low-dose CDDP and 5-FU with concomitant radiation therapy is effective, but from the point of acute toxicity, the optimal dose of CDDP and 5-FU needs further investigation. (author)

  4. Enantioselective disposition of omeprazole, pantoprazole, and lansoprazole in a same Brazilian subjects group.

    Science.gov (United States)

    Cassiano, Neila M; Oliveira, Regina V; Bernasconi, Gilberto C R; Cass, Quezia B

    2012-04-01

    This work reports the result of the enantioselective disposition of pantoprazole, omeprazole, and lansoprazole in a same group of Brazilian health subjects. Ten nongenotyped healthy subjects were used for this study. Each subject received a single oral dose of 80 mg of pantoprazole, 40 mg of omeprazole, and 30 mg of lansoprazole, and the plasma concentrations of the enantiomers were measured for 8 h postdose. For pantoprazole and omeprazole, among the 10 volunteers investigated, only one volunteer (Subject # 4) presented higher plasma concentrations of the (+)-enantiomer than those of (-)-enantiomer. Nevertheless, the area under the concentration-time curve of the (+)-lansoprazole was higher than those the (-)-lansoprazole for all subjects. The comparison of proton pump inhibitors' enantiomers disposition from a single group volunteer demonstrated that pantoprazole and omeprazole can be used to differentiate extensive from poor CYP2C19 metabolizer while lansoprazole cannot do it. Copyright © 2011 Wiley Periodicals, Inc.

  5. Pharmacokinetic drug interaction profile of omeprazole with adverse consequences and clinical risk management

    Directory of Open Access Journals (Sweden)

    Li W

    2013-05-01

    cancer resistance protein-mediated drug transport, and inhibition of oral absorption by gastric acid suppression. Sometimes, DDIs of omeprazole do not exhibit a PPI class effect. Other suitable PPIs or histamine 2 antagonists may be therapeutic alternatives that can be used to avoid adverse consequences. The degree of DDIs associated with omeprazole and clinical outcomes depend on factors such as genotype status of CYP2C19 and CYP1A2, ethnicity, dose and treatment course of precipitant omeprazole, pharmaceutical formulation of object drug (eg, mycophenolate mofetil versus enteric-coated mycophenolate sodium, other concomitant medication (eg, omeprazole-indinavir versus omeprazole–indinavir–ritonavir, and administration schedule (eg, intensified dosing of mycophenolate mofetil versus standard dosing.Conclusion: Despite the fact that omeprazole is one of the most widely prescribed drugs internationally, clinical professionals should enhance clinical risk management on adverse DDIs associated with omeprazole and ensure safe combination use of omeprazole by rationally prescribing alternatives, checking the appropriateness of physician orders before dispensing, and performing therapeutic drug monitoring.Keywords: administration schedule, drug interactions, drug toxicity, herb–drug interactions, omeprazole, pharmacokinetics, polypharmacy, prescription auditing, risk management, treatment failure

  6. A study to determine minimum effective dose of oxytocin infusion during caesarean delivery in parturients at high risk of uterine atony

    Directory of Open Access Journals (Sweden)

    Shashikiran

    2017-01-01

    Full Text Available Background: Oxytocin, a commonly used drug to prevent uterine atony after caesarean section, should be administered as dilute rapid infusion rather than as a bolus. This study was conducted to calculate ED90 of oxytocin infusion during caesarean delivery in parturients at high risk of postpartum haemorrhage (PPH. Materials and Methods: One hundred and twenty parturients having one or more risk factors for PPH received a blinded infusion of oxytocin following emergency caesarean delivery. The initial dose of oxytocin infusion was started as 0.4 IU min−1. The dose of oxytocin infusion for the next parturient was based on the response of preceding patient in increments or decrements of 0.1 IU min−1 as per a biased-coin design up-down sequential method (UDM. Measurements of non-invasive blood pressure and heart rate were taken at 2 min intervals from the time of oxytocin infusion. Intraoperative blood loss was noted. Side effects such as tachycardia, hypotension, nausea, vomiting, chest pain, headache and flushing were also recorded. Results: The ED90 of oxytocin infusion was found to be 0.405 IU min−1 (95% confidence interval 0.3864–0.4125 as calculated by Firth's penalised likelihood estimation using a biased-coin design UDM. Hypotension was observed for brief period of time in 25.6% of parturients and brief period of tachycardia was observed in 9.4% of parturients. No headache, flushing, chest pain and vomiting were observed in any parturients in our study. The estimated blood loss was within the normal limits. Conclusion: Our study showed that ED90 of oxytocin infusion required to achieve adequate uterine tone (UT after an emergency caesarean delivery in parturients at high risk of uterine atony was 0.405 IU min−1. The higher doses of oxytocin did not result in further improvement of UT. Therefore, early use of alternative uterotonic therapy is preferable to achieve adequate UT.

  7. Non-ST Elevation Myocardial Infraction after High Dose Intravenous Immunoglobulin Infusion

    Directory of Open Access Journals (Sweden)

    Meir Mizrahi

    2009-01-01

    Full Text Available Intravenous immunoglobulins (IVIgs are used for several indications, including autoimmune conditions. IVIg treatment is associated with several possible adverse reactions including induction of a hypercoagulable state. We report a 76-year-old woman treated with IVIg for myasthenia gravis, which developed chest pain and weakness following IVIg infusion. The symptoms were associated with ST segment depression in V4–6 and elevated troponin levels. The patient was diagnosed with non-ST elevation myocardial infarction (NSTEMI. The patient had no significant risk factor besides age and a cardiac perfusion scan was interpreted as normal (the patient refused to undergo cardiac catheterization. This case is compatible with IVIg-induced hypercoagulability resulting in NSTEMI. Cardiac evaluation should therefore be considered prior to initiation of IVIg treatment especially in patients with multiple cardiovascular risks.

  8. Dose-effects of aorta-infused clenbuterol on spinal cord ischemia-reperfusion injury in rabbits.

    Directory of Open Access Journals (Sweden)

    Binbin Chen

    Full Text Available BACKGROUND: The β2 adrenergic receptor (β2AR plays an important role in ischemia-reperfusion (I/R injury in various organs. Recently, a selective β2AR agonist clenbuterol was suggested to protect against cerebral I/R injury. This study was designed to investigate changes of β2ARs after spinal cord I/R injury and dose-effects of aorta-infused clenbuterol on spinal cord I/R injury in rabbits. METHODS: Spinal cord ischemia was induced in New Zealand white rabbits by infrarenal abdominal aortic occlusion with a balloon catheter for 30 minutes except the sham group. During occlusion, nothing (I/R group, normal saline (NS group or clenbuterol at different doses of 0.005, 0.01, 0.05, 0.1, 0.5, or 1 mg/kg (C0.005, C0.01, C0.05, C0.1, C0.5, and C1 groups was infused into the occluded aortic segments. The hemodynamic data, blood glucose and serum electrolytes were measured during experimental period. Neurological function was assessed according to the modified Tarlov scales until 48 hours after reperfusion. After that, the lumbar spinal cord was harvested for β2AR immunohistochemistry and histopathologic evaluation in the anterior horns. RESULTS: The β2AR expression in the anterior horns of the spinal cord was significantly higher in the I/R group than in the sham group. Tarlov scores and the number of viable α-motor neurons were higher in C0.01-C0.5 groups than in the NS group, C0.005 and C1 groups and were highest in the C0.1 group. Hypotension and hyperglycemia were found in the C1 group. CONCLUSION: β2ARs in the anterior horn were upregulated after spinal cord I/R injury. Aortic-infused clenbuterol (0.01-0.5 mg/kg can attenuate spinal cord I/R injury dose-dependently during the ischemic period. The Optimal dosage was 0.1 mg/kg. Activation of β2AR could be a new therapeutic strategy for the treatment of spinal cord I/R injury.

  9. Dose-effects of aorta-infused clenbuterol on spinal cord ischemia-reperfusion injury in rabbits.

    Science.gov (United States)

    Chen, Binbin; Zhang, Yi; Chen, Lianhua; Huang, Shiwei; Li, Shitong; Yao, Junyan

    2013-01-01

    The β2 adrenergic receptor (β2AR) plays an important role in ischemia-reperfusion (I/R) injury in various organs. Recently, a selective β2AR agonist clenbuterol was suggested to protect against cerebral I/R injury. This study was designed to investigate changes of β2ARs after spinal cord I/R injury and dose-effects of aorta-infused clenbuterol on spinal cord I/R injury in rabbits. Spinal cord ischemia was induced in New Zealand white rabbits by infrarenal abdominal aortic occlusion with a balloon catheter for 30 minutes except the sham group. During occlusion, nothing (I/R group), normal saline (NS group) or clenbuterol at different doses of 0.005, 0.01, 0.05, 0.1, 0.5, or 1 mg/kg (C0.005, C0.01, C0.05, C0.1, C0.5, and C1 groups) was infused into the occluded aortic segments. The hemodynamic data, blood glucose and serum electrolytes were measured during experimental period. Neurological function was assessed according to the modified Tarlov scales until 48 hours after reperfusion. After that, the lumbar spinal cord was harvested for β2AR immunohistochemistry and histopathologic evaluation in the anterior horns. The β2AR expression in the anterior horns of the spinal cord was significantly higher in the I/R group than in the sham group. Tarlov scores and the number of viable α-motor neurons were higher in C0.01-C0.5 groups than in the NS group, C0.005 and C1 groups and were highest in the C0.1 group. Hypotension and hyperglycemia were found in the C1 group. β2ARs in the anterior horn were upregulated after spinal cord I/R injury. Aortic-infused clenbuterol (0.01-0.5 mg/kg) can attenuate spinal cord I/R injury dose-dependently during the ischemic period. The Optimal dosage was 0.1 mg/kg. Activation of β2AR could be a new therapeutic strategy for the treatment of spinal cord I/R injury.

  10. Omeprazole and lansoprazole enantiomers induce CYP3A4 in human hepatocytes and cell lines via glucocorticoid receptor and pregnane X receptor axis.

    Science.gov (United States)

    Novotna, Aneta; Dvorak, Zdenek

    2014-01-01

    Benzimidazole drugs lansoprazole and omeprazole are used for treatment of various gastrointestinal pathologies. Both compounds cause drug-drug interactions because they activate aryl hydrocarbon receptor and induce CYP1A genes. In the current paper, we examined the effects of lansoprazole and omeprazole enantiomers on the expression of key drug-metabolizing enzyme CYP3A4 in human hepatocytes and human cancer cell lines. Lansoprazole enantiomers, but not omeprazole, were equipotent inducers of CYP3A4 mRNA in HepG2 cells. All forms (S-, R-, rac-) of lansoprazole and omeprazole induced CYP3A4 mRNA and protein in human hepatocytes. The quantitative profiles of CYP3A4 induction by individual forms of lansoprazole and omeprazole exerted enantiospecific patterns. Lansoprazole dose-dependently activated pregnane X receptor PXR in gene reporter assays, and slightly modulated rifampicin-inducible PXR activity, with similar potency for each enantiomer. Omeprazole dose-dependently activated PXR and inhibited rifampicin-inducible PXR activity. The effects of S-omeprazole were much stronger as compared to those of R-omeprazole. All forms of lansoprazole, but not omeprazole, slightly activated glucocorticoid receptor and augmented dexamethasone-induced GR transcriptional activity. Omeprazole and lansoprazole influenced basal and ligand inducible expression of tyrosine aminotransferase, a GR-target gene, in HepG2 cells and human hepatocytes. Overall, we demonstrate here that omeprazole and lansoprazole enantiomers induce CYP3A4 in HepG2 cells and human hepatocytes. The induction comprises differential interactions of omeprazole and lansoprazole with transcriptional regulators PXR and GR, and some of the effects were enantiospecific. The data presented here might be of toxicological and clinical importance, since the effects occurred in therapeutically relevant concentrations.

  11. Omeprazole and lansoprazole enantiomers induce CYP3A4 in human hepatocytes and cell lines via glucocorticoid receptor and pregnane X receptor axis.

    Directory of Open Access Journals (Sweden)

    Aneta Novotna

    Full Text Available Benzimidazole drugs lansoprazole and omeprazole are used for treatment of various gastrointestinal pathologies. Both compounds cause drug-drug interactions because they activate aryl hydrocarbon receptor and induce CYP1A genes. In the current paper, we examined the effects of lansoprazole and omeprazole enantiomers on the expression of key drug-metabolizing enzyme CYP3A4 in human hepatocytes and human cancer cell lines. Lansoprazole enantiomers, but not omeprazole, were equipotent inducers of CYP3A4 mRNA in HepG2 cells. All forms (S-, R-, rac- of lansoprazole and omeprazole induced CYP3A4 mRNA and protein in human hepatocytes. The quantitative profiles of CYP3A4 induction by individual forms of lansoprazole and omeprazole exerted enantiospecific patterns. Lansoprazole dose-dependently activated pregnane X receptor PXR in gene reporter assays, and slightly modulated rifampicin-inducible PXR activity, with similar potency for each enantiomer. Omeprazole dose-dependently activated PXR and inhibited rifampicin-inducible PXR activity. The effects of S-omeprazole were much stronger as compared to those of R-omeprazole. All forms of lansoprazole, but not omeprazole, slightly activated glucocorticoid receptor and augmented dexamethasone-induced GR transcriptional activity. Omeprazole and lansoprazole influenced basal and ligand inducible expression of tyrosine aminotransferase, a GR-target gene, in HepG2 cells and human hepatocytes. Overall, we demonstrate here that omeprazole and lansoprazole enantiomers induce CYP3A4 in HepG2 cells and human hepatocytes. The induction comprises differential interactions of omeprazole and lansoprazole with transcriptional regulators PXR and GR, and some of the effects were enantiospecific. The data presented here might be of toxicological and clinical importance, since the effects occurred in therapeutically relevant concentrations.

  12. Effect of fentanyl on the induction dose and minimum infusion rate of propofol preventing movement in dogs.

    Science.gov (United States)

    Davis, Carrie A; Seddighi, Reza; Cox, Sherry K; Sun, Xiaocun; Egger, Christine M; Doherty, Thomas J

    2017-07-01

    To determine the effect of fentanyl on the induction dose of propofol and minimum infusion rate required to prevent movement in response to noxious stimulation (MIR NM ) in dogs. Crossover experimental design. Six healthy, adult intact male Beagle dogs, mean±standard deviation 12.6±0.4 kg. Dogs were administered 0.9% saline (treatment P), fentanyl (5 μg kg -1 ) (treatment PLDF) or fentanyl (10 μg kg -1 ) (treatment PHDF) intravenously over 5 minutes. Five minutes later, anesthesia was induced with propofol (2 mg kg -1 , followed by 1 mg kg -1 every 15 seconds to achieve intubation) and maintained for 90 minutes by constant rate infusions (CRIs) of propofol alone or with fentanyl: P, propofol (0.5 mg kg -1  minute -1 ); PLDF, propofol (0.35 mg kg -1  minute -1 ) and fentanyl (0.1 μg kg -1  minute -1 ); PHDF, propofol (0.3 mg kg -1  minute -1 ) and fentanyl (0.2 μg kg -1  minute -1 ). Propofol CRI was increased or decreased based on the response to stimulation (50 V, 50 Hz, 10 mA), with 20 minutes between adjustments. Data were analyzed using a mixed-model anova and presented as mean±standard error. ropofol induction doses were 6.16±0.31, 3.67±0.21 and 3.33±0.42 mg kg -1 for P, PLDF and PHDF, respectively. Doses for PLDF and PHDF were significantly decreased from P (pFentanyl, at the doses studied, caused statistically significant and clinically important decreases in the propofol induction dose and MIR NM . Copyright © 2017 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.

  13. Obstructive Prosthetic Mitral Valve Thrombosis Successfully Thrombolysed with Low-Dose Ultra-Slow Infusion of Tissue Plasminogen Activator

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    Macit Kalçık

    2015-01-01

    Full Text Available Prosthetic valve thrombosis (PVT is one of the major causes of posthetic heart valve failure. Treatment modalities for this rare but life threatening complication include anticoagulation with heparin, thrombolytic therapy (TT and re-do valve surgery. Guidelines lack definitive class I recommendations due to lack of randomised controlled trials, and usually leave the choice of treatment to the clinician’s experience. Surgery is suggested as a first line strategy in most situations of left sided PVT; however, TT has been recently used with successful outcomes1-3. This report describes a patient with giant thrombus located on the prosthetic mitral valve, which was succesfully treated with ultraslow infusion (25 hours of low dose (25 mg tissue plasminogen activator (tPA under the guidance of two-dimensional (2D and real-time three-dimensional (RT -3D transesophageal echocardiography (TEE and fluoroscopy.

  14. Role of omeprazole dosage and cytochrome P450 2C19 genotype in patients receiving omeprazole-amoxicillin dual therapy for Helicobacter pylori eradication.

    Science.gov (United States)

    Yang, Jyh-Chin; Wang, Hong-Long; Chern, Herng-Der; Shun, Chia-Tung; Lin, Bor-Ru; Lin, Chun-Jung; Wang, Teh-Hong

    2011-03-01

    To determine the factors that may influence Helicobacter pylori eradication in patients receiving omeprazole-amoxicillin dual therapy. Prospective, randomized study. University-affiliated hospital in Taiwan. A total of 128 adults (age range 20-75 yrs) with H. pylori-positive duodenal ulcer were enrolled; 121 completed the final evaluation. Patients were randomly assigned to one of four omeprazole-amoxicillin treatment groups, with each treatment administered for 2 weeks: O2A2 group (33 patients)--omeprazole 20 mg twice/day plus amoxicillin 500 mg 4 times/day; O2A1 group (32 patients)--omeprazole 20 mg twice/day plus amoxicillin 250 mg 4 times/day; O1A2 group (32 patients)--omeprazole 20 mg once/day plus amoxicillin 500 mg 4 times/day; and O1A1 group (31 patients)--omeprazole 20 mg once/day plus amoxicillin 250 mg 4 times/day. Data were collected on H. pylori status, histologic parameters, antibiotic resistance, intragastric pH, cytochrome P450 (CYP) 2C19 genotype, and adverse reactions. The intent-to-treat cure rates (95% confidence interval [CI]) in groups O2A2, O2A1, O1A2, and O1A1 were 76% (95% CI 59-87%), 72% (95% CI 54-84%), 50% (95% CI 34-66%) and 52% (95% CI 35-68%), respectively. Eradication of H. pylori infection was statistically significantly dependent on omeprazole dosage, CYP2C19 genotype, age, gastritis status, and H. pylori density. All CYP2C19 poor metabolizers were cured, whereas the H. pylori cure rate in CYP2C19 extensive metabolizers varied from 44-76% in the different treatment groups. Eradication of H. pylori was favored in the omeprazole higher dose groups versus the lower dose groups (79% vs 53%, p=0.004). No secondary antibiotic resistance was found. Thirty-seven (95%) of 39 patients who failed with the initial treatment were cured by subsequent antibiotic susceptibility-driven proton pump inhibitor-based triple therapy. Provided a maintenance dose of amoxicillin is given every 6 hours, eradication of H. pylori infection was significantly

  15. Gastric polyps and nodules in children receiving long-term omeprazole therapy.

    Science.gov (United States)

    Pashankar, Dinesh S; Israel, David M

    2002-11-01

    Multiple gastric polyps have been reported to occur in adults receiving omeprazole therapy. There are little published data in children. We report our experience in monitoring the gross and histologic appearance of the stomach in children receiving long-term omeprazole therapy. This was a retrospective review of the charts of children who received omeprazole for more than 6 months for reflux esophagitis between 1989 and 1998. All patients had repeated endoscopic examinations until healing of the esophagitis was confirmed and then annually thereafter. At endoscopy, gastric mucosal swellings were classified as polyps or nodules based on histology. Thirty-one children had long-term endoscopic follow-up while receiving omeprazole. Seven of 31 children had gastric polyps and/or nodules, noted between 10 and 48 months (mean = 28 months) of omeprazole therapy. Four had nodules only, one had a sessile hyperplastic polyp, and two had both a polyp (one hyperplastic and one fundic gland polyp) and nodules. All lesions were found in the gastric body. Nodules in four of the six children disappeared spontaneously while the children continued to receive omeprazole. The polyps persisted. There were no dysplastic changes in the gastric mucosa or polyps in any of the patients. There were no significant differences between the 7 children with and the 24 without polyps/nodules with respect to age, gastrin concentrations, or dose and duration of omeprazole therapy. Gastric polyps and nodules may be found in children receiving long-term omeprazole therapy. The gastric changes in our patients were benign during the mean observation period of 31 months.

  16. 21 CFR 520.1615 - Omeprazole.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Omeprazole. 520.1615 Section 520.1615 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1615 Omeprazole. (a) Specifications. Each gram of paste contains 0.37 gram...

  17. Omeprazole-induced hypertrichosis in two children.

    Science.gov (United States)

    Elosua-González, Marta; Campos-Domínguez, Minia; Bancalari, Daniel; Noguera-Morel, Lucero; Hernández-Martín, Angela; Huerta-Aragonés, Jorge; Torrelo, Antonio

    2018-03-26

    Omeprazole significantly increases duodenal prostaglandin E 2 synthesis. Prostaglandins are involved in hair growth regulation: prostaglandin E 2 and prostaglandin F 2 alpha stimulate hair growth, and prostaglandin D 2 has an inhibitory effect. The use of omeprazole can cause acquired generalized hypertrichosis by increasing prostaglandin E 2 levels. © 2018 Wiley Periodicals, Inc.

  18. Early effects of oral administration of esomeprazole and omeprazole on the intragastric pH.

    Science.gov (United States)

    Iida, Hiroshi; Inamori, Masahiko; Okuno, Kotone; Sekino, Yusuke; Sakai, Eiji; Okubo, Hidenori; Higurashi, Takuma; Endo, Hiroki; Hosono, Kunihiro; Yoneda, Masato; Koide, Tomoko; Takahashi, Hirokazu; Goto, Ayumu; Kubota, Kensuke; Saito, Satoru; Maeda, Shin; Nakajima, Atsushi; Gotoh, Eiji

    2015-01-01

    The aim of our study was to investigate the inhibitory effects on gastric acid secretion of a single oral dose of a proton pump inhibitor, esomeprazole 20 mg and omeprazole 20 mg. A total of 14 Helicobacter pylori-negative male subjects participated in this study. Intragastric pH was monitored continuously for 6 hours after a single oral dose of omeprazole 20 mg and a single oral dose of esomeprazole 20 mg. Each administration was separated by a 7-day washout period. During the 6-hour study period, the average pH after administration of esomeprazole was higher than that after the administration of omeprazole. Also during the 6-hour study period, each of pH > 2, 3, 3.5, 4, and 5 was maintained for a longer duration after administration of esomeprazole 20 mg than after administration of omeprazole 20 mg (median: 75.4% vs. 53.8%, p = 0.0138; 52.1% vs. 33.4%, p = 0.0188; 45.8% vs. 28.2%, p = 0.0262; 42.5% vs. 20.7%, p = 0.0414; 35.8% vs. 11.6%, p = 0.0262; respectively). In Helicobacter pylori-negative healthy male subjects, single oral administration of esomeprazole 20 mg increased the intragastric pH more rapidly than single oral administration of omeprazole 20 mg.

  19. Identification of two main urinary metabolites of (/sup 14/C)omeprazole in humans

    Energy Technology Data Exchange (ETDEWEB)

    Renberg, L.; Simonsson, R.; Hoffmann, K.J.

    1989-01-01

    The excretion and metabolism of (/sup 14/C)omeprazole given orally as a suspension was studied in 10 healthy male subjects. An average of 79% of the dose was recovered in the urine in 96 hr, with most of the radioactivity (76% of dose) being eliminated in the first 24 hr. Pooled urine (0-2 hr) from five subjects, containing about 47% of the dose, was analyzed by reverse phase gradient elution LC with radioisotope detection. Omeprazole was completely metabolized to at least six metabolites. The two major metabolites were extensively purified by LC and their structures were determined by MS with derivatization and use of stable isotopes, 1H NMR, and comparison with synthetic references. They were formed by hydroxylation of a methyl group in the pyridine ring, followed by further oxidation of the alcohol to the corresponding carboxylic acid. Both metabolites retained the sulfoxide group of omeprazole, rendering them as unstable as the parent compound at pH less than 7. They accounted for approximately 28% (hydroxyomeprazole) and 23% (omeprazole acid) of the amount excreted in the 0-2-hr collection interval. Based on in vitro studies with the synthetic metabolites in isolated gastric glands, it is unlikely that M1 and M2 will contribute to the pharmacological effect of omeprazole in humans.

  20. Phase I dose-escalating study of docetaxel in combination with 5-day continuous infusion of 5-fluorouracil in patients with advanced gastric cancer

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    Lee Jae

    2005-07-01

    Full Text Available Abstract Background Published data suggests that docetaxel combined with 5-fluorouracil (5-FU may have synergistic activity in treating advanced gastric cancer. We performed a phase I study of docetaxel and 5-FU to determine the maximum tolerated dose (MTD, the recommended dose for phase II studies, and the safety of this combination. Methods Eligible patients had recurrent and/or metastatic advanced gastric cancer with normal cardiac, renal and hepatic function. Traditional phase I methodology was employed in assessing dose-limiting toxicity (DLT and MTD. On day 1 every 3 weeks, docetaxel 75 mg/m2 (fixed dose was infused over 1-h, followed immediately by 5-FU as a 5-day continuous infusion. Results Dose escalation schema was as follows: dose level (DL 1 (5-FU 250 mg/m2/day, 2 (500, 3 (750, and 4 (1000. Three patients were enrolled on DL1, without DLT. On DL2, 1 DLT (grade 3 stomatitis was developed in first 3 patients, and this cohort was expanded to 6 patients. Three patients had been enrolled on DL3. Because two out of 3 patients had DLTs, the MTD was reached at DL3. Conclusion The recommended phase II dose of this combination is 75 mg/m2 docetaxel on day 1 immediately followed by a 5-day continuous infusion of 5-FU 500 mg/m2/day.

  1. Dose and time response of ruminally infused algae on rumen fermentation characteristics, biohydrogenation and Butyrivibrio group bacteria in goats.

    Science.gov (United States)

    Zhu, Honglong; Fievez, Veerle; Mao, Shengyong; He, Wenbo; Zhu, Weiyun

    2016-01-01

    Micro-algae could inhibit the complete rumen BH of dietary 18-carbon unsaturated fatty acid (UFAs). This study aimed to examine dose and time responses of algae supplementation on rumen fermentation, biohydrogenation and Butyrivibrio group bacteria in goats. Six goats were used in a repeated 3 × 3 Latin square design, and offered a fixed diet. Algae were infused through rumen cannule with 0 (Control), 6.1 (L-Alg), or 18.3 g (H-Alg) per day. Rumen contents were sampled on d 0, 3, 7, 14 and 20. H-Alg reduced total volatile fatty acid concentration and acetate molar proportion (P Algae induced a dose-dependent decrease in 18:0 and increased trans-18:1 in the ruminal content (P Algae had no effect on the abundances of Butyrivibrio spp. and Butyrivibrio proteoclasticus (P > 0.10), while H-Alg reduced the total bacteria abundance (P algae were related to the supplementation level, but there was no evidence of shift in ruminal biohydrogenation pathways towards t10-18:1. L-Alg mainly induced a transient effect on rumen biohydrogenation of 18-carbon UFAs, while H-Alg showed an acute inhibition and these effects were not associated with the known hydrogenating bacteria.

  2. Comparative Study of Continuous Pralidoxime Infusion versus Intermittent Dosing: Application of High-Performance Liquid Chromatography Method on Serum of Organophosphate Poisoned Patients

    Directory of Open Access Journals (Sweden)

    Girish Thunga

    2013-09-01

    How to cite this article: Thunga G, Pandey S, Nair S, Mylapuri R, Vidyasagar S, Kunhikatta V, et al. Comparative Study of Continuous Pralidoxime Infusion versus Intermittent Dosing: Application of High-Performance Liquid Chromatography Method on Serum of Organophosphate Poisoned Patients. Asia Pac J Med Toxicol 2013;2:105-10.

  3. Intravenous nicotine self-administration and cue-induced reinstatement in mice: Effects of nicotine dose, rate of drug infusion and prior instrumental training

    Science.gov (United States)

    Fowler, Christie D.; Kenny, Paul J.

    2011-01-01

    Intravenous nicotine self-administration is the most direct measure of nicotine reinforcement in laboratory animals, but this procedure has proven difficult to establish in mice. We found that stable responding for nicotine in C57BL6/J mice was facilitated by prior instrumental training for food reward, initial exposure of mice to a lower unit dose of nicotine (0.03 mg/kg/infusion) before access to higher doses, a slower rate of drug delivery (3-sec versus 1-sec infusion), consistency in schedule of daily testing, and low extraneous noise during testing. Under these conditions, we found that mice lever-pressing for nicotine (0.03–0.4 mg/kg/infusion; 60-min test sessions) under a fixed-ratio 5 time-out 20-sec (FR5TO20) reinforcement schedule consumed the drug according to an inverted ‘U’-shaped dose-response curve. Mice switched their responding onto a previously non-reinforced lever to continue earning nicotine infusions when the active/inactive lever assignment was reversed. The nicotinic acetylcholine receptor (nAChR) antagonist mecamylamine decreased responding for nicotine, but not food rewards, verifying that nAChRs regulate nicotine self-administration in mice. The cue-light paired with nicotine delivery did not support responding when delivered independently of nicotine infusions, further verifying that mice responded selectivity for the drug. Nicotine-seeking responses extinguished when nicotine infusions and the cue-light were withheld, and exposure to the cue-light reinstated responding. Finally, mice without prior instrumental food training acquired stable responding for nicotine under the FR5TO20 schedule, but required a greater number of sessions. These data demonstrate that nicotine is an effective reinforcer in mice and establish conditions under which the drug is reliably self-administered by mice. PMID:21640128

  4. A comparative pharmacodynamic study of IY-81149 versus omeprazole in patients with gastroesophageal reflux disease.

    Science.gov (United States)

    Periclou, A P; Goldwater, R; Lee, S M; Park, D W; Kim, D Y; Cho, K D; Boileau, F; Jung, W T

    2000-09-01

    To evaluate and compare the pharmacodynamic effects of IY-81149 and omeprazole on gastric pH in patients with gastroesophageal reflux disease. Sixty male and female volunteers with gastroesophageal reflux disease were enrolled in a double-blind, two-way, crossover, dose-ranging study. Subjects were randomized into three groups, with each group comparing the effect of one of three doses of IY-81149 (5, 10, or 20 mg) with 20 mg omeprazole. IY-81149 and omeprazole were administered once daily for 5 days. Continuous 24-hour pH measurements were performed before the first dose (baseline) and after the fifth dose in both periods. Gastric acid suppression was evaluated on the basis of the following parameters: AUC(0-24), median pH in a 24-hour interval (pHmedian), and the percent time in a 24-hour interval in which the gastric pH was greater than 4 (tpH > 4). The truncated AUC parameters AUC(0-8), AUC(8-16), and AUC(16-24) were also calculated. The effects of IY-81149 and omeprazole on gastric pH were compared by use of analyses of covariance. The dose-response relationship for IY-81149 was also evaluated. There were no statistically significant differences between 5 mg IY-81149 and 20 mg omeprazole in terms of AUC(0-24), pHmedian, tpH, 4, AUC(0-8), and AUC(8-16). IY-81149, at 10 mg, produced a significantly greater gastric acid suppression than omeprazole on the basis of the values of AUC(0-24), pHmedian, tpH > 4, AUC(8-16), and AUC(16-24). Administration of 20 mg IY-81149 produced a significantly greater gastric acid suppression on the basis of all parameters. All doses of IY-81149 were more effective than omeprazole during 16 to 24 hours after the dose was administered. Administration of 10 and 20 mg IY-81149 produced a statistically significantly greater and prolonged suppression of gastric pH than 20 mg omeprazole.

  5. Effects of Omeprazole on Iron Absorption: Preliminary Study

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    Mahmut Yaşar Çeliker

    2013-09-01

    Full Text Available Objective: Increasing numbers of pediatric and adult patients are being treated with proton pump inhibitors (PPIs. PPIs are known to inhibit gastric acid secretion. Nonheme iron requires gastric acid for conversion to the ferrous form for absorption. Ninety percent of dietary and 100% of oral iron therapy is in the nonheme form. To the best of our knowledge, the effect of PPIs on iron absorption has not been studied in humans. Our study assessed the relationship between omeprazole therapy and iron absorption in healthy subjects. Materials and Methods: We recruited 9 healthy volunteers between June 2010 and March 2011. Subjects with chronic illness, anemia, or use of PPI therapy were excluded. Serum iron concentrations were measured 1, 2, and 3 h after the ingestion of iron (control group. The measurements were repeated on a subsequent visit after 4 daily oral administrations of omeprazole at a dose of 40 mg (treatment group. Results: One female and 8 male volunteers were enrolled in the study with a mean age of 33 years. There was no statistical difference detected between baseline, 1-h, 2-h, and 3-h iron levels between control and treatment groups. Conclusion: Administration of omeprazole for a short duration does not affect absorption of orally administered iron in healthy individuals.

  6. Effects of omeprazole in improving concurrent chemoradiotherapy efficacy in rectal cancer.

    Science.gov (United States)

    Zhang, Jin-Liang; Liu, Min; Yang, Qing; Lin, Shi-Yong; Shan, Hong-Bo; Wang, Hui-Yun; Xu, Guo-Liang

    2017-04-14

    To explore the effects of omeprazole on chemoradiotherapy efficacy and tumor recurrence in rectal cancer. The medical data of 125 rectal cancer patients who received the same neoadjuvant chemoradiotherapy (CRT) followed by surgery were retrospectively collected. Patients who received omeprazole (OME) orally at a dose of 20 mg at least once daily for six days and/or intravenously at 40 mg a day were recognized as eligible OME users (EOU). Otherwise, patients were regarded as non-eligible OME users (non-EOU). Moreover, a preferred OME dose cut-off of 200 mg on tumor recurrence was obtained by receiver operating characteristic (ROC) curves. Patients were divided into two groups: the effective OME group (EOG, OME ≥ 200 mg) and the non-effective OME group (non-EOG, OME cancer treatment for relieving common side effects of chemotherapy, omeprazole has a synergetic effect in improving CRT efficacy and decreasing rectal cancer recurrence.

  7. Lack of drug interaction between omeprazole, lansoprazole, pantoprazole and theophylline

    Science.gov (United States)

    Dilger, Karin; Zheng, Zhichang; Klotz, Ulrich

    1999-01-01

    Aims Theophylline is a model substrate of cytochrome P4501A2. The ability of the proton pump inhibitors (PPI) omeprazole, lansoprazole and pantoprazole to induce cytochrome P4501A2 has not yet been unequivocally resolved. The aim of this comprehensive study was to compare directly the effect of the three PPI on the absorption and disposition of theophylline. Methods Twenty healthy, nonsmoking, male and female volunteers (extensive metabolisers of cytochrome P4502C19 and Helicobacter pylori negative) participated in a randomized, double-blind, four-period, placebo-controlled crossover study. In each of the four periods they received either omeprazole (40 mg), lansoprazole (60 mg), pantoprazole (80 mg) or placebo once daily for 10 days. Sustained release theophylline (350 mg twice daily) was coadministered from day 8–10. Pharmacokinetics of theophylline as well as of all three PPI were determined at steady-state (day 10). Results In all periods, point estimates and 90% confidence intervals of the area under the concentration-time curves (AUC), maximum steady-state concentrations and peak-trough fluctuations of theophylline were not altered by PPI pretreatment and met the required limits for bioequivalence. Point estimates (90% confidence intervals) of the AUC ratios of theophylline plus PPI to theophylline alone were 0.92 (0.87–0.97), 0.90 (0.85–0.95) and 1.00 (0.95–1.06) for omeprazole, lansoprazole and pantoprazole, respectively. Conclusions Concomitant intake of omeprazole, lansoprazole or pantoprazole at high therapeutic doses does not affect the absorption and disposition of theophylline. PMID:10510158

  8. Occupational contact allergy to omeprazole and ranitidine

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    Inmaculada Herrera-Mozo

    2017-06-01

    Full Text Available Omeprazole is a proton pump inhibition and ranitidine is an H2 histamine receptor antagonist widely used in the treatment of gastroesophageal reflex disease, peptic ulcer disease, Zollinger-Ellison syndrome and as a protector of the gastric mucosae. We report a case of occupational contact allergy to omeprazole and ranitidine. A 48-year-old man, with no pre-existing history of atopy or lifestyle factors. He neither had any medical history of consumption of drugs such as ranitidine and omeprazole. He worked for 19 months in the pharmaceutical company that manufactured ranitidine base. He presented rash in the face and eczema on the dorsum of the hands with itching. The study by prick tests with ranitidine gave negative response. Patch testing with ranitidine base and ranitidine hydrochloride gave positive response. A month later, when the patient was asymptomatic he returned to the pharmaceutical company, being switched from this previous job to the reactor manufacturing omeprazole. A few days after that, he presented erythematous eruptions involving face and neck with itching. Prick tests, path tests and in vitro laboratories studies with omeprazole gave positives. In this case the patient presented hypersensitivity type I at omeprazole and hypersensitivity type IV at omeprazole and ranitidine. Our aportation indicates the importance of careful analysis of the occupational exposure histories of patients with the suspected type I or type IV hypersensitivity to allergens, to determine whether work exposure is the cause. Med Pr 2017;68(3:433–435

  9. Alleviating stress response to tracheal extubation in neurosurgical patients: A comparative study of two infusion doses of dexmedetomidine

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    Ankur Luthra

    2017-01-01

    Full Text Available Background: Tracheal extubation is almost always associated with increase in sympathoadrenal activity may result in hypertension, tachycardia, and arrhythmias. Attempts have been made to oppose the pressor response by the use of various drugs. Dexmedetomidine decreases norepinephrine which reduces the blood pressure and the heart rate (HR. We hypothesize that the infusion of dexmedetomidine may produce more stable hemodynamics during extubation as compared to boluses. Materials and Methods: Ninety adult patients aged 18–65 years, the American Society of Anesthesiologists Grade I–II undergoing intracranial surgeries for various neurologic problem at All India Institute of Medical Sciences were enrolled in this randomized controlled trial. Primary Objectives: (1 To observe the hemodynamic changes (HR and mean arterial pressure [MAP] and airway responses during tracheal extubation following two infusion doses of dexmedetomidine. Secondary Objectives: (1 Time to emergence and time to tracheal extubation, (2 Early postoperative complications such as laryngospasm and bronchospasm, and (3 adverse effects of the study drug. Patients were assigned into three groups – (1 Group D0.2 – 0.2 μg/kg/h diluted to 50 ml, (2 Group D0.4 – 0.4 μg/kg/h diluted to 50 ml and Group P (Placebo – 0.9% NS 50 ml. The hemodynamics including the HR and MAP were recorded just before the loading dose of the study drug and then were recorded every 5 min till the infusion was stopped at tracheal extubation and every 1 min till 10 min postextubation. In addition, the airway, respiratory and cardiovascular complications along with postoperative nausea and vomiting, shivering, cough grading, Aldrete score, Ramsay sedation scale, and intraoperative awareness were recorded. Statistical Analysis: Continuous variables such as HR and MAP were analyzed using analysis of variance and categorical variables were analyzed using the Chi-square test. Results: Patient demographics

  10. A COMPARISON OF TWO DIFFERENT DOSES OF DEXMEDETOMIDINE INFUSION DURING MAINTENANCE OF GENERAL ANAESTHESIA IN PATIENTS UNDERGOING SPINE SURGERIES, FUNCTIONAL ENDOSCOPIC SINUS SURGERY AND MIDDLE EAR SURGERIES

    Directory of Open Access Journals (Sweden)

    Bijay

    2016-03-01

    Full Text Available BACKGROUND This study is undertaken to compare the hemodynamic effects and reduction in the doses of volatile anaesthetics and muscle relaxants using two different doses of dexmedetomidine infusion during maintenance of anaesthesia in spine, functional endoscopic sinus surgery and middle ear surgeries. METHODS Sixty patients are randomly divided into 2 groups of 30 each. After shifting to the operation theatre baseline vitals were recorded. Anesthesia induced with thiopentone sodium and intubation done with the help of succinylcholine and maintained with oxygen, nitrous oxide and isoflurane. After 1 min of intubation, maintenance infusion of dexmedetomidine (0.4 mcg/kg/hr and 0.7 mcg/kg/hr for patients allotted in 2 separate groups was started and stopped 15 min before end of surgery. Hemodynamic parameters and any reduction in the doses of volatile anaesthetics and muscle relaxants was noted. RESULTS Dexmedetomidine infusion (0.4 mcg/kg/hr and 0.7 mcg/kg/hr in both groups reduced the requirements of muscle relaxants and volatile anaesthetics. Hemodynamic stability was better in the group receiving 0.4 mcg/kg/hr. Patients receiving 0.7 mcg/kg/hr had higher incidence of hypotension, bradycardia and delayed emergence from anaesthesia. CONCLUSION Dexmedetomidine infusion at 0.4 mcg/kg/hr during maintenance of anaesthesia in spine surgery, FESS and middle ear surgery would be good option to reduce the requirements of volatile anaesthetics, muscle relaxants and for better hemodynamic stability. OBJECTIVE OF STUDY: Primary Objective To compare and evaluate the hemodynamic effects and reduction in requirements of volatile anaesthetics and muscle relaxants with two different doses of dexmedetomidine infusion during maintenance of general anaesthesia in patients undergoing spine, FESS and middle ear surgeries.

  11. Effect of Omeprazole on the Pharmacokinetics of Rosuvastatin in Healthy Male Volunteers.

    Science.gov (United States)

    Shah, Yasar; Iqbal, Zafar; Ahmad, Lateef; Khuda, Fazli; Khan, Abad; Khan, Abbas; Khan, Muhammad Imran; Ismail

    The current study aimed at the evaluation of, in vivo, the effect of omeprazole on the pharmacokinetics of rosuvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor. Omeprazole is an acid suppressant and CYP2C9, CYP3A4, and CYP2C19 substrate and inhibitor, as well as inhibitor of transporters (like P-gp). This was a randomized, open-label, 2-period, crossover study. Healthy male volunteers (N = 20), divided into 2 groups, were given single oral doses of rosuvastatin 40 mg either alone (treatment period I) or concomitantly with omeprazole 40-mg capsule (treatment period II). Plasma concentrations of rosuvastatin (rosuva) and its metabolite N-desmethyl rosuvastatin (NDM-rosuva) were quantified by a validated liquid chromatography-tandem mass spectrometry method developed in our laboratory. An insignificant decrease (P > 0.05) has been observed in the values of maximum plasma concentrations, clearance, and half-life of rosuva, whereas an insignificant increase (P > 0.05) has been observed in the area under the plasma concentration-time curves from zero time to the last measurable concentration(Equation is included in full-text article.), that extrapolated to infinity (Equation is included in full-text article.), and mean residence time values after concomitant administration with omeprazole. Although omeprazole concomitant administration altered the pharmacokinetics of NDM-rosuva metabolite significantly, rosuva's very little metabolism (10%) suggests that these changes are of no clinical significance. Concomitant administration of omeprazole with rosuva did not alter the pharmacokinetics of rosuva in healthy volunteers. These data are consistent with other reported studies, indicating that rosuva is not a good candidate for metabolism-based drug-drug interactions. Therefore, rosuva can be administered safely along with omeprazole.

  12. Effect of High-Dose Oral Rabeprazole on Recurrent Bleeding after Endoscopic Treatment of Bleeding Peptic Ulcers

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    Hyung-Keun Kim

    2012-01-01

    Full Text Available Background. The aim of this study was to compare the effect of high-dose oral rabeprazole versus high-dose IV PPI on rebleeding after endoscopic treatment of bleeding peptic ulcers. Methods. This was a two-center, prospective, randomized, controlled trial. Patients with a high-risk bleeding peptic ulcer had endoscopic hemostasis and were randomly assigned to the high-dose oral rabeprazole group (20 mg twice daily for 72 hours or the high-dose IV omeprazole group (80 mg as a bolus injection followed by continuous infusion at 8 mg/h for 72 hours. Results. The study was stopped because of slow enrollment (total n=106. The rebleeding rates within 3 days were 3.7% (2 of 54 patients given oral rabeprazole and 1.9% (1 of 52 patients given IV omeprazole (P=1.000. The rebleeding rates after 3 days were 1.9% and 0% (P=1.000, respectively. The surgical intervention rates were 3.7% and 0% (P=0.495, and the mortality rates were 1.9% and 0% (P=1.000, respectively. Conclusions. The effect of high-dose oral rabeprazole did not differ significantly from that of high-dose IV omeprazole on rebleeding, surgical intervention, or mortality after endoscopic treatment of bleeding peptic ulcers, but this requires further evaluation.

  13. Effect of high-dose oral rabeprazole on recurrent bleeding after endoscopic treatment of bleeding peptic ulcers.

    Science.gov (United States)

    Kim, Hyung-Keun; Kim, Jin-Soo; Kim, Tae-Ho; Kim, Chang-Whan; Cho, Young-Seok; Kim, Sung-Soo; Chae, Hiun-Suk; Han, Sok-Won; Park, Yong-Wan; Son, Hye-Suk; Min, Jeong-Yo; Cho, Guen-Jong; Bag, Jung-Sun; Choi, Son-Ook

    2012-01-01

    Background. The aim of this study was to compare the effect of high-dose oral rabeprazole versus high-dose IV PPI on rebleeding after endoscopic treatment of bleeding peptic ulcers. Methods. This was a two-center, prospective, randomized, controlled trial. Patients with a high-risk bleeding peptic ulcer had endoscopic hemostasis and were randomly assigned to the high-dose oral rabeprazole group (20 mg twice daily for 72 hours) or the high-dose IV omeprazole group (80 mg as a bolus injection followed by continuous infusion at 8 mg/h for 72 hours). Results. The study was stopped because of slow enrollment (total n = 106). The rebleeding rates within 3 days were 3.7% (2 of 54 patients) given oral rabeprazole and 1.9% (1 of 52 patients) given IV omeprazole (P = 1.000). The rebleeding rates after 3 days were 1.9% and 0% (P = 1.000), respectively. The surgical intervention rates were 3.7% and 0% (P = 0.495), and the mortality rates were 1.9% and 0% (P = 1.000), respectively. Conclusions. The effect of high-dose oral rabeprazole did not differ significantly from that of high-dose IV omeprazole on rebleeding, surgical intervention, or mortality after endoscopic treatment of bleeding peptic ulcers, but this requires further evaluation.

  14. The effect of continuous low dose methylprednisolone infusion on inflammatory parameters in patients undergoing coronary artery bypass graft surgery: a randomized-controlled clinical trial.

    Directory of Open Access Journals (Sweden)

    Abbas Ghiasi

    2015-02-01

    Full Text Available This trial was performed to determine if a continuous low-dose infusion of methylprednisolone is as effective as its bolus of high-dose in reducing inflammatory response. The study was single-center, double-blinded randomized clinical trial and performed in a surgical intensive care unit of an academic hospital. In this study, 72 consecutive patients undergoing elective coronary artery bypass grafting (CABG were assigned to receive either a methylprednisolone loading dose (1mg/kg followed by continuous infusion (2mg/Kg/24 hours for 1 day (low-dose regime or a single dose of methylprednisolone (15 mg/kg before cardiopulmonary bypass (high dose regime. Serum concentrations of IL-6 and C- reactive protein (CRP were measured preoperatively and 6, 24 and 48 hours after surgery, and serum creatinine was measured before the operation and 24, 48 and 72 hours postoperatively. The measurements were then compared between the groups to evaluate the efficacy of each regimen. The basic characteristics and measurements were not different between the study groups. There was no significant difference in IL-6 and CRP elevation (P=0.52 and P=0.46, respectively. Early outcomes such as the length of stay in the intensive care unit, intubation time, changes in serum creatinine and blood glucose levels, inotropic support, insulin requirements, and rate of infection were also similar in both groups. A continuous low dose infusion of methylprednisolone was as effective as a single high dose methylprednisolone in reducing the inflammatory response after CABG with extracorporeal circulation with no significant difference in the postoperative measurements and outcomes.

  15. Re-evaluation of the regulation of omeprazole in racehorses: An evidence-based approach.

    Science.gov (United States)

    Viljanto, M; Hillyer, L; Hincks, P; Pearce, C; Paine, S W

    2018-02-22

    Medication control and doping control have been established in horse racing to ensure the integrity of the sport and the welfare of the horses. This ensures that horses do not compete under the influence of any drugs, including omeprazole, a therapeutic medication used to treat equine gastric ulcer syndrome. In this study, pharmacokinetic data were produced in equine plasma and urine following an oral administration of 4 mg/kg of generic buffered formulation of omeprazole to six Thoroughbred horses in five daily doses to determine an appropriate screening limit and detection time in equine plasma and to assess whether the current detection time of 72 hr in equine urine would be applicable when an alternative omeprazole product is administered. C max of 436-2,432 ng/ml and AUC 0-tau of 1,476-4,371 ng hr ml -1 were obtained for plasma and indicated, in conjunction with other published oral omeprazole studies, that an appropriate plasma screening limit would be 500 pg/ml with a detection time of 48 hr. Urine analysis showed that omeprazole could be detected for up to 25 hr above the previously established urine screening limit of 500 pg/ml and thus indicated that the detection time advice could be potentially reduced from 72 to 48 hr to allow more comprehensive treatment of gastric lesions. © 2018 John Wiley & Sons Ltd.

  16. A comparison of two different concentrations and infusion rates of ropivacaine in perineural infusion administered at the same total dose for analgesia after foot and ankle surgery: a randomized, double blinded, controlled study.

    Science.gov (United States)

    Bombardieri, Anna M; Maalouf, Daniel B; Kahn, Richard L; Ma, Yan; Bae, James J; Wukovits, Barbara; Lee, Andrew; Jules-Elysee, Kethy M; DE Gaudio, A Raffaele; Liguori, Gregory A

    2018-04-10

    Continuous popliteal nerve block is utilized for postoperative analgesia after foot and ankle surgery. Whether only the total dose of local anesthetic or the combination of concentration and volume determine the characteristics of a continuous popliteal nerve infusion remains currently unknown. We hypothesized a reduction of the incidence of insensate extremity in patients given ropivacaine 0.4% at 4 mL/h compared to patients given ropivacaine 0.2% at 8mL/h. Sixty-four patients scheduled for major foot and ankle surgery requiring a continuous popliteal catheter infusion for postoperative analgesia were studied. Thirty-three patients were randomized to receive a continuous popliteal nerve block with 0.2% (basal 8 mL/h) and thirty-one with 0.4% (basal 4 mL/h) ropivacaine, reaching the same total dose (16 mg/h). The primary outcome was the incidence of persistent sensory block in the distal sciatic nerve distributions in the postoperative period. Secondary outcomes were the incidence of motor block, NRS pain scores at rest in the postoperative period up to 48 hours after surgery, opioid use and related side effects, patients' satisfaction. The incidence of persistent sensory block was similar in patients given 0.2% and in patients receiving 0.4% ropivacaine. The incidence of motor block, postoperative pain scores at rest, use of oral opioids, side effects and patients' satisfaction with the quality of recovery were also similar in both groups. Our results suggest that local anesthetic total dose is the primary determinant of continuous popliteal perineural infusion effects.

  17. Perioperative very low-dose ketamine infusion actually increases the incidence of postoperative remifentanil-induced shivering-double-blind randomized trial.

    Science.gov (United States)

    Suzuki, Manzo; Osumi, Makoto; Shimada, Hiromi; Bito, Hiroyasu

    2013-12-01

    Low-dose ketamine infusion (blood concentration around 100 ng/mL) during surgery reduces the incidence of postoperative shivering after remifentanil-based anesthesia. We hypothesized that perioperative infusion of very low-dose ketamine (blood concentration around 40 ng/mL) during remifentanil-based anesthesia may also prevent the development of remifentanil-induced shivering during the 2-hour period after the end of anesthesia. Fifty female patients scheduled to undergo laparoscopic cystectomy or oophorectomy were assigned to one of two groups: (1) ketamine group, in which the patients received ketamine infusion (0.1 mg/kg/hour) from induction of anesthesia to emergence from anesthesia; and (2) control group, in which the patients received saline infusion from induction up till emergence from anesthesia. Anesthesia was induced and maintained by target-controlled infusion of propofol (estimated blood concentration: 2-4 μg/mL) and infusion of remifentanil, at 0.2-0.3 μg/kg/minute. Patients were observed for shivering from the end of anesthesia to 120 minutes after anesthesia. The time point at which the patient began to shiver was recorded and assigned to one of four time periods: at emergence, from emergence to 30 minutes after anesthesia, from 30 minutes to 60 minutes after anesthesia, and >60 minutes after anesthesia. During the 120-minute observation period, the number of patients who shivered was higher in the ketamine group than the in control group (18 vs. 8, ketamine group vs. control group, p = 0.01). The time period during which patients began to shiver was different between the two groups (1 patient, 4 patients, and 13 patients vs. 3 patients, 2 patients, and 3 patients at emergence, from emergence to 30 minutes, and from 30 minutes to 60 minutes after anesthesia, respectively; ketamine group vs. control group, p = 0.007). Intraoperative infusion of very low-dose ketamine during remifentanil-based anesthesia may increase the incidence of postoperative

  18. Beneficial effect of omeprazole in a patient with severe bronchial asthma and gastro-oesophageal reflux

    NARCIS (Netherlands)

    Depla, A. C.; Bartelsman, J. F.; Roos, C. M.; Tytgat, G. N.; Jansen, H. M.

    1988-01-01

    A 25-yr-old man suffered from severe nocturnal asthma, which was shown to be provoked by pathological gastro-oesophageal reflux. A dramatic, immediate improvement of his pulmonary condition was achieved by treatment with omeprazole after failure of other therapeutic measures, including high doses of

  19. Intraoperative Low-Dose Ketamine Infusion Reduces Acute Postoperative Pain Following Total Knee Replacement Surgery: A Prospective, Randomized Double-Blind Placebo-Controlled Trial

    International Nuclear Information System (INIS)

    Pelin Cengiz, P.; Gokcinar, D.; Karabeyoglu, I.; Topcu, H.; Cicek, G. S.; Gogus, N.

    2014-01-01

    Objective: To evaluate the effect of intraoperative low-dose ketamine with general anesthesia on postoperative pain after total knee replacement surgery. Study Design: A randomized, double-blind comparative study. Place and Duration of Study: Ankara Numune Training and Research Hospital, Turkey, from January and June 2011. Methodology: Sixty adults undergoing total knee arthroplasty were enrolled in this study. The patients were randomly allocated into two groups of equal size to receive either racemic ketamine infusion (6.25 g/kg/minute) or the same volume of saline. A visual analogue scale (VAS) was used to measure each patient's level of pain at 1, 3, 6, 12, and 24 hours after surgery. Time to first analgesic request, postoperative morphine consumption and the incidence of side effects were also recorded. Results: Low-dose ketamine infusion prolonged the time to first analgesic request. It also reduced postoperative cumulative morphine consumption at 1, 3, 6, 12, and 24 hours postsurgery (p < 0.001). Postoperative VAS scores were also significantly lower in the ketamine group than placebo, at all observation times. Incidences of side effects were similar in both study groups. Conclusion: Intraoperative continuous low-dose ketamine infusion reduced pain and postoperative analgesic consumption without affecting the incidence of side effects. (author)

  20. Randomized comparative study of intravenous infusion of three different fixed doses of milrinone in pediatric patients with pulmonary hypertension undergoing open heart surgery

    Directory of Open Access Journals (Sweden)

    Neeraj Kumar Barnwal

    2017-01-01

    Full Text Available Background: Pulmonary hypertension secondary to congenital heart disease is a common problem in pediatric patients presenting for open heart surgery. Milrinone has been shown to reduce pulmonary vascular resistance and pulmonary artery pressure in pediatric patients and neonates postcardiac surgery. We aimed to evaluate the postoperative outcome in such patients with three different fixed maintenance doses of milrinone. Methodology: Patients were randomized into three groups. All patients received fixed bolus dose of milrinone 50 μg/kg on pump during rewarming. Following this, patients in low-dose group received infusion of milrinone at the rate of 0.375 μg/kg/min, medium-dose group received 0.5 μg/kg/min, and high-dose group received 0.75 μg/kg/min over 24 h. Heart rate, mean arterial pressure (MAP, mean airway pressure (MaP, oxygenation index (OI, and central venous pressure (CVP were compared at baseline and 24 h postoperatively. Dose of inotropic requirement, duration of ventilatory support and Intensive Care Unit (ICU stay were noted. Results: MAP, MaP, OI, and CVP were comparable in all three groups postoperatively. All patients in the low-dose group required low inotropic support while 70% of patients in the high-dose group needed high inotropic support to manage episodes of hypotension (P = 0.000. Duration of ventilatory support and ICU stay in all three groups was comparable (P = 0.412, P = 0.165. Conclusion: Low-dose infusions while having a clinical impact were more beneficial in avoiding adverse events and decreasing inotropic requirement without affecting duration of ventilatory support and duration of ICU stay.

  1. Occupational contact allergy to omeprazole and ranitidine.

    Science.gov (United States)

    Herrera-Mozo, Inmaculada; Sanz-Gallen, Pere; Martí-Amengual, Gabriel

    2017-05-16

    Omeprazole is a proton pump inhibition and ranitidine is an H2 histamine receptor antagonist widely used in the treatment of gastroesophageal reflex disease, peptic ulcer disease, Zollinger-Ellison syndrome and as a protector of the gastric mucosae. We report a case of occupational contact allergy to omeprazole and ranitidine. A 48-year-old man, with no pre-existing history of atopy or lifestyle factors. He neither had any medical history of consumption of drugs such as ranitidine and omeprazole. He worked for 19 months in the pharmaceutical company that manufactured ranitidine base. He presented rash in the face and eczema on the dorsum of the hands with itching. The study by prick tests with ranitidine gave negative response. Patch testing with ranitidine base and ranitidine hydrochloride gave positive response. A month later, when the patient was asymptomatic he returned to the pharmaceutical company, being switched from this previous job to the reactor manufacturing omeprazole. A few days after that, he presented erythematous eruptions involving face and neck with itching. Prick tests, path tests and in vitro laboratories studies with omeprazole gave positives. In this case the patient presented hypersensitivity type I at omeprazole and hypersensitivity type IV at omeprazole and ranitidine. Our aportation indicates the importance of careful analysis of the occupational exposure histories of patients with the suspected type I or type IV hypersensitivity to allergens, to determine whether work exposure is the cause. Med Pr 2017;68(3):433-435. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

  2. A comparison of traditional vs. Canadian tailored prophylaxis dosing of prophylactic factor infusions in children with haemophilia A and B in a single hemophilia treatment center.

    Science.gov (United States)

    Dodd, C; Watts, R G

    2012-07-01

    Prophylactic infusion of clotting factor concentrates is a developing standard of care for individuals with haemophilia. The ideal schedule and techniques of prophylactic infusions remain incompletely defined. Our aim was to determine the optimal techniques and schedules for factor prophylaxis in paediatric patients. A retrospective electronic medical record review of all children treated with prophylactic factor infusions in a single Haemophilia Treatment Center was conducted. Comparison of traditional vs. Canadian dosing regimens and primary vs. secondary prophylaxis was made. Failure of prophylaxis was defined as the first serious bleed. A total of 58 children were identified for review. Five cases were excluded (four due to high titre inhibitors and one due to repeated non-compliance), thus there were 53 total cases: 46 with severe haemophilia, 2 with moderate haemophilia, 5 with mild haemophilia, 44 with haemophilia A and 9 with haemophilia B; 32 Traditional dosing and 21 Canadian dosing regimens. Patients on primary prophylaxis had a decreased failure rate (25%) compared to children treated with secondary prophylaxis (67%) regardless of technique of prophylaxis. When compared to a 'Traditional' factor prophylaxis schedule, the 'Canadian' tailored prophylaxis protocol was comparable with the exception of a decreased use of implanted venous devices in the 'Canadian' group. Ongoing bleeding (primarily joint bleeds) occurs with all prophylactic regimens. The lowest incidence of treatment failure was noted in children who began primary prophylaxis at a young age and before initial joint bleeds. Primary prophylaxis is superior to secondary prophylaxis regardless of dosing regimen. Traditional and Canadian dosing regimens were equivalent in outcome when measured over several years of follow-up. © 2012 Blackwell Publishing Ltd.

  3. Effects of omeprazole and aluminum hydroxide/magnesium hydroxide on riociguat absorption.

    Science.gov (United States)

    Becker, Corina; Frey, Reiner; Unger, Sigrun; Artmeier-Brandt, Ulrike; Weimann, Gerrit; Mück, Wolfgang

    2016-03-01

    Riociguat, a soluble guanylate cyclase stimulator, is a novel therapy for the treatment of pulmonary hypertension. Riociguat bioavailability is reduced in neutral versus acidic conditions and therefore may be affected by concomitant use of medications that increase gastric pH. The effect of coadministration of the proton pump inhibitor omeprazole or the antacid AlOH/MgOH on the pharmacokinetics, safety, and tolerability of riociguat 2.5 mg was characterized in two open-label, randomized, crossover studies in healthy males. In study 1, subjects pretreated for 4 days with omeprazole 40 mg received cotreatment with omeprazole plus riociguat or riociguat alone (no pretreatment) on day 5 (n = 12). In study 2, subjects received cotreatment with 10 mL AlOH/MgOH plus riociguat or riociguat alone (n = 12). Pre- and cotreatment with omeprazole decreased riociguat bioavailability (mean decreases in area under the plasma concentration-time curve [AUC] and maximum concentration in plasma [C max] were 26% and 35%, respectively). Cotreatment with AlOH/MgOH resulted in greater decreases in riociguat bioavailability (mean decreases in AUC and C max were 34% and 56%, respectively). In both studies, most adverse events (AEs) were of mild intensity, and no serious AEs were reported. No additional safety signals were identified. Treatment with riociguat, with or without omeprazole or AlOH/MgOH, was well tolerated, with a good safety profile. Owing to the resulting increase of gastric pH, riociguat bioavailability is reduced by coadministration with AlOH/MgOH and, to a lesser extent, by coadministration with omeprazole. Thus, antacids should not be administered within an hour of receiving riociguat, but no dose adjustment is required for coadministration of proton pump inhibitors.

  4. Behaviour of spectral entropy, spectral edge frequency 90%, and alpha and beta power parameters during low-dose propofol infusion.

    LENUS (Irish Health Repository)

    Mahon, P

    2012-02-03

    BACKGROUND: In this study we analyse the behaviour, potential clinical application and optimal cortical sampling location of the spectral parameters: (i) relative alpha and beta power; (ii) spectral edge frequency 90%; and (iii) spectral entropy as monitors of moderate propofol-induced sedation. METHODS: Multi-channel EEG recorded from 12 ASA 1 (American Society of Anesthesiologists physical status 1) patients during low-dose, target effect-site controlled propofol infusion was used for this analysis. The initial target effect-site concentration was 0.5 microg ml(-1) and increased at 4 min intervals in increments of 0.5 to 2 microg ml(-1). EEG parameters were calculated for 2 s epochs in the frequency ranges 0.5-32 and 0.5-47 Hz. All parameters were calculated in the channels: P4-O2, P3-O1, F4-C4, F3-C3, F3-F4, and Fp1-Fp2. Sedation was assessed clinically using the OAA\\/S (observer\\'s assessment of alertness\\/sedation) scale. RESULTS: Relative beta power and spectral entropy increased with increasing propofol effect-site concentration in both the 0.5-47 Hz [F(18, 90) = 3.455, P<0.05 and F(18, 90) = 3.33, P<0.05, respectively] and 0.5-32 Hz frequency range. This effect was significant in each individual channel (P<0.05). No effect was seen of increasing effect-site concentration on relative power in the alpha band. Averaged across all channels, spectral entropy did not outperform relative beta power in either the 0.5-32 Hz [Pk=0.79 vs 0.814 (P>0.05)] or 0.5-47 Hz range [Pk=0.81 vs 0.82 (P>0.05)]. The best performing indicator in any single channel was spectral entropy in the frequency range 0.5-47 Hz in the frontal channel F3-F4 (Pk=0.85). CONCLUSIONS: Relative beta power and spectral entropy when considered over the propofol effect-site range studied here increase in value, and correlate well with clinical assessment of sedation.

  5. Appropriateness of Omeprazole Prescribing in Quebec’s Senior Population

    Directory of Open Access Journals (Sweden)

    Jean-Pierre Grégoire

    2000-01-01

    Full Text Available BACKGROUND: Prescribing omeprazole for the treatment of digestive disorders accounts for an important part of the costs in Quebec’s drug benefit plan. In July 1993, the Quebec drug program listed omeprazole, with restriction, in its formulary. On January 1, 1994, this restriction was lifted; since then, omeprazole has been listed in the regular provincial formulary.

  6. Effects of target-controlled infusion of high-dose naloxone on pain and hyperalgesia in a human thermal injury model

    DEFF Research Database (Denmark)

    Springborg, Anders D; Jensen, Elisabeth K; Taylor, Bradley K

    2016-01-01

    injury has demonstrated reinstatement of nociceptive hypersensitivity indicating unmasking of latent sensitization. In a recent human study, pain hypersensitivity assessed as secondary hyperalgesia area (SHA), was reinstated 7 days after a mild thermal injury, in 4 out of 12 subjects after a naloxone...... infusion.The aims of the present study are first, to replicate our previous findings in a larger-sized study; second, to examine if high sensitizers (subjects presenting with large SHA after a thermal injury) develop a higher degree of hypersensitivity after naloxone challenge than low sensitizers...... (subjects presenting with restricted SHA after a thermal injury); and third to examine a dose-response relationship between 3 stable naloxone concentrations controlled by target-controlled infusion, and the unmasking of latent sensitization.Healthy participants (n = 80) underwent a screening day (day 0...

  7. High altitude-induced albuminuria in normal man is enhanced by infusion of low-dose dopamine

    DEFF Research Database (Denmark)

    Hansen, J M; Kanstrup, I L; Richalet, J P

    1996-01-01

    Renal function and the urinary excretion rate of albumin (Ualb) at rest and during infusion of dopamine (3 micrograms kg-1 min-1) were investigated in eight normal volunteers at sea level and 48 h after a rapid, passive ascent to an altitude of 4350 m. Oxygen saturation decreased to 81% (77...... increased ERPF, GFR, CLi, CNa, and decreased the filtration fraction in both environments. Infusion of dopamine further increased Ualb to 10.5 micrograms min-1 (5.5-64.8) (p

  8. To Flavor or Not to Flavor Extemporaneous Omeprazole Liquid.

    Science.gov (United States)

    Chuong, Monica C; Taglieri, Catherine A; Kerr, Stephen G

    2017-01-01

    Omeprazole is a proton pump inhibitor used to treat the symptoms of gastro esophageal reflux disease, ulcers, excess stomach acid, infection with Helicobacter pylori, and to control the gastric side effects of various drugs. The approved dosage forms in the U.S. are powder in compounding kits, delayed-release granules for oral suspension, oral delayed-release tablets, and oral delayed-release capsules. An extemporaneously compounded unsweetened oral liquid method, published in the International Journal of Pharmaceutical Compounding, was found to be commonly used by pharmacists. This project investigated the robustness of the compendium omeprazole high-performance liquid chromatographic assay in evaluating an oral liquid made from commercial delayed-release pellets, the potency of extemporaneously compounded solutions having a 1.125% v/v flavored versus unflavored samples stored at controlled cold temperatures at different time points, and examining the absorption spectrum of the flavoring agent. As part of the study, stability-indication testing was also conducted. The studies indicate that the chromatographic area under the plasma concentration-time curve of both study groups remained over 90% of the label claim during the follow-up period. The flavor did not significantly impact the pH of the oral liquid. This study further identified (1) an increase in resilient foam formation in the flavored liquid, potentially hindering dosing accuracy, (2) omeprazole is oxidized easily by 3% hydrogen peroxide, and (3) flavoring agent absorbs in an ultraviolet visible spectroscopy spectral range often used in assay detectors for quantification of drug molecules, and could interfere with assay protocols of the same. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

  9. Biliary excretion of intravenous (/sup 14/C) omeprazole in humans

    Energy Technology Data Exchange (ETDEWEB)

    Lind, T.; Andersson, T.; Skanberg, I.O.; Olbe, L.

    1987-11-01

    We have studied the biliary excretion of (/sup 14/C) omeprazole in humans. The study was performed in eight healthy subjects and the technique used was based on multiple marker dilution principles with double-lumen tubes placed in both the stomach and intestine. The results obtained show a 16% biliary excretion of (/sup 14/C) omeprazole. These data suggest a minimal spillover of omeprazole from the gastric mucosa into the gastric lumen in humans. The results also agree with previous data of the fecal recovery of radiolabeled omeprazole that suggest that the fecal excretion of intravenous omeprazole in humans is entirely accounted for by biliary excretion.

  10. Biliary excretion of intravenous [14C] omeprazole in humans

    International Nuclear Information System (INIS)

    Lind, T.; Andersson, T.; Skanberg, I.O.; Olbe, L.

    1987-01-01

    We have studied the biliary excretion of [ 14 C] omeprazole in humans. The study was performed in eight healthy subjects and the technique used was based on multiple marker dilution principles with double-lumen tubes placed in both the stomach and intestine. The results obtained show a 16% biliary excretion of [ 14 C] omeprazole. These data suggest a minimal spillover of omeprazole from the gastric mucosa into the gastric lumen in humans. The results also agree with previous data of the fecal recovery of radiolabeled omeprazole that suggest that the fecal excretion of intravenous omeprazole in humans is entirely accounted for by biliary excretion

  11. Whether preventive low dose magnesium sulphate infusion has an influence on postoperative pain perception and the level of serum beta-endorphin throughout the total abdominal hysterectomy.

    Science.gov (United States)

    Haryalchi, K; Abedinzade, M; Khanaki, K; Mansour Ghanaie, M; Mohammad Zadeh, F

    Due to the known role of preventive low dose magnesium sulphate on postoperative pain management, in this randomized, double-blinded, placebo-controlled study, we tried to investigate the possible relationship between low dose intra-operative magnesium sulphate infusion, postoperative analgesia and the level of serum beta-endorphin during total abdominal hysterectomy under general anesthesia. Forty women undergoing total abdominal hysterectomy were randomly allocated into 2 groups (20 in each arm). Fifteen minutes before induction of anaesthesia, the case group received a continuous intravenous infusion of magnesium sulphate (15mg/kg/h) and placebo control group received the same volume of isotonic saline. Pain scores were assessed at 0, 6, 12, and 24h after operations using Verbal Numeric Rating Scale. Pethidine consumption was recorded precisely. Serum level of beta-endorphin just 15min before the induction and at the end of the operations was determined by ELISA technique. At 6 and 12h after the operations, Verbal Numeric Rating Scale in the case group was significantly lower than that of placebo control group (P=.0001). Over 24h after the operations, pethidine consumption was significantly lower in the case group compared with control group (P=.0001). In the case group, serum level of beta-endorphin was significantly decreased at the end of the operations compared with before the induction (P=.04). We illustrated that preventive low dose intra-operative magnesium sulphate infusion reduces postoperative pain, has opioid sparing effect and declines serum beta-endorphin concentration during total abdominal hysterectomy. Copyright © 2017 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

  12. Computerised insulin dosing calculators for the management of continuous insulin infusions after cardiac surgery: A systematic review and meta-analysis.

    Science.gov (United States)

    Higgs, Megan H; Fernandez, Ritin S

    2017-04-01

    To investigate the effectiveness of computerised insulin dosing calculators for the management of continuous insulin infusions in adult patients who underwent cardiac surgery. A systematic review was conducted. The CINAHL, MEDLINE and Cochrane databases were searched for primary studies that compared a computerised insulin dosing calculator to a paper protocol. The main outcome measures were mean Blood Glucose Level (BGL), time to achieve BGL target range, time spent within BGL target range, the incidence of hyperglycaemia and the incidence of hypoglycaemia. Five studies were included in the final review. Pooled data demonstrated significant improvements in mean BGL (MD -14.24, 95% CI -26.93 to -1.55), p=0.03 and significantly lower rates of hypoglycaemia (OR 0.038, 95% CI: 0.16-0.90), p=0.03 amongst the computer calculator groups in comparison to the paper protocol groups. No significant difference in the incidence of severe hypoglycaemia was demonstrated (OR 0.21, 95% CI 0.02-1.79), p=0.15. No difference was found in time (hours) to reach target blood glucose range (MD -1.47, 95% CI -3.75 to 0.81), p=0.21. There is some evidence to support the use of computerised insulin dosing calculators for insulin infusion management within critical care environments. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Histopathology of the gastric oxyntic mucosa in two different patient groups during long-term treatment with omeprazole

    DEFF Research Database (Denmark)

    Hage, Esther; Hendel, Lene; Gustafsen, Jens

    2003-01-01

    of gastric mucosal inflammation, omeprazole dose, duration of treatment and acid inhibition. The level of gastrin secretion and high plasma gastrin appear to accelerate ECL cell proliferation and parietal cell changes possibly influenced by chronic gastritis and H. pylori infection.......OBJECTIVES: Hypochlorhydria, hypergastrinaemia, inflammation and Helicobacter pylori infection, dose and duration of omeprazole treatment may separately, or in combination, influence the proliferation of enterochromaffin-like (ECL) cells and parietal cell changes in gastric mucosa. To assess...... and received continuous omeprazole treatment for a mean of 7.5 and 9 years. The patients were investigated every 6-12 months with endoscopy, biopsies and histology, and plasma gastrin measurements. PSS patients were titrated by 24 h pH-metry to oesophageal pH>4, and all ZES patients were titrated to a basal...

  14. Myocardial metabolism of 123I-BMIPP under low-dose dobutamine infusion: implications for clinical SPECT imaging of ischemic heart disease

    International Nuclear Information System (INIS)

    Hosokawa, Ryohei; Fujita, Masatoshi; Kambara, Naoshige; Ohba, Muneo; Tadamura, Eiji; Kimura, Takeshi; Kita, Toru; Nohara, Ryuji; Hirai, Taku; Fujibayashi, Yasuhisa

    2005-01-01

    123 I-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid ( 123 I-BMIPP) is a fatty acid analog for single-photon emission computed tomography (SPECT) imaging that is mainly stored in the triglyceride pool. Low-dose dobutamine infusion has been reported to improve BMIPP uptake in the stunned myocardium, but the mechanism underlying this effect remains unclear. The purpose of this study was therefore to investigate the myocardial metabolism of 123 I-BMIPP in the stunned myocardium under low-dose dobutamine infusion, and to elucidate the mechanism by which dobutamine improves BMIPP uptake. Using open-chest dogs, stunned myocardium was induced by occlusion of the left anterior descending artery (LAD) for 30 min, with subsequent reperfusion (ischemia group, n=6). After direct injection of BMIPP into the LAD, myocardial extraction and retention were examined and metabolites evaluated (using high-performance liquid chromatography) during dobutamine infusion. The results in the ischemia group were compared with findings obtained in a control group under dobutamine infusion (n=6). Dobutamine infusion significantly increased both the rapid extraction (within 30 s) of BMIPP into the myocardium (control vs ischemia group: 48±19% vs 66±14%, p<0.05) and its subsequent retention (73±13% vs 85±8%, p<0.05). The metabolites from the myocardium consisted of back diffusion of nonmetabolized BMIPP, the alpha-oxidation metabolite, intermediate metabolites, and the full-oxidation metabolite. Among these metabolites, the full-oxidation metabolite decreased significantly (from 34.0±20.0% to 15.8±9.3%, p<0.05) in the stunned regions, though back diffusion of nonmetabolized BMIPP increased (from 51.3±21.9% to 71.3±10.1%, p<0.05). These results indicate that increased uptake of BMIPP in stunned myocardium is mainly due to decreased beta-oxidation in tissue and increased shunt retention of BMIPP in the triglyceride pool, and thereby provide further insight into the pathophysiology of

  15. Myocardial metabolism of {sup 123}I-BMIPP under low-dose dobutamine infusion: implications for clinical SPECT imaging of ischemic heart disease

    Energy Technology Data Exchange (ETDEWEB)

    Hosokawa, Ryohei; Fujita, Masatoshi; Kambara, Naoshige; Ohba, Muneo; Tadamura, Eiji; Kimura, Takeshi; Kita, Toru [Kyoto University Graduate School of Medicine, Department of Cardiovascular Medicine, and Nuclear Medicine, Kyoto (Japan); Nohara, Ryuji [The Tazuke Kofukai Medical Research Institute, Department of Cardiology, Kitano Hospital, Osaka (Japan); Hirai, Taku [Kinki University School of Medicine, Department of Cardiology, Nara Hospital, Nara (Japan); Fujibayashi, Yasuhisa [Fukui Medical University, Molecular Imaging, Biomedical Imaging Research Center, Fukui (Japan)

    2005-01-01

    {sup 123}I-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid ({sup 123}I-BMIPP) is a fatty acid analog for single-photon emission computed tomography (SPECT) imaging that is mainly stored in the triglyceride pool. Low-dose dobutamine infusion has been reported to improve BMIPP uptake in the stunned myocardium, but the mechanism underlying this effect remains unclear. The purpose of this study was therefore to investigate the myocardial metabolism of {sup 123}I-BMIPP in the stunned myocardium under low-dose dobutamine infusion, and to elucidate the mechanism by which dobutamine improves BMIPP uptake. Using open-chest dogs, stunned myocardium was induced by occlusion of the left anterior descending artery (LAD) for 30 min, with subsequent reperfusion (ischemia group, n=6). After direct injection of BMIPP into the LAD, myocardial extraction and retention were examined and metabolites evaluated (using high-performance liquid chromatography) during dobutamine infusion. The results in the ischemia group were compared with findings obtained in a control group under dobutamine infusion (n=6). Dobutamine infusion significantly increased both the rapid extraction (within 30 s) of BMIPP into the myocardium (control vs ischemia group: 48{+-}19% vs 66{+-}14%, p<0.05) and its subsequent retention (73{+-}13% vs 85{+-}8%, p<0.05). The metabolites from the myocardium consisted of back diffusion of nonmetabolized BMIPP, the alpha-oxidation metabolite, intermediate metabolites, and the full-oxidation metabolite. Among these metabolites, the full-oxidation metabolite decreased significantly (from 34.0{+-}20.0% to 15.8{+-}9.3%, p<0.05) in the stunned regions, though back diffusion of nonmetabolized BMIPP increased (from 51.3{+-}21.9% to 71.3{+-}10.1%, p<0.05). These results indicate that increased uptake of BMIPP in stunned myocardium is mainly due to decreased beta-oxidation in tissue and increased shunt retention of BMIPP in the triglyceride pool, and thereby provide further insight

  16. Rhabdomyolysis secondary to drug interaction between atorvastatin, omeprazole, and dexamethasone

    Directory of Open Access Journals (Sweden)

    Elazzazy S

    2012-09-01

    Full Text Available Shereen Elazzazy,1 Saad S Eziada,2 Manal Zaidan11Pharmacy Department, 2Oncology Hematology Department, National Center for Cancer Care and Research, Hamad Medical Corporation, Doha, QatarAbstract: Concomitant administration of atorvastatin, omeprazole, and dexamethasone has been shown to increase the serum concentration of serum hydroxymethylglutaryl coenzyme A which can be associated with elevation of creatine kinase and an increased risk of severe myopathy and rhabdomyolysis. In this paper, we report a case of a 60-year-old female patient with stage IV colon cancer and compromised hepatic function receiving palliative care who developed rhabdomyolysis while taking atorvastatin, omeprazole, and dexamethasone. Atorvastatin was stopped, and the dexamethasone dose was decreased. Her case was complicated by urosepsis cultures revealing an extended spectrum β-lactamase-producing strain of Escherichia coli, and she died on the second day after admission. Physicians should evaluate the risk/benefit ratio of continuing statins in palliative care patients, and pay special attention to the monitoring of patients on statins and P-glycoprotein inhibitors regardless of hepatic function.Keywords: statins, rhabdomyolysis, drug–drug interaction, P-glycoprotein inhibitors

  17. Infusion cisternography

    International Nuclear Information System (INIS)

    Magnaes, B.; Rootwelt, K.; Sjaastad, O.

    1976-01-01

    A source of error in cerebrospinal fluid (CSF) infusion tests is leakage at the dural puncture site. The addition of a bolus of radionuclide to the infusion fluid was helpful in detecting the existence of leakage as shown by increased infusion pressure in six of eight patients studied with and without scintigraphic evidence of leakage. Comparison of CSF dynamics in 26 patients studied by infusion cisternography and conventional cisternography showed similar patterns, suggesting no alteration of CSF dynamics by the artificial CSF infusion. Combining the two tests, therefore, resulted in simple identification of the leakage and saved the patient time and discomfort

  18. Catheter-Directed Thrombolysis with a Continuous Infusion of Low-Dose Urokinase for Non-Acute Deep Venous Thrombosis of the Lower Extremity

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Binbin; Zhang, Jingyong; Wu, Xuejun; Han, Zonglin; Zhou, Hua; Dong, Dianning; Jin, Xing [Shandong Provincial Hospital, Shandong University, Ji' nan (China)

    2011-02-15

    We wanted to evaluate the feasibility of catheter-directed thrombolysis with a continuous infusion of low-dose urokinase for treating non-acute (less than 14 days) deep venous thrombosis of the lower extremity. The clinical data of 110 patients who were treated by catheter-directed thrombolysis with a continuous infusion of low-dose urokinase for lower extremity deep venous thrombosis was analysed. Adjunctive angioplasty or/and stenting was performed for the residual stenosis. Venous recanalization was graded by pre- and posttreatment venography. Follow-up was performed by clinical evaluation and Doppler ultrasound. A total of 112 limbs with deep venous thrombosis with a mean symptom duration of 22.7 days (range: 15-38 days) were treated with a urokinase infusion (mean: 3.5 million IU) for a mean of 196 hours. After thrombolysis, stent placement was performed in 25 iliac vein lesions and percutaneous angioplasty (PTA) alone was done in fi ve iliac veins. Clinically significant recanalization was achieved in 81% (90 of 112) of the treated limbs: complete recanalization was achieved in 28% (31 of 112) and partial recanalization was achieved in 53% (59 of 112). Minor bleeding occurred in 14 (13%) patients, but none of the patients suffered from major bleeding or symptomatic pulmonary embolism. During followup (mean: 15.2 months, range: 3-24 months), the veins were patent in 74 (67%) limbs. Thirty seven limbs (32%) showed progression of the stenosis with luminal narrowing more than 50%, including three with rethrombosis, while one revealed an asymptomatic iliac vein occlusion: 25 limbs (22%) developed mild post-thrombotic syndrome, and none had severe post-thrombotic syndrome. Valvular reflux occurred in 24 (21%) limbs. Catheter-directed thrombolysis with a continuous infusion of low-dose urokinase combined with adjunctive iliac vein stenting is safe and effective for removal of the clot burden and for restoration of the venous flow in patients with non-acute lower

  19. Extractive Spectrophotometric Determination of Omeprazole in ...

    African Journals Online (AJOL)

    Erah

    by dilution of the stock solution. The marketed capsule of omeprazole used in the determination was Pirazole® with a labeled strength of 20 mg and manufactured by. Nicholas Piramal India Limited, Parel,. Mumbai, India. Optimisation of experimental conditions. While studying the effect of pH, the drug-dye ion-pair formation ...

  20. Intravenous form of omeprazole will be replaced by oral form in patients with ulcer bleeding

    Directory of Open Access Journals (Sweden)

    A.V. Savustyanenko

    2014-11-01

    Full Text Available The results of the research suggest the same therapeutic efficacy of oral and intravenous forms of omeprazole in patients with peptic ulcer bleeding. This formulation should be administered at a high dose (orally first dose of 80 mg and then 40 mg every 12 hours. Use of oral omeprazole is more cost-effective due to the cheaper cost of pills and the ability to discharge patients from a hospital in the earlier terms Proton pump inhibitors are more effective and more cost-effective compared to H2-blokers in patients with ulcer blee-ding. Most researchers believe that in the nearest future will be need to revise existing guidelines for the management of patients with ulcer bleeding in favor of replacing the recommendations on the use of intravenous forms of proton pump inhibitors on oral.

  1. Omeprazole blocks STAT6 binding to the eotaxin-3 promoter in eosinophilic esophagitis cells.

    Directory of Open Access Journals (Sweden)

    Xi Zhang

    Full Text Available Patients who have esophageal eosinophilia without gastroesophageal reflux disease (GERD nevertheless can respond to proton pump inhibitors (PPIs, which can have anti-inflammatory actions independent of effects on gastric acid secretion. In esophageal cell cultures, omeprazole has been reported to inhibit Th2 cytokine-stimulated expression of eotaxin-3, an eosinophil chemoattractant contributing to esophageal eosinophilia in eosinophilic esophagitis (EoE. The objective of this study was to elucidate molecular mechanisms underlying PPI inhibition of IL-4-stimulated eotaxin-3 production by esophageal cells.Telomerase-immortalized and primary cultures of esophageal squamous cells from EoE patients were treated with IL-4 in the presence or absence of acid-activated omeprazole or lansoprazole. We measured eotaxin-3 protein secretion by ELISA, mRNA expression by PCR, STAT6 phosphorylation and nuclear translocation by Western blotting, eotaxin-3 promoter activation by an exogenous reporter construct, and STAT6, RNA polymerase II, and trimethylated H3K4 binding to the endogenous eotaxin-3 promoter by ChIP assay. Omeprazole in concentrations ≥5 µM significantly decreased IL-4-stimulated eotaxin-3 protein secretion and mRNA expression. Lansoprazole also blocked eotaxin-3 protein secretion. Omeprazole had no effect on eotaxin-3 mRNA stability or on STAT6 phosphorylation and STAT6 nuclear translocation. Rather, omeprazole blocked binding of IL-4-stimulated STAT6, RNA polymerase II, and trimethylated H3K4 to the eotaxin-3 promoter.PPIs, in concentrations achieved in blood with conventional dosing, significantly inhibit IL-4-stimulated eotaxin-3 expression in EoE esophageal cells and block STAT6 binding to the promoter. These findings elucidate molecular mechanisms whereby patients with Th2 cytokine-driven esophageal eosinophilia can respond to PPIs, independent of effects on gastric acid secretion.

  2. Bismuth-Based Quadruple Therapy with Bismuth Subcitrate, Metronidazole, Tetracycline and Omeprazole in the Eradication of Helicobacter pylori

    Directory of Open Access Journals (Sweden)

    Raymond Lahaie

    2001-01-01

    Full Text Available BACKGROUND: A previous study showed that 14 days of qid bismuth-based triple therapy with tetracycline 500 mg, metronidazole 250 mg and colloidal bismuth subcitrate 120 mg resulted in excellent Helicobacter pylori eradication rates (89.5%. The present study looked at a shorter treatment period by adding omeprazole and by reducing the dose of tetracycline.

  3. Evaluation of hematologic toxicity of concurrent chemoradiotherapy using protracted infusion of low-dose cisplatin and 5-FU and radiotherapy for malignant tumors in elderly patients

    Energy Technology Data Exchange (ETDEWEB)

    Itoh, Yoshiyuki; Fuwa, Nobukazu; Matsumoto, Akira; Asano, Akiko; Sasaoka, Masahiro; Ii, Noriko; Kimura, Yasuo [Aichi Cancer Center, Nagoya (Japan). Hospital

    1999-06-01

    We evaluated the relationship between hematologic toxicity and the daily dose of CDDP or the field size of radiation in 26 patients with malignant tumors aged>70 years who underwent concurrent chemoradiotherapy consisting of infusion of low-dose CDDP and 5-FU and radiotherapy. None of the 26 patients developed Gr4 toxicity. The incidence of Gr3 toxicity was 23.1% (6/26) for leukocytes, 7.7% (2/26) for platelets, and 3.8% (1/26) for hemoglobin, being high for leukocytes. When the patients were classified into those aged 70-74 years (younger group) and those aged>75 years (older group), the incidence of Gr3 leukocyte and platelet toxicity was low in the former but high in the latter. Concerning the relationship between hematologic toxicity and the field size of radiation, the incidence of Gr3 hemoglobin, leukocyte, and platelet toxicity with a radiation field size<100 cm{sup 2} was 44% (4/9) in the older group but 0% in the younger group. In the older group, the daily CDDP dose tended to be low, and the field size of radiation tended to be small, but the incidence of hematological toxicity was high. In the younger group, the incidence of Gr2 or Gr3 toxicity increased with the daily dose of CDDP and the field size of radiation. (author)

  4. Investigation of clinical interaction between omeprazole and tacrolimus in CYP3A5 non-expressors, renal transplant recipients

    Directory of Open Access Journals (Sweden)

    Paraskevi F Katsakiori

    2010-06-01

    Full Text Available Paraskevi F Katsakiori1, Eirini P Papapetrou2, Dimitrios S Goumenos3, George C Nikiforidis4, Christodoulos S Flordellis1Departments of 1Pharmacology, 3Internal Medicine-Nephrology, 4Medical Physics, School of Medicine, University of Patras, Rion, Greece; 2Center for Cell Engineering, Molecular Pharmacology and Chemistry Program, Memorial Sloan-Kettering Cancer Center, New York, NY, USABackground: As proton pump inhibitors share CYP3A4 enzyme with tacrolimus for their hepatic elimination, they potentially affect its pharmacokinetics, most prominently in patients with CYP2C19 or CYP3A5 gene mutations. Our aim was to investigate the impact of omeprazole on tacrolimus pharmacokinetics in CYP3A5 non-expressors, kidney transplant recipients.Methods: Twelve patients (five males/seven females were observed for 175 ± 92.05 days. Omeprazole (20 mg pos was administrated for 75.83 ± 45.17 days. Immunosuppressant regimen consisted of tacrolimus (n = 12, methylprednisolone (n = 10, mycophenolate mofetil (n = 11, azathioprine (n = 1, and everolimus (n = 2. Patient’s body weight, coadministered drugs, and tacrolimus trough levels were monitored. Aspartate and alanine aminotransferase, γ-glutamyltransferase, and bilirubin were used for evaluating hepatic function. Tacrolimus kinetics were estimated with daily dose, concentration, dose adjusted concentration, and volume of distribution with and without coadministration of omeprazole. CYP3A5 genotyping was performed with PCR followed by restriction fragment length polymorphism analysis. Statistical analysis was performed with Prism 4 software (GraphPad Software, Inc.Results: No statistically significant difference was observed in tacrolimus kinetics and hepatic function during coadministration of omeprazole.Conclusion: Our results let us propose that there is no need for more frequent therapeutic drug monitoring of tacrolimus when coadministrated with omeprazole in CYP3A5 nonexpressors, though prospective

  5. Superselective intra-arterial infusion of high-dose cisplatin combined with radiation therapy for head and neck carcinoma. Experience of Yamagata University Hospital

    Energy Technology Data Exchange (ETDEWEB)

    Hamamoto, Yasushi; Niino, Keiji; Ishiyama, Hiromichi; Koike, Shuji; Hosoya, Takaaki; Aoyagi, Masaru [Yamagata Univ. (Japan). School of Medicine

    2003-03-01

    Local effectiveness and complication of superselective intra-arterial infusion of high-dose cisdiamminedichloroplatinum (CDDP) (SIC) combined with radiation therapy (RT) were investigated. Between 1998 and 2000, 18 head and neck carcinomas including 10 maxillary carcinomas (T3; 1, T4; 9), 3 oral cavity carcinomas (T2; 1, T4; 2), and 5 oropharyngeal carcinomas (T2; 2, T4; 3) were treated with SIC and RT with or without surgery. CDDP of 100-150 mg/body was administered weekly in principle for 2-9 weeks (mean: 4.9) with the simultaneous administration of sodium thiosulfate. Radiation doses ranged from 40 Gy to 70 Gy (mean: 56.8 Gy). Complete response was obtained in 7 of 10 maxillary carcinomas, 2 of 3 oral-cavity carcinomas, and 2 of 5 oropharyngeal carcinomas, respectively. When surgical intervention was performed if necessary, 2-year local control rates for maxillary carcinoma, and other carcinoma including oral-cavity carcinoma and oropharyngeal carcinoma were 80% and 63% respectively. Two-year local control rates for T4 maxillary carcinoma, and other T4 carcinoma including oral-cavity carcinoma and oropharyngeal carcinoma were 78% and 40% respectively. Two-year overall survival rates for all cases, maxillary carcinoma, and oral-cavity/oropharyngeal carcinoma were 88%, 90% and 86% respectively. All local recurrences occurred within 6 months from the initiation of treatment. The systemic toxicity of weekly SIC was comparatively mild; however, a total CDDP dose of 1,000 mg or more and/or RT of 70 Gy induced complications of local soft tissue such as mucosal ulcer and fistula. SIC combined with RT is useful to improve the local control/survival rates and to avoid the aggressive surgery for locally advanced head and neck carcinoma. A high total dose of CDDP and/or RT of a comparatively high dose may be risk factors for local soft tissue complications. (author)

  6. Usefulness of 99mTc-methoxy-iso-butyl-isonitrile myocardial single photon emission computed tomography during infusion of low-dose dobutamine and nitroglycerin. Evaluation of myocardial viability

    International Nuclear Information System (INIS)

    Yagi, Hidenori

    1995-01-01

    This study evaluated myocardial viability with 99m Tc-methoxy-iso-butyl-isonitrile (MIBI) single photon emission computed tomography (SPECT) during infusion of low-dose of dobutamine (DOB) and nitroglycerin (NTG). The subjects were 13 patients with coronary artery disease associated with wall motion abnormalities. Myocardial SPECT with MIBI was performed during infusion of NTG followed by infusion of DOB. Rest MIBI study was also performed on a separate day. The regional uptake of MIBI was visually evaluated by scoring (from 0=normal to 3=defect) in 9 regions of left ventricular wall in comparison with LVG or echocardiography data. The regional uptake of MIBI was quantitatively evaluated in 33 segments of left ventricular wall by a computer. The uptake of MIBI during infusion of both DOB and NTG was compared with that at rest study in the region of wall motion abnormalities. The mean uptake score of MIBI during infusion of both DOB and NTG and that of MIBI at rest was 1.8 and 2.1, respectively. The uptake of MIBI was significantly improved by infusion of both DOB and NTG (p<0.01). Percent of the peak activity of MIBI during infusion of both DOB and NTG and that of MIBI at rest in the region where the uptake score had been improved was 76.6±12.7% versus 74.0±13.1% (p<0.01). Percent of the peak activity of MIBI in the region where the uptake score had not been improved was 60.1±18.1% versus 60.7±18.7% (NS). Quantitative study also showed a significant improvement of MIBI uptake on the study of DOB and NTG. These results suggest that MIBI SPECT during infusion of both DOB and NTG infusion might be useful for evaluating myocardial viability. (S.Y.)

  7. Structure and function of cerebral and mesenteric resistance arteries in low-dose endotoxin-infused pregnant rats

    NARCIS (Netherlands)

    Wiegman, Marjon J; Van der Graaf, Anne Marijn; Henning, Robert H.; Zeeman, Gerda G.; Buikema, Hendrik; Faas, Marijke M.

    Objective: Since the cerebrovasculature likely plays a prominent role in the pathophysiology of eclampsia, we assessed the effects of low-dose endotoxin-induced experimental preeclampsia on the function and structure of rat posterior cerebral arteries (PCA) and mesenteric arteries (MA). Methods:

  8. Identification of new omeprazole metabolites in wastewaters and surface waters.

    NARCIS (Netherlands)

    Boix, C; Ibáñez, M.; Zamora, T.; Sancho, J.V.; Niessen, W.M.A.; Hernández, F.

    2014-01-01

    Omeprazole is one of the world-wide most consumed pharmaceuticals for treatment of gastric diseases. As opposed to other frequently used pharmaceuticals, omeprazole is scarcely detected in urban wastewaters and environmental waters. This was corroborated in a previous research, where parent

  9. Pharmacokinetics and Pharmacodynamics during Treatment with the Omeprazole 20 mg Enteric-Coated Tablet and 20 mg Capsule in Asymptomatic Duodenal Ulcer Patients

    Directory of Open Access Journals (Sweden)

    ABR Thomson

    1997-01-01

    Full Text Available This study compared the 24 h intragastric pH profile and bioavailability at repeated dosing conditions of the omeprazole 20 mg enteric-coated tablet versus the 20 mg capsule. Forty duodenal ulcer patients in asymptomatic remission completed this randomized open two-way crossover study. Omeprazole 20 mg tablets or capsules were administered for seven days in each period. A 24 h pH recording was performed before the start of treatment and on day 7 of each treatment period. Plasma concentrations of omeprazole were determined 24 h after the dose. The treatment periods were separated by two to four weeks. The difference in percentage of time with pH of at least 3 was less than 16% in favour of the tablet (not significant. The estimated mean area under the plasma concentration-time curve as well as the maximum plasma concentration (Cmax for omeprazole were 18% and 41% higher, respectively, for the tablet versus the capsule, with the latter percentage being statistically significant. The time to reach Cmax (tmax with the tablet was, on average, about 0.5 h longer than to reach the tmax of the capsule. This study indicates that the enteric-coated tablet formulation of omeprazole is biodynamically equivalent to the capsule regarding their effects on intragastric pH during repeated dosing.

  10. Betaine improves gastroprotective effects of ranitidine and omeprazole against Indomethacin-induced gastric ulcer in rats

    Directory of Open Access Journals (Sweden)

    Masoud Alirezaei

    2017-03-01

    Full Text Available Background and Aim: Antioxidant capacity of betaine has been indicated in our recent studies. Thus, we examined oral betaine as an antioxidant agent in combination with antisecretory drugs to prevent indomethacin-induced gastric damages in rats. Materials and Methods: Fifty-six adult male Sprague–Dawley rats were divided into two controls (negative and normal and five experimental groups as follows: betaine-indomethacin (Bet.-Ind., ascorbic acid-indomethacin (Asc.-Ind., omeprazole-indomethacin (Ome.-Ind., betaine-omeprazole plus indomethacin (Bet.-Ome.-Ind. and betaine-ranitidine plus indomethacin (Bet.-Ran.-Ind.. Results: The betaine pretreated groups received betaine at a dosage of 1.5% (w/w in their diet, whereas 50 mg/kg of ascorbic acid was administered orally to the Asc.-Ind., group for 15 consecutive days. After a 24 hour fast, all the groups received 48 mg/kg of indomethacin once except for normal control group. The omeprazole and ranitidine groups also received one dose of omeprazole (10 mg/kg and ranitidine (50 mg/kg, 120 minutes before receiving indomethacin. Histopathological findings indicated the gastroprotective effects of betaine and ranitidine in pretreated rats. Pretreatment by betaine and ranitidine increased significantly the ulcer index inhibition (%, in comparison with ascorbic acid and omeprazole (alone treatment. Glutathione peroxidase (GPx activity was significantly higher in the Bet.-Ran.-Ind., group as compared to the Asc.-Ind., and Ome.-Ind., treated rats. GPx activity also increased significantly in Bet.-Ind., treated rats as compared to the Asc.-Ind. group. Catalase (CAT activity was remarkably higher in the Bet.-Ran.-Ind., treated rats than the Asc.-Ind., and Ome.-Ind., groups. TBARS concentration as a lipid peroxidation marker increased significantly in Ome.-Ind., group as compared to the Bet.-Ind., and Bet.-Ran.-Ind., treated rats. Conclusion: Thus, it seems that betaine as an antioxidant agent, is able to

  11. [Is the omeprazole and amoxicillin combination useful in the treatment eradicating Helicobacter pylori in Spain?].

    Science.gov (United States)

    Gisbert, J P; Mur, M; Sainz, S; Ceña, G; Martín, C; Sainz, R; Boixeda, D; Monés, J

    1996-02-01

    To evaluate the efficiency of omeprazole (20 mg/12 h) plus amoxycillin (1 gr/12 h) in eradicating Helicobacter pylori in duodenal ulcer patients studied in four hospitals in our country. One-hundred and four patients (mean age: 49 +/- 16 years, 67% males) attended at four general hospitals in Spain, who had a duodenal ulcer demonstrated by endoscopy. These patients were infected with H. pylori demonstrated by urease test and histologic methods, and in 32 by a breath test and 18 by culture. Omeprazole 20 mg b.i.d. plus amoxycillin 1 gr b.i.d. was administered for 2 weeks. Endoscopy was repeated 1 month after completing therapy, and the aforementioned diagnostic methods were performed again. Eradication was achieved in 29% of cases (n = 30). In multiple logistic regression analysis, duration of ulcer disease was the only variable which correlated with success in H. pylori eradication (chi(2) = 7.2; p = 0.02). Additional variables (age, sex, smoking, pre-treatment with omeprazole, AINEs or H2 antagonist, ulcer size, and antral histologic gastritis) were not correlated with H. pylori eradication. Ulcer healing was demonstrated in 80% of patients (n = 83), and the healing rate was higher when eradication was achieved (97%) than in H. pylori-positive patients (73%) (p < 0.01). Compliance was good in all cases. No adverse effects were observed. [corrected] Disappointing results were obtained with omeprazole (20 mg b.i.d.) plus amoxycillin (1 gr b.i.d.) on H. pylori eradication. This combination cannot be recommended in our country at the doses employed in this study.

  12. Prevalence of Gastroesophageal Reflux in Cats During Anesthesia and Effect of Omeprazole on Gastric pH.

    Science.gov (United States)

    Garcia, R S; Belafsky, P C; Della Maggiore, A; Osborn, J M; Pypendop, B H; Pierce, T; Walker, V J; Fulton, A; Marks, S L

    2017-05-01

    Gastroesophageal reflux (GER) is poorly characterized in anesthetized cats, but can cause aspiration pneumonia, esophagitis, and esophageal stricture formation. To determine whether pre-anesthetic orally administered omeprazole increases gastric and esophageal pH and increases serum gastrin concentrations in anesthetized cats, and to determine the prevalence of GER using combined multichannel impedance and pH monitoring. Twenty-seven healthy cats undergoing elective dental procedures. Prospective, double-masked, placebo-controlled, randomized clinical trial. Cats were randomized to receive 2 PO doses of omeprazole (1.45-2.20 mg/kg) or an empty gelatin capsule placebo 18-24 hours and 4 hours before anesthetic induction. Blood for measurement of serum gastrin concentration was collected during anesthetic induction. An esophageal pH/impedance catheter was utilized to continuously measure esophageal pH and detect GER throughout anesthesia. Mean gastric pH in the cats that received omeprazole was 7.2 ± 0.4 (range, 6.6-7.8) and was significantly higher than the pH in cats that received the placebo 2.8 ± 1.0 (range, 1.3-4.1; P < .001). Omeprazole administration was not associated with a significant increase in serum gastrin concentration (P = .616). Nine of 27 cats (33.3%) had ≥1 episode of GER during anesthesia. Pre-anesthetic administration of 2 PO doses of omeprazole at a dosage of 1.45-2.20 mg/kg in cats was associated with a significant increase in gastric and esophageal pH within 24 hours, but was not associated with a significant increase in serum gastrin concentration. Prevalence of reflux events in cats during anesthesia was similar to that of dogs during anesthesia. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  13. Preformulation Studies for Generic Omeprazole Magnesium Enteric Coated Tablets

    Directory of Open Access Journals (Sweden)

    C. O. Migoha

    2015-01-01

    Full Text Available Preformulation is an important step in the rational formulation of an active pharmaceutical ingredient (API. Micromeritics properties: bulk density (BD and tapped density (TD, compressibility index (Carr’s index, Hauser’s ratio (H, and sieve analysis were performed in order to determine the best excipients to be used in the formulation development of omeprazole magnesium enteric coated tablets. Results show that omeprazole magnesium has fair flow and compressibility properties (BD 0.4 g/mL, TD 0.485 g/mL, Carr’s index 17.5%, Hauser’s ratio 1.2, and sieve analysis time 5 minutes. There were no significant drug excipient interactions except change in colour in all three conditions in the mixture of omeprazole and aerosil 200. Moisture content loss on drying in all three conditions was not constant and the changes were attributed to surrounding environment during the test time. Changes in the absorption spectra were noted in the mixture of omeprazole and water aerosil only in the visible region of 350–2500 nm. Omeprazole magnesium alone and with all excipients showed no significant changes in omeprazole concentration for a 30-day period. Omeprazole magnesium formulation complies with USP standards with regards to the fineness, flowability, and compressibility of which other excipients can be used in the formulation.

  14. Preformulation studies for generic omeprazole magnesium enteric coated tablets.

    Science.gov (United States)

    Migoha, C O; Ratansi, M; Kaale, E; Kagashe, G

    2015-01-01

    Preformulation is an important step in the rational formulation of an active pharmaceutical ingredient (API). Micromeritics properties: bulk density (BD) and tapped density (TD), compressibility index (Carr's index), Hauser's ratio (H), and sieve analysis were performed in order to determine the best excipients to be used in the formulation development of omeprazole magnesium enteric coated tablets. Results show that omeprazole magnesium has fair flow and compressibility properties (BD 0.4 g/mL, TD 0.485 g/mL, Carr's index 17.5%, Hauser's ratio 1.2, and sieve analysis time 5 minutes). There were no significant drug excipient interactions except change in colour in all three conditions in the mixture of omeprazole and aerosil 200. Moisture content loss on drying in all three conditions was not constant and the changes were attributed to surrounding environment during the test time. Changes in the absorption spectra were noted in the mixture of omeprazole and water aerosil only in the visible region of 350-2500 nm. Omeprazole magnesium alone and with all excipients showed no significant changes in omeprazole concentration for a 30-day period. Omeprazole magnesium formulation complies with USP standards with regards to the fineness, flowability, and compressibility of which other excipients can be used in the formulation.

  15. A prospective randomized, double-dummy trial comparing IV push low dose ketamine to short infusion of low dose ketamine for treatment of  pain in the ED.

    Science.gov (United States)

    Motov, Sergey; Mai, Mo; Pushkar, Illya; Likourezos, Antonios; Drapkin, Jefferson; Yasavolian, Matthew; Brady, Jason; Homel, Peter; Fromm, Christian

    2017-08-01

    Compare adverse effects and analgesic efficacy of low-dose ketamine for acute pain in the ED administered either by single intravenous push (IVP) or short infusion (SI). Patients 18-65, presenting to ED with acute abdominal, flank, or musculoskeletal pain with initial pain score≥5, were randomized to ketamine 0.3mg/kg by either IVP or SI with placebo double-dummy. Adverse effects were evaluated by Side Effects Rating Scale for Dissociative Anesthetics (SERSDA) and Richmond Agitation-Sedation Scale (RASS) at 5, 15, 30, 60, 90, and 120min post-administration; analgesic efficacy was evaluated by Numerical Rating Scale (NRS). 48 patients enrolled in the study. IVP group had higher overall rates of feeling of unreality on SERSDA scale: 92% versus 54% (difference 37.5%; p=0.008; 95% CI 9.3-59.5%). At 5min median severity of feeling of unreality was 3.0 for IVP versus 0.0 for SI (p=0.001). IVP also showed greater rates of sedation on RASS scale at 5min: median RASS -2.0 versus 0.0 (p=0.01). Decrease in mean pain scores from baseline to 15min was similar across groups: 5.2±3.53 (95% CI 3.7-6.7) for IVP; 5.75±3.48 (95% CI 4.3-7.2) for SI. There were no statistically significant differences with respect to changes in vital signs and need for rescue medication. Low-dose ketamine given as a short infusion is associated with significantly lower rates of feeling of unreality and sedation with no difference in analgesic efficacy in comparison to intravenous push. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Gaviscon® vs. omeprazole in symptomatic treatment of moderate gastroesophageal reflux. a direct comparative randomised trial

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    Pouchain Denis

    2012-02-01

    Full Text Available Abstract Background Medical management of GERD mainly uses proton pump inhibitors. Alginates also have proven efficacy. The aim of this trial was to compare short-term efficacy of an alginate (Gaviscon®, 4 × 10 mL/day and omeprazole (20 mg/day on GERD symptoms in general practice. Methods A 14-day multicentre randomised double-blind double-dummy non-inferiority trial compared Gaviscon® (4 × 10 mL/day and omeprazole (20 mg/day in patients with 2-6 day heartburn episodes weekly without alarm signals. The primary outcome was the mean time to onset of the first 24-h heartburn-free period after initial dosing. Secondary outcomes were the proportion of patients without heartburn by D7, pain relief by D7, and reduction in pain intensity by D7 and D14. Results 278 patients were recruited; 120 were included in the Gaviscon® group and 121 in the omeprazole group for the per protocol non-inferiority analysis. The mean time to onset of the first 24-h heartburn-free period after initial dosing was 2.0 (± 2.2 days for Gaviscon® and 2.0 (± 2.3 days for omeprazole (p = 0.93; mean intergroup difference was 0.01 ± 1.55 days (95% CI = -0.41 to 0.43: i.e., less than the lower limit of the 95% CI of -0.5 days predetermined to demonstrate non-inferiority. The mean number of heartburn-free days by D7 was significantly greater in the omeprazole group: 3.7 ± 2.3 days vs. 3.1 ± 2.1 (p = 0.02. On D7, overall quality of pain relief was slightly in favour of omeprazole (p = 0.049. There was no significant difference in the reduction in pain intensity between groups by D7 (p = 0.11 or D14 (p = 0.08. Tolerance and safety were good and comparable in both groups. Conclusion Gaviscon® was non-inferior to omeprazole in achieving a 24-h heartburn-free period in moderate episodic heartburn, and is a relevant effective alternative treatment in moderate GERD in primary care. Trial registration ISRCTN62203233.

  17. Chemo-radiotherapy for localized pancreatic cancer: increased dose intensity and reduced acute toxicity with concomitant radiotherapy and protracted venous infusion 5-fluorouracil

    International Nuclear Information System (INIS)

    Poen, Joseph C.; Collins, Helen L.; Niederhuber, John E.; Oberhelman, Harry A.; Vierra, Mark A.; Bastidas, Augusto J.; Young, Harvey S.; Slosberg, Edward A.; Jeffrey, Brooke R.; Longacre, Teri A.; Goffinet, Don R.

    1996-01-01

    Purpose: Although concomitant radiotherapy (RT) and bolus 5-Fluorouracil (5-FU) have been shown to improve survival in patients with resectable or locally advanced pancreatic cancer, most patients will eventually succumb to their disease. Since 1994, we have attempted to improve efficacy by administering 5-FU by protracted venous infusion (PVI). This study compares the dose intensity and acute toxicity of our current regimen utilizing 5-FU by PVI with our prior regimen of radiotherapy and bolus 5-FU. Materials and Methods: Since January, 1986, 77 patients with resectable or locally advanced adenocarcinoma of the pancreas were treated with radiation therapy. Thirteen received radiation therapy alone or a planned split-course treatment and were therefore excluded from this study. The remaining 64 patients were treated with continuous course RT and concurrent 5-FU by bolus injection for 3 days during weeks 1 and 5 (n=44) or by PVI 5-FU throughout the entire course of radiotherapy (n=20). Patients were treated on 6 or 15 MV linear accelerators with 3-4 custom shaped fields to target doses of 40-50 Gy following pancreaticoduodenectomy or 50-60 Gy for locally advanced disease. 5-FU target doses were 500 mg/m 2 for bolus injection and 200-225 mg/m 2 /day for PVI. Dose intensity was assessed for both 5-FU and radiotherapy by calculating total doses (mg/m 2 and Gy, respectively) and dose/week of treatment. The Cooperative Group Common Toxicity Scale was used to score acute hematologic and gastrointestinal toxicity. Only those endpoints which could be reliably and objectively quantified (e.g. blood counts, weight loss, treatment interruption) were evaluated. Patients with resectable and locally advanced disease were jointly and independently evaluated. Results: The patient characteristics and radiotherapy treatment techniques were similar between the two treatment groups. The mean irradiated volume was 1,323 cm 3 (95% CI: 1,210-1,436). Chemotherapy and radiotherapy dose

  18. Omeprazole exists incompatibility with a variety of drugs

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    Li-na WANG

    2014-10-01

    Full Text Available Objective: To summarize omeprazole drug compatibility taboo and ensure the safety of medication in nursing procedures. Methods: We use the method of literature review, read the published literature statistics with the name of the drug reaction, and statistical analyze by chi-square test. Results: We find out that a total of 81 kinds of drugs are incompatible with omeprazole, including 20 kinds of antibiotic medicine, P < 0.05 was statistically significant. Conclusion: There are 81 kinds of drugs incompatible with omeprazole. In order to prevent medical accidents, nurses should pay more attention to clinical nursing operation dispensing and replacing liquid.

  19. Infusão intravenosa de vasopressina causa efeitos cardiovasculares adversos dose-dependentes em cães anestesiados Infusión intravenosa de vasopresina causa efectos cardiovasculares adversos dependientes de la dosis en canes anestesiados Vasopressin intravenous infusion causes dose dependent adverse cardiovascular effects in anesthetized dogs

    Directory of Open Access Journals (Sweden)

    Luiz Cláudio Martins

    2010-02-01

    Full Text Available FUNDAMENTO: A arginina-vasopressina (AVP tem sido amplamente utilizada no tratamento do choque vasodilatador. Entretanto, há muitas questões relativas ao seu uso clínico, especialmente em altas doses, pois sua utilização pode estar associada a efeitos cardíacos adversos. OBJETIVO: Investigar os efeitos cardiovasculares da AVP em infusão IV contínua nos parâmetros hemodinâmicos em cães. MÉTODOS: Dezesseis cães saudáveis sem raça definida, anestesiados com pentobarbital, receberam um cateter intravascular e foram aleatoriamente designados para dois grupos: controle (solução salina - placebo; n=8 e AVP (n=8. O grupo do estudo recebeu infusão de AVP por três períodos consecutivos de 10 minutos a doses logaritmicamente progressivas (0,01; 0,1 e 1,0 U/kg/min, a intervalos de 20 minutos. A frequência cardíaca (HR e as pressões intravasculares foram continuamente registradas. O debito cardíaco foi medido através do método de termodiluição. RESULTADOS: Nenhum efeito hemodinâmico significante foi observado durante a infusão de 0,01 U/kg/min de AVP, mas com as doses mais altas, de 0,1 e 1,0U/kg/min, houve um aumento progressivo na pressão arterial média (PAM e índice de resistência vascular sistêmica (IRVS, com significante diminuição na frequência cardíaca (FC e índice cardíaco (IC. Com a dose de 1,0 U/kg/min, também foi observado um aumento significante no índice de resistência vascular pulmonar (IRVP, principalmente devido à diminuição no IC. CONCLUSÃO: A AVP em doses entre 0,1 e 1,0 U/kg/min resultou em significantes aumentos na PAM e no IRVS, com efeitos inotrópicos e cronotrópicos negativos em animais saudáveis. Embora essas doses sejam de 10 a 1.000 vezes maiores do que as rotineiramente utilizadas no tratamento do choque vasodilatador, nossos dados confirmam que a AVP deveria ser usada cuidadosamente e sob rígida monitoração hemodinâmica na prática clínica, especialmente se doses maiores do

  20. 0.5 mg/kg versus 1 mg/kg of intravenous omeprazole for the prophylaxis of gastrointestinal bleeding in critically ill children: a randomized study.

    Science.gov (United States)

    Solana, Maria José; López-Herce, Jesús; Sánchez, Amelia; Sánchez, César; Urbano, Javier; López, Dolores; Carrillo, Angel

    2013-04-01

    To compare the effect of 2 doses of intravenous omeprazole on gastric pH, gastrointestinal bleeding, and adverse effects in critically ill children. We undertook a prospective randomized clinical trial in critically ill children at risk of gastrointestinal bleeding. The effect of 2 intravenous omeprazole regimens (0.5 or 1 mg/kg every 12 hours) on the gastric pH and incidence of gastrointestinal hemorrhage was compared. The efficacy criteria were a gastric pH >4 and the absence of clinically significant gastrointestinal bleeding. Forty patients, 20 in each treatment group, were studied. Overall, the gastric pH was greater than 4 for 57.8% of the time, with no difference between the doses (P = .66). The percentage of time with a gastric pH > 4 increased during the study (47.8% between 0 and 24 hours vs 76% between 24 and 48 hours, P = .001); the greater dose showed a greater increase in the percentage of time with a pH > 4: between hours 24 and 48 of the study, the gastric pH was greater than 4 for 84.5% of the time with the 1 mg/kg dose and for 65.5% of the time with the 0.5 mg/kg dose (P = .036). Plasma omeprazole levels were greater with 1 mg/kg dose, but no correlation was found between omeprazole plasma levels and gastric pH. No toxic adverse effects were detected, and there was no clinically significant bleeding. Neither of the 2 omeprazole regimens achieved adequate alkalinization of the gastric pH during the first 24 hours. Between 24 and 48 hours, the 1 mg/kg dose maintained the gastric pH greater than 4 for a greater percentage of the time. Copyright © 2013 Mosby, Inc. All rights reserved.

  1. Omeprazole for Refractory Gastroesophageal Reflux Disease during Pregnancy and Lactation

    Directory of Open Access Journals (Sweden)

    John K Marshall

    1998-01-01

    Full Text Available Symptomatic gastroesophageal reflux is a common complication of pregnancy and lactation. However, the safety of many effective medical therapies, including oral proton pump inhibitors, has not been well defined. The administration of oral omeprazole to a 41-year-old female during the third trimester of pregnancy, after ranitidine and cisapride failed to control her refractory gastroesophageal reflux, is reported. No adverse fetal effects were apparent, and the patient elected to continue omeprazole therapy (20 mg/day while breastfeeding. Peak omeprazole concentrations in breast milk (58 nM, 3 h after ingestion were less than 7% of the peak serum concentration (950 nM at 4 h, indicating minimal secretion. Although omeprazole is a potentially useful therapy for refractory gastroesophageal reflux during pregnancy and lactation, further data are needed to define better its safety and efficacy.

  2. Symptomatic Improvement of Gastroduodenal Crohn’s Disease with Omeprazole

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    K Woolfson

    1992-01-01

    Full Text Available Four patients with ileal Crohn’s disease presented with abdominal pain aggravated by food, a mean weight loss of 5.5 kg (range 4 to 7 and ulceration of the antrum and/or duodenum at gastroscnpy, without radiological features of mechanical obstruction . The endoscopic and histological appearance of the ulcers was consistent with Crohn's disease. Omeprazole 40 mg daily was administered, without other drugs, and after three days of therapy patients were asymptomatic. After eight weeks of omeprazole, a mean weight gain of 6 kg (range 3 to 10 had occurred and the drug was withdrawn. One patient remained well and three patients relapsed, but all responded to long term omeprazole for up to three years. Follow-up endoscopies have indicated healing in one patient, partial healing in two patients and no change in one patient. Omeprazole may be of value in the symptomatic management of patients with gastroduodenal Crohn’s disease.

  3. The addition of omeprazole to ondansetron for treating chemotherapy-induced nausea and vomiting in pediatric cancer patients

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    Perjuangan Dapot Hamonangan Simbolon

    2018-03-01

    Full Text Available Background Chemotherapy-induced nausea and vomiting are some of the most disturbing side effects in pediatric cancer patients. The standard recommendation is the use of 5-hydroxytryptamine 3 receptor antagonist, such as ondansetron, to treat these symptoms. Despite this treatment, more than 50% of patients still experience nausea and vomiting. Objective To evaluate the effect of the addition of omeprazole to ondansetron in the treatment of chemotherapy-induced nausea and vomiting. Methods A double-blind, randomized, controlled trial was conducted at Haji Adam Malik Hospital, Medan, North Sumatera, from March to May 2016. Subjects were children aged 1 to 18 years, diagnosed with cancer, and who received intravenous chemotherapy. Patients were randomized to receive either a single dose of ondansetron (0.5 mg/kg plus placebo or ondansetron (0.5 mg/kg plus omeprazole (0.5 mg/kg. The severity of nausea and vomiting were measured using the Rhodes index of nausea, vomiting, and retching during the 24 hours after initiation of emetogenic chemotherapy. The primary outcome of efficacy was the proportion of patients who achieved complete response (lack of nausea/vomiting. Statistical analysis was performed by Chi-square and Fischer’s exact tests. Results Seventy eligible pediatric patients were randomized into two groups: 32 subjects in the ondansetron + placebo group and 38 others in the ondansetron + omeprazole group. The therapy failed in 50% (16/32 of the ondansetron + placebo group and 18.4% (7/38 of the ondansetron + omeprazole group. There was a significant difference in the clinical response between groups (P=0.01. Conclusion The addition of omeprazole to ondansetron for the treatment of chemotherapy-induced nausea and vomiting is more effective than administration of ondansetron alone.

  4. Preformulation Studies for Generic Omeprazole Magnesium Enteric Coated Tablets

    OpenAIRE

    Migoha, C. O.; Ratansi, M.; Kaale, E.; Kagashe, G.

    2015-01-01

    Preformulation is an important step in the rational formulation of an active pharmaceutical ingredient (API). Micromeritics properties: bulk density (BD) and tapped density (TD), compressibility index (Carr’s index), Hauser’s ratio (H), and sieve analysis were performed in order to determine the best excipients to be used in the formulation development of omeprazole magnesium enteric coated tablets. Results show that omeprazole magnesium has fair flow and compressibility properties (BD 0.4 g/...

  5. Severe pegaspargase hypersensitivity reaction rates (grade ≥3) with intravenous infusion vs. intramuscular injection: analysis of 54,280 doses administered to 16,534 patients on children's oncology group (COG) clinical trials.

    Science.gov (United States)

    Burke, Michael J; Devidas, Meenakshi; Maloney, Kelly; Angiolillo, Anne; Schore, Reuven; Dunsmore, Kimberly; Larsen, Eric; Mattano, Len A; Salzer, Wanda; Winter, Stuart S; Carroll, William; Winick, Naomi J; Loh, Mignon L; Raetz, Elizabeth; Hunger, Stephen P; Bleyer, Archie

    2017-11-08

    PEGylated asparaginase (pegaspargase) can be administered via intramuscular (IM) injection or intravenous (IV) infusion with a hypersensitivity reaction (HSR) incidence ranging 3-41%. We evaluated grade ≥3 HSRs when given IM vs. IV on six Children's Oncology Group (COG) leukemia trials (2003-2015) to determine differences in HSR rates. 54,280 doses were administered to 16,534 patients. Considering all doses of pegaspargase during induction, consolidation, and delayed intensification, grade ≥3 HSR rate with IM injection was 5.4% (n = 482/8981) compared to 3.2% for IV (n = 245/7553) (p rate following IM injection was 10.1% (n = 459/4534) compared to 5.0% (n = 222/4443) for IV (p rates to pegaspargase occurred less frequently with IV infusion than IM injection.

  6. Esomeprazole tablet vs omeprazole capsule in treating erosive esophagitis

    Science.gov (United States)

    Chen, Chih-Yen; Lu, Ching-Liang; Luo, Jiing-Chyuan; Chang, Full-Young; Lee, Shou-Dong; Lai, Yung-Ling

    2005-01-01

    AIM: Esomeprazole, an oral S-form of omeprazole, has been a greater acid inhibitor over omeprazole in treating acid-related diseases. Only less published data is available to confirm its efficacy for Asian people. Therefore, a perspective, double-blind, randomized comparison of esomeprazole tablets 40 mg (Nexium®) vs omeprazole capsules 20 mg (Losec®) in treating Chinese subjects with erosive/ulcerative reflux esophagitis (EE) was conducted. METHODS: A total of 48 EE patients were enrolled and randomized into two treatment groups under 8-wk therapy: 25 receiving esomeprazole, while another 23 receiving omeprazole treatment. Finally, 44 completed the whole 8-wk therapy. RESULTS: The difference in healing EE between two groups was 22.7% (72.7% vs 50.0%), not reaching significant value (P = 0.204). The median of the first time needed in relieving heartburn sensation was 1 d for both groups and the remission rates for heartburn on the 1st d after treatment were 77.3% and 65%, respectively (NS). The scores of various reflux relieving symptoms evaluated either by patients or by investigators were not different. Regarding drug safety, 28% of esomeprazole group and 26.1% of omeprazole group reported at least one episode of adverse effects, while constipation and skin dryness were the common side effects in both groups (NS). CONCLUSION: Esomeprazole 40 mg is an effective and safe drug at least comparable to omeprazole in treating Chinese EE patients. PMID:15918199

  7. A Single-dose Zoledronic Acid Infusion Prevents Antiretroviral Therapy–induced Bone Loss in Treatment-naive HIV-infected Patients: A Phase IIb Trial

    Science.gov (United States)

    Ofotokun, Ighovwerha; Titanji, Kehmia; Lahiri, Cecile D.; Vunnava, Aswani; Foster, Antonina; Sanford, Sara E.; Sheth, Anandi N.; Lennox, Jeffrey L.; Knezevic, Andrea; Ward, Laura; Easley, Kirk A.; Powers, Philip; Weitzmann, M. Neale

    2016-01-01

    Background. Human immunodeficiency virus (HIV) infection and antiretroviral therapy (ART) are associated with bone loss leading to increased fracture rate among HIV-infected individuals. ART-induced bone loss is most intense within the first 48 weeks of therapy, providing a window for prophylaxis with long-acting antiresorptives. Methods. In a phase 2, double-blind, placebo-controlled trial, we randomized 63 nonosteoporotic, ART-naive adults with HIV initiating ART with atazanavir/ritonavir + tenofovir/emtricitabine to a single zoledronic acid (ZOL) infusion (5 mg) vs placebo to determine the efficacy of ZOL in mitigating ART-induced bone loss. Plasma bone turnover markers and bone mineral density (BMD) were performed at weeks 0, 12, 24, and 48 weeks. Primary outcome was change in C-terminal telopeptide of collagen at 24 weeks. Repeated-measures analyses using mixed linear models were used to estimate and compare study endpoints. Results. The ZOL arm had a 65% reduction in bone resorption relative to the placebo arm at 24 weeks (0.117 ng/mL vs 0.338 ng/mL; P < .001). This effect of ZOL occurred as early as 12 weeks (73% reduction; P < .001) and persisted through week 48 (57% reduction; P < .001). The ZOL arm had an 8% higher lumbar spine BMD at 12 weeks relative to the placebo arm (P = .003), and remained 11% higher at 24 and 48 weeks. Similar trends were observed in the hip and femoral neck. Conclusions. A single dose of ZOL administered at ART initiation prevented ART-induced bone loss through the first 48 weeks of ART, the period when ART-induced bone loss is most pronounced. Validation of these results in larger multicenter randomized clinical trials is warranted. Clinical Trials Registration. NCT01228318. PMID:27193748

  8. Prophylactic therapy with omeprazole for prevention of Equine Gastric Ulcer Syndrome (EGUS) in horses in active training: A meta-analysis.

    Science.gov (United States)

    Mason, L V; Moroney, J R; Mason, R J

    2018-04-17

    Guidelines regarding the impact and value of prophylaxis or maintenance therapy in Equine Gastric Ulcer Syndrome (EGUS) are not well established or defined. The merits and the magnitude of effects of prophylaxis for spontaneous or recurrent squamous gastric ulceration in horses in training are uncertain. To pool data from randomised controlled trials (RCTs) to eliminate reporting bias and evaluate the efficacy of prophylactic omeprazole in the prevention of EGUS in training horses, and secondarily to compare prophylactic dosages of omeprazole. Meta-analysis. This meta-analysis was conducted according to the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A systematic literature search identified RCTs comparing omeprazole prophylaxis with sham in prevention of EGUS. Data were analysed using the Mantel-Haenszel test method to calculate risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CIs). Primary outcome was efficacy of prophylaxis. Secondary outcome was endoscopic severity of ulceration. The influence of study characteristics on the outcomes was examined by subgroup analyses. In preventing gastric ulcer occurrence, omeprazole prophylaxis was superior to sham in training horses (7 trials, 566 horses, RR 0.28, 95% CI 0.18 to 0.43; 23.4% in omeprazole prophylaxis versus 77.2% in sham; high quality evidence). Prevalence of ulceration was 75.3% and 87.2% in the sham arms of the 1 mg/kg and 2 mg/kg omeprazole groups, respectively. Severity scores were significantly lower for omeprazole versus sham (mean difference [MD] -1.05; 95% CI -1.35 to -0.69). Subgroup analyses comparing prophylactic omeprazole dosages resulted in a mean difference of -0.94 and -1.60 for the 1 mg/kg and 2 mg/kg groups, respectively. Studies showed heterogeneity with regard to prophylactic dose. Omeprazole prophylaxis in active training horses significantly reduces gastric ulceration compared with no prophylaxis

  9. A phase 1 randomized study evaluating the effect of omeprazole on the pharmacokinetics of a novel 5-hydroxytryptamine receptor 4 agonist, revexepride (SSP-002358, in healthy adults

    Directory of Open Access Journals (Sweden)

    Pierce D

    2015-02-01

    Full Text Available David Pierce,1 Mary Corcoran,2 Maria Velinova,3 Stuart Hossack,4 Mieke Hoppenbrouwers,5 Patrick Martin,21Shire, Basingstoke, UK; 2Shire, Wayne, PA, USA; 3PRA International, Zuidlaren, the Netherlands; 4Covance, Leeds, UK; 5Shire-Movetis NV, Turnhout, BelgiumBackground: About 30% of patients with gastroesophageal reflux disease continue to experience symptoms despite treatment with proton pump inhibitors. The 5-hydroxytryptamine 4 receptor agonist revexepride (SSP-002358 is a novel prokinetic that stimulates gastrointestinal motility, which has been suggested as a continued cause of symptoms in these patients. The aim of this study was to assess whether revexepride pharmacokinetics were affected by co-administration of omeprazole, in preparation for a proof-of-concept evaluation of revexepride added to proton pump inhibitor treatment.Methods: In this phase 1, open-label, randomized, two-period crossover study, healthy adults aged 18–55 years were given a single dose of revexepride 1 mg or revexepride 1 mg + omeprazole 40 mg. Pharmacokinetic parameters were assessed for up to 48 hours after administration of the investigational product. Adverse events, clinical chemistry and hematology parameters, electrocardiograms, and vital signs were monitored.Results: In total, 42 participants were enrolled and 40 completed the study. The median age was 24 years (18–54 years, 55% were women and 93% were white. The pharmacokinetic parameters of revexepride were similar without or with omeprazole co-administration. The mean area under the plasma concentration–time curve from time 0 to infinity (AUC0–∞ was 23.3 ng · h/mL (standard deviation [SD]: 6.33 ng · h/mL versus 24.6 ng · h/mL (SD: 6.31 ng · h/mL, and maximum plasma concentrations (Cmax were 3.89 ng/mL (SD: 1.30 ng/mL and 4.12 ng/mL (SD: 1.29 ng/mL in participants without and with omeprazole, respectively. For AUC0–∞ and Cmax, the 90% confidence intervals for the ratios of geometric least

  10. The Relative Bioavailability, Food Effect, and Drug Interaction With Omeprazole of Momelotinib Tablet Formulation in Healthy Subjects.

    Science.gov (United States)

    Xin, Yan; Shao, Lixin; Maltzman, Julie; Stefanidis, Dimitrios; Hemenway, Jeffrey; Tarnowski, Thomas; Deng, Wei; Silverman, Jeffrey A

    2018-03-01

    Momelotinib is a potent and selective small-molecule inhibitor of JAK1/2 that is under investigation for the treatment of myeloproliferative neoplasms. In a phase 1/2 study in myelofibrosis patients, once-daily dosing of a 300-mg momelotinib capsule was selected for further development based on a favorable benefit:risk profile. A tablet formulation was recently developed for further clinical evaluation. In this study, the relative bioavailability of the tablet formulation versus the initial capsule formulation and the effect of food and omeprazole on the pharmacokinetics of a single-dose momelotinib tablet were evaluated in healthy subjects. The momelotinib tablet, 200 mg, provided plasma exposure equivalent to the 300-mg capsule. Plasma exposure of momelotinib increased less than dose-proportionally from 100 to 800 mg. Food intake modestly increased C max (38% and 28% increase for low- and high-fat meals, respectively) and AUC inf (16% and 28% increase for low- and high-fat meals, respectively) for the momelotinib tablet. Omeprazole reduced the exposure of the momelotinib tablet by 36% for C max and 33% for AUC inf . Neither the food effect nor the omeprazole effect on momelotinib exposure was considered clinically meaningful because of the safety and efficacy profile of momelotinib. © 2017, The American College of Clinical Pharmacology.

  11. Triple therapy with clarithromycin, amoxicillin and omeprazole for Helicobacter pylori eradication in children and adolescents

    Directory of Open Access Journals (Sweden)

    KAWAKAMI Elisabete

    2001-01-01

    Full Text Available Background - Helicobacter pylori infection presents high prevalence in developing countries, but there are few pediatric assays evaluating antimicrobial treatment. Objective - The aim of this study was to investigate Helicobacter pylori eradication rate using a short regimen (7 and 10 days of triple therapy with clarithromycin, amoxicillin and omeprazole. Patients and methods - Twenty-five Hp positive patients who presented severe epigastralgia, were submitted to antimicrobial treatment with amoxicillin (50 mg/kg/day - maximum dose 1g bid, clarithromycin (30 mg/kg/day - maximum dose 500 mg bid and omeprazole (0.6 mg/kg/day - maximum dose 20 mg bid during 7 or 10 days. After 2 months, clinical symptoms were evaluated and gastric biopsies were taken to test Hp eradication. Results - Overall eradication rate was achieved in 16/25 patients (64% - IC(95% = 45-83%, in 11/15 (73% - IC(95% = 51-95% patients who used 10 days therapy course and in 5/10 (50% - IC(95% = 19-81% who used 7 days therapy course. Eradication drugs were well accepted and adverse effects were reported in two patients (8%. Conclusions - This triple therapy regimen had moderate efficacy (64%. The data suggests that 10 days therapy course achieves better eradication rate (73% than 7 days course (50% to treat Hp infection in our population.

  12. Acid-base chemistry of omeprazole in aqueous solutions

    International Nuclear Information System (INIS)

    Yang Rong; Schulman, Stephen G.; Zavala, Pedro J.

    2003-01-01

    Omeprazole is a potent anti-acid drug. Its absorption and mode of action are closely related to its prototropic behavior. In the present study, omeprazole samples from different sources and in different forms were studied spectrophotometrically to obtain pK a values. In the neutral to alkaline pH region, two consistent pK a values of 7.1 and 14.7 were obtained from various samples. The assignment of these pK a values was realized by comparison with the prototropic properties of N(1)-methylated omeprazole substituted on the nitrogen at the 1-position of the benzimidazole ring, which was found to have a pK a of 7.5. The omeprazole pK a of 14.7 is assigned to the dissociation of the hydrogen from the 1-position of the benzimidazole ring and the pK a of 7.1 is assigned to the dissociation from the protonated pyridine nitrogen of omeprazole. The results presented are at variance with those of earlier work

  13. Acid-base chemistry of omeprazole in aqueous solutions

    Energy Technology Data Exchange (ETDEWEB)

    Yang Rong; Schulman, Stephen G.; Zavala, Pedro J

    2003-03-28

    Omeprazole is a potent anti-acid drug. Its absorption and mode of action are closely related to its prototropic behavior. In the present study, omeprazole samples from different sources and in different forms were studied spectrophotometrically to obtain pK{sub a} values. In the neutral to alkaline pH region, two consistent pK{sub a} values of 7.1 and 14.7 were obtained from various samples. The assignment of these pK{sub a} values was realized by comparison with the prototropic properties of N(1)-methylated omeprazole substituted on the nitrogen at the 1-position of the benzimidazole ring, which was found to have a pK{sub a} of 7.5. The omeprazole pK{sub a} of 14.7 is assigned to the dissociation of the hydrogen from the 1-position of the benzimidazole ring and the pK{sub a} of 7.1 is assigned to the dissociation from the protonated pyridine nitrogen of omeprazole. The results presented are at variance with those of earlier work.

  14. Omeprazole, other antiulcer drugs and newly diagnosed gout

    Science.gov (United States)

    Meier, Christoph R.; Jick, Hershel

    1997-01-01

    Aims Case-reports describing patients who developed a first episode of acute gout while being treated with the proton pump inhibitor omeprazole led us to compare incidence rates of newly diagnosed gout cases among omeprazole, ranitidine and cimetidine users. Methods We conducted a cohort study with a nested case-control analysis using the UK-based General Practitioner Research Database (GPRD). The study encompassed a cohort of more than 53 000 subjects who received some 185 000 prescriptions for the three study drugs. Results Neither current omeprazole vs recent use (age- and sex-adjusted relative risk 1.1, 95% CI 0.5–2.1), nor current omeprazole use in comparison with current use of the two histamine H2-receptor blockers was associated with an increased risk of developing newly diagnosed gout. Higher age (RR 2.4, 95% CI 1.5–3.9), male gender (RR 5.4, 95% CI 2.8–10.3), high body mass index (OR 3.3, 95% CI 1.0–10.9) and hypertension (OR 4.5, 95% CI 1.6–12.9) were all important risk factors for gout. Conclusions While other known risk factors were significantly associated with gout, current omeprazole use was not materially associated with an increased gout incidence. PMID:9278205

  15. Spectroscopic Characterization of Omeprazole and Its Salts

    Directory of Open Access Journals (Sweden)

    Tomislav Vrbanec

    2017-01-01

    Full Text Available During drug development, it is important to have a suitable crystalline form of the active pharmaceutical ingredient (API. Mostly, the basic options originate in the form of free base, acid, or salt. Substances that are stable only within a certain pH range are a challenge for the formulation. For the prazoles, which are known to be sensitive to degradation in an acid environment, the formulation is stabilized with alkaline additives or with the application of API formulated as basic salts. Therefore, preparation and characterization of basic salts are needed to monitor any possible salinization of free molecules. We synthesized salts of omeprazole from the group of alkali metals (Li, Na, and K and alkaline earth metals (Mg, Ca. The purpose of the presented work is to demonstrate the applicability of vibrational spectroscopy to discriminate between the OMP and OMP-salt molecules. For this reason, the physicochemical properties of 5 salts were probed using infrared and Raman spectroscopy, NMR, TG, DSC, and theoretical calculation of vibrational frequencies. We found out that vibrational spectroscopy serves as an applicable spectroscopic tool which enables an accurate, quick, and nondestructive way to determine the characteristic of OMP and its salts.

  16. High-dose fast infusion of parenteral iron isomaltoside is efficacious in inflammatory bowel disease patients with iron-deficiency anaemia without profound changes in phosphate or fibroblast growth factor 23

    Science.gov (United States)

    Dahlerup, Jens Frederik; Jacobsen, Bent A.; van der Woude, Janneke; Bark, Lars-Åke; Thomsen, Lars L.; Lindgren, Stefan

    2016-01-01

    Abstract Objective: Iron isomaltoside (Monofer®) is a high-dose intravenous iron preparation with good tolerability and efficacy in inflammatory bowel disease (IBD) patients with iron deficiency anaemia (IDA). This trial evaluates the safety and efficacy, including effect on intact fibroblast growth factor 23 (iFGF23) of a high single dose and cumulative doses of iron isomaltoside in IBD patients with IDA. Materials and methods: The trial was a prospective, open-label, multi-centre trial conducted in IBD patients with IDA. Based upon haemoglobin (Hb) levels at baseline and weight, the patients received 1500, 2000, 2500 or 3000 mg of iron isomaltoside infused in single doses up to 2000 mg. The outcome measurements included adverse drug reactions (ADRs) and changes in haematology and biochemistry parameters. Results: Twenty-one IBD patients with IDA were enrolled, receiving 1500 (seven patients), 2000 (eight patients), 2500 mg (four patients) or 3000 (two patients) mg of iron. No serious ADRs were observed. Four patients experienced nine mild to moderate ADRs (hypersensitivity, pyrexia, vomiting, constipation, abdominal pain, dyspepsia (two events) and eye allergy (two events)). In total, 15 (75%) patients had an increase in Hb of ≥2.0 g/dL during the trial, with normalisation of ferritin. No changes in iFGF23 or clinically significant hypophosphataemia were found. Conclusion: Rapid infusions of high-dose iron isomaltoside, administered as single doses up to 2000 mg and cumulative doses up to 3000 mg, were without safety concerns and were efficacious in increasing Hb levels in IBD patients. Iron isomaltoside did not induce profound phosphate wasting via increased iFGF23 levels. PMID:27326766

  17. The preparation of 14C, 35S and 13C labelled forms of omeprazole

    International Nuclear Information System (INIS)

    Crowe, A.M.; Ife, R.J.; Mitchell, M.B.; Saunders, D.

    1986-01-01

    The syntheses of [benzimidazole-2- 14 C]omeprazole, [benzimidazole-2- 13 C]omeprazole, [ 35 S]omeprazole and [2-pyridyl- 14 C-methyl]-omeprazole are described. The first three compounds were prepared from the appropriate isotopically labelled carbon disulphide. The key step in the synthesis of [2-pyridyl- 14 C-methyl]omeprazole is nucleophilic alkylation of a l-ethoxypyridinium salt using [ 14 C]methyl magnesium idodide. This is the first time that a reaction of this type has been used to prepare a 2-[methyl- 14 C]methylpyridine. (author)

  18. Preparation of /sup 14/C, /sup 35/S and /sup 13/C labelled forms of omeprazole

    Energy Technology Data Exchange (ETDEWEB)

    Crowe, A.M.; Ife, R.J.; Mitchell, M.B.; Saunders, D.

    1986-01-01

    The syntheses of (benzimidazole-2- /sup 14/C)omeprazole, (benzimidazole-2-/sup 13/C)omeprazole, (/sup 35/S)omeprazole and (2-pyridyl- /sup 14/C-methyl)-omeprazole are described. The first three compounds were prepared from the appropriate isotopically labelled carbon disulphide. The key step in the synthesis of (2-pyridyl- /sup 14/C-methyl)omeprazole is nucleophilic alkylation of a l-ethoxypyridinium salt using (/sup 14/C)methyl magnesium idodide. This is the first time that a reaction of this type has been used to prepare a 2-(methyl-/sup 14/C)methylpyridine.

  19. When omeprazole met with asymptomatic Clostridium difficile colonization in a postoperative colon cancer patient: A case report.

    Science.gov (United States)

    Li, Boyu; Ma, Huachong; Wang, Zhenjun; Liu, Lihong

    2017-12-01

    Clostridium difficile infection (CDI) is a symptomatic infection due to the spore-forming bacterium, C. difficile. Asymptomatic C. difficile colonization is the stage in absence of symptoms, with a prevalence of 1.4% to 21% on hospital admission. Proton-pump inhibitors (PPIs) was implicated as a novel potential contributor to CDI. PPIs injection could make asymptomatic C. difficile colonization progress to C. difficile associated diarrhea (CDAD). A postoperative colon cancer patient, who had been taking omeprazole for 4 years after operation, got asymptomatic C. difficile colonization. When he developed clinical symptoms of digestive tract, tumor recurrence was first suspected and intravenous omeprazole was prescribed, which ultimately led to progression to symptomatic CDI. In this report, we tell the confusing differential diagnosis of cancer-associated diseases and CDAD, and discuss the possibility of solving the PPIs overuse problem by making clinical pathway of PPIs use in Chinese hospitals. CDAD, incomplete intestinal obstruction, postoperation of colon cancer. Electrolyte replacement and rehydration. Parenteral nutrition support. Omeprazole was prescribed but withdrawn later, and oral vancomycin was given at a dose of 0.25 g 4 times per day for 10 days. Diarrhea was resolved, so long as the acid reflux and vomiting. We have 2 lessons here: Be aware of PPIs induced CDI, especially the asymptomatic C. difficile colonization. Making clinical pathway specified on PPIs use by pharmacists could be a practical way to solve the problem of PPIs overuse.

  20. Improvement effect on the depth-dose distribution by CSF drainage and air infusion of a tumour-removed cavity in boron neutron capture therapy for malignant brain tumours

    Energy Technology Data Exchange (ETDEWEB)

    Sakurai, Yoshinori [Kyoto University Research Reactor Institute, Asashironishi 2-1010, Kumatori-cho, Sennan-gun, Osaka 590-0494 (Japan); Ono, Koji [Kyoto University Research Reactor Institute, Asashironishi 2-1010, Kumatori-cho, Sennan-gun, Osaka 590-0494 (Japan); Miyatake, Shin-ichi [Department of Neurosurgery, Osaka Medical College, Daigaku-cho 2-7, Takatsuki City, Osaka 569-8686 (Japan); Maruhashi, Akira [Kyoto University Research Reactor Institute, Asashironishi 2-1010, Kumatori-cho, Sennan-gun, Osaka 590-0494 (Japan)

    2006-03-07

    Boron neutron capture therapy (BNCT) without craniotomy for malignant brain tumours was started using an epi-thermal neutron beam at the Kyoto University Reactor in June 2002. We have tried some techniques to overcome the treatable-depth limit in BNCT. One of the effective techniques is void formation utilizing a tumour-removed cavity. The tumorous part is removed by craniotomy about 1 week before a BNCT treatment in our protocol. Just before the BNCT irradiation, the cerebro-spinal fluid (CSF) in the tumour-removed cavity is drained out, air is infused to the cavity and then the void is made. This void improves the neutron penetration, and the thermal neutron flux at depth increases. The phantom experiments and survey simulations modelling the CSF drainage and air infusion of the tumour-removed cavity were performed for the size and shape of the void. The advantage of the CSF drainage and air infusion is confirmed for the improvement in the depth-dose distribution. From the parametric surveys, it was confirmed that the cavity volume had good correlation with the improvement effect, and the larger effect was expected as the cavity volume was larger.

  1. Omeprazole Inhibits Cell Proliferation and Induces G0/G1 Cell Cycle Arrest through Up-regulating miR-203a-3p Expression in Barrett’s Esophagus Cells

    Directory of Open Access Journals (Sweden)

    Yichao Hou

    2018-01-01

    Full Text Available Existing data suggest that proton pump inhibitors (PPIs, particularly omeprazole, have significant anti-tumor action in monotherapy and or combination chemotherapy. Hedgehog (Hh signaling pathway represents a leading candidate as a molecular mediator of Barrett’s esophagus (BE. Studies have indicated reduced miRNAs in BE progression, however, little is known about the latent anti-neoplasm effects of miRNAs in BE cells. Here, we investigated whether omeprazole could inhibit BE progression by regulating Hh pathway and explored the promising Hh-targeted miRNAs in BE cells. We conducted qRT-PCR and immunoblotting assay to evaluate the effects of omeprazole on the expression of Hh signaling components and miR-203a-3p in CP-A and CP-B cells. The promising target genes of miR-203a-3p were predicted by bioinformatics methods, and verified by luciferase assays and qRT-PCR. The effects of omeprazole on BE cell proliferation and cell cycle distribution were determined. The overexpression or silencing of miR-203a-3p was performed to test its anti-proliferative effects. Finally, rescue experiments that miR-203a-3p inhibitor alleviated the effects of omeprazole on decreasing the levels of Gli1 mRNA, protein and luciferase were performed. Mechanistic studies showed that omeprazole could inhibit the expression of Gli1 and the nuclear localization of Gli1. Moreover, we determined that omeprazole could selectively up-regulated the expression of miR-203a-3p, and Gli1 was a bona fide target of miR-203a-3p. miR-203a-3p inhibitor alleviated the suppressing effects of omeprazole on Gli1 luciferase activity, mRNA and protein level. The functional assay suggested that omeprazole could dose-dependently inhibit BE cell growth and induce cell cycle arrest in G0/G1 phase. Additionally, overexpression and silencing of miR-203a-3p in BE cells disrupted cell cycle progress, resulting in suppressing and accelerating cell proliferation, respectively. Taken together, these data

  2. Omeprazole Inhibits Cell Proliferation and Induces G0/G1 Cell Cycle Arrest through Up-regulating miR-203a-3p Expression in Barrett's Esophagus Cells.

    Science.gov (United States)

    Hou, Yichao; Hu, Qiang; Huang, Jiao; Xiong, Hua

    2017-01-01

    Existing data suggest that proton pump inhibitors (PPIs), particularly omeprazole, have significant anti-tumor action in monotherapy and or combination chemotherapy. Hedgehog (Hh) signaling pathway represents a leading candidate as a molecular mediator of Barrett's esophagus (BE). Studies have indicated reduced miRNAs in BE progression, however, little is known about the latent anti-neoplasm effects of miRNAs in BE cells. Here, we investigated whether omeprazole could inhibit BE progression by regulating Hh pathway and explored the promising Hh-targeted miRNAs in BE cells. We conducted qRT-PCR and immunoblotting assay to evaluate the effects of omeprazole on the expression of Hh signaling components and miR-203a-3p in CP-A and CP-B cells. The promising target genes of miR-203a-3p were predicted by bioinformatics methods, and verified by luciferase assays and qRT-PCR. The effects of omeprazole on BE cell proliferation and cell cycle distribution were determined. The overexpression or silencing of miR-203a-3p was performed to test its anti-proliferative effects. Finally, rescue experiments that miR-203a-3p inhibitor alleviated the effects of omeprazole on decreasing the levels of Gli1 mRNA, protein and luciferase were performed. Mechanistic studies showed that omeprazole could inhibit the expression of Gli1 and the nuclear localization of Gli1. Moreover, we determined that omeprazole could selectively up-regulated the expression of miR-203a-3p, and Gli1 was a bona fide target of miR-203a-3p. miR-203a-3p inhibitor alleviated the suppressing effects of omeprazole on Gli1 luciferase activity, mRNA and protein level. The functional assay suggested that omeprazole could dose-dependently inhibit BE cell growth and induce cell cycle arrest in G0/G1 phase. Additionally, overexpression and silencing of miR-203a-3p in BE cells disrupted cell cycle progress, resulting in suppressing and accelerating cell proliferation, respectively. Taken together, these data provide a novel

  3. Omeprazole Absorption and Fasting Gastrinemia After Roux-en-Y Gastric Bypass.

    Science.gov (United States)

    Collares-Pelizaro, Renata V A; Santos, José S; Nonino, Carla B; Gaitani, Cristiane M; Salgado, Wilson

    2017-09-01

    Roux-en-Y gastric bypass (RYGB) is one of the bariatric surgeries most frequently performed worldwide. Since this operation may predispose to the formation of peptic ulcer of the gastrojejunal anastomosis, the use of proton pump inhibitors (PPI) is recommended during the first postoperative year. However, so far, there is no detailed knowledge about the absorption of this medication during the immediate postoperative period and consequently about its effectiveness in blocking acid secretion. The objective was to assess the possible endoscopic peptic changes, the absorption of omeprazole (OME), and the status of fasting gastrinemia before and after RYGB operation. OME absorption, the production of its metabolites omeprazole sulfone (OMES) and 5-hydroxyomeprazole (HOME), and basal (fasting) gastrinemia were determined in patients submitted to RYGB before and 2 months after the operation. Upper digestive endoscopy (UDE) was also performed before and 6 months after the operation. Twenty patients were studied. Preoperatively, all these patients had some peptic changes and 55% tested positive for Helicobacter pylori. Six months after surgery, ten patients still showed endoscopic changes and one patient tested positive for H. pylori. During the postoperative period, there was a reduction of OME absorption and of the production of its metabolites 90 min after administration of the drug, and reduction of serum gastrin levels. The standard OME dose (40 mg) administered after bariatric surgery is insufficient to achieve serum levels that can effectively block the production of hydrochloric acid, permitting the formation of peptic injuries in many patients.

  4. Phenobarbital Treatment at a Neonatal Age Results in Decreased Efficacy of Omeprazole in Adult Mice.

    Science.gov (United States)

    Tien, Yun-Chen; Piekos, Stephanie C; Pope, Chad; Zhong, Xiao-Bo

    2017-03-01

    Drug-drug interactions (DDIs) occur when the action of one drug interferes with or alters the activity of another drug taken concomitantly. This can lead to decreased drug efficacy or increased toxicity. Because of DDIs, physicians in the clinical practice attempt to avoid potential interactions when multiple drugs are coadministrated; however, there is still a large knowledge gap in understanding how drugs taken in the past can contribute to DDIs in the future. The goal of this study was to investigate the consequence of neonatal drug exposure on efficacy of other drugs administered up through adult life. We selected a mouse model to test phenobarbital exposure at a neonatal age and its impact on efficacy of omeprazole in adult life. The results of our experiment show an observed decrease in omeprazole's ability to raise gastric pH in adult mice that received single or multiple doses of phenobarbital at a neonatal age. This effect may be associated with the permanent induction of cytochrome P450 enzymes in adult liver after neonatal phenobarbital treatment. Our data indicates that DDIs may result from drugs administered in the past in an animal model and should prompt re-evaluation of how DDIs are viewed and how to avoid long-term DDIs in clinical practice. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

  5. Higher infused CD34+ cell dose and overall survival in patients undergoing in vivo T-cell depleted, but not t-cell repleted, allogeneic peripheral blood hematopoietic cell transplantation.

    Science.gov (United States)

    Kanate, Abraham Sebastian; Craig, Michael; Cumpston, Aaron; Saad, Ayman; Hobbs, Gerry; Leadmon, Sonia; Bunner, Pamela; Watkins, Kathy; Bulian, Deirdre; Gibson, Laura; Abraham, Jame; Remick, Scott C; Hamadani, Mehdi

    2011-01-01

    Understanding the effect of cellular graft composition on allogeneic hematopoietic cell transplantation (AHCT) outcomes is an area of great interest. The objective of the study was to analyze the correlation between transplant-related outcomes and administered CD34+, CD3+, CD4+ and CD8+ cell doses in patients who had undergone peripheral blood, AHCT and received either in vivo T-cell depleted or T-cell replete allografts. Comparison of consecutive patients who underwent peripheral blood AHCT in our institution between January 2003 and December 2009. The cohort of 149 patients was divided into two groups; non T-cell depleted (NTCD) (n=54) and T-cell depleted (TCD) (n=95). Study endpoints were overall survival (OS), progression free survival (PFS), engraftment kinetics (neutrophil and platelet recovery), incidence of acute graft versus host disease (acute GVHD), chronic GVHD, nonrelapse mortality (NRM) and disease relapse. Multivariate analysis showed that higher infused CD34+ cell dose improved OS (relative risk 0.58, 95% CI 0.34-0.98, P=.04), PFS (relative risk 0.59, 95% CI 0.35-1.00, P=.05) and NRM (relative risk 0.49, 95% CI 0.24-0.99, P=.048) in the TCD group. By multivariate analysis, there was no difference in engraftment, grades II-IV acute GVHD, extensive chronic GVHD and relapse in the two groups relative to the infused cell doses. There was a trend towards improved OS (relative risk 0.54, 95% CI 0.29-1.01, P=.05) with higher CD3+ cell dose in the TCD group. Our findings suggest that higher CD34+ cell dose imparts survival benefit only to in vivo TCD peripheral blood AHCT recipients.

  6. Comparative effectiveness and tolerability of esomeprazole and omeprazole in gastro-esophageal reflux disease: A systematic review and meta-analysis.

    Science.gov (United States)

    Qi, Qian; Wang, Rugang; Liu, Lin; Zhao, Feng; Wang, Sheng

    2015-10-01

    This study aims to evaluate the effectiveness and tolerability of esomeprazole and omeprazole in patients with gastroesophageal reflux disease (GERD). Electronic searches on PubMed, EMBASE, the Cochrane Library, and ClinicalTrials.gov databases were carried out for reports up to February 28, 2015. Ten eligible studies from 8 articles were found that enrolled a total of 10,286 patients for meta-analysis. These results revealed a significant difference between esomeprazole vs. omeprazole (RR=1.06, 95% CI [1.01, 1.10], I2=72%, p=0.01) by subgroup according to dosage by random effects model, and a significant difference between esomeprazole 40 mg vs. omeprazole 20 mg (RR=1.07, 95% CI [1.004, 1.14], I2=78%, p=0.04) based on healing rate as determined by endoscopy, using a random effects model. A significant difference between esomeprazole 20 mg and omeprazole 40 mg (RR=0.68, 95% CI [0.47, 0.97], I2=not applicable, p=0.03) was also found in comparing relief of symptoms by random effects model. There were no significant differences in outcomes between other subgroups, including tolerability. Based on these results, a high dose of esomeprazole is recommended for GERD treatment and control in adults.

  7. Eight weeks of omeprazole 20 mg significantly reduces both laryngopharyngeal reflux and comorbid chronic rhinosinusitis signs and symptoms: Randomised, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Anzić, S A; Turkalj, M; Župan, A; Labor, M; Plavec, D; Baudoin, T

    2018-04-01

    Gastroesophageal reflux recommended treatment (dose and duration) with proton-pump inhibitor (PPI) compared to placebo significantly reduces the signs and symptoms of laryngopharyngeal reflux (LPR) and comorbid chronic rhinosinusitis (CRS). Double-blind randomised placebo-controlled trial. Eight weeks of treatment with omeprazole 20 mg once daily (OD). Sixty patients (28 women, aged 19-87 years) with diagnosed LPR and comorbid CRS. Significant reduction in signs and symptoms (reflux symptom index (RSI) score as subjective, and reflux finding score (RFS) as objective measure) of LPR after 8 weeks of treatment with omeprazole 20 mg OD when compared to placebo. Secondary objectives were significant reduction in signs and symptoms of comorbid CRS after 8 weeks of treatment with omeprazole 20 mg OD when compared to placebo and the association of the severity of signs and symptoms of LPR with the ones of CRS. RSI and RFS decreased significantly more in the active treatment group after 8 weeks compared to placebo (P < .001 for both). CRS and endoscopy scoring decreased both significantly more in the active group after 8 weeks compared to placebo (P < .001 for both). CRS scoring significantly correlated with RSI (R = 0.312, P = .015) but not with RFS (R = 0.199, P = .127). The results of our trial suggest that omeprazole 20 mg OD for 8 weeks was effective in reducing signs and symptoms of both LPR and CRS, although in most patients still present at the end of the trial. © 2017 John Wiley & Sons Ltd.

  8. A Comparison of the Inhibitory Effect of Omeprazole And Nifedipine ...

    African Journals Online (AJOL)

    The present study was carried out to determine the effect of the gastric acid inhibitors, nifedipine (a calcium channel blocker) and omeprazole, (a proton pump inhibitor), on histamine-stimulated and carbachol stimulated gastric acid secretion in rats. Thirty intact male Sprague-Dawley rats were used for the study. The rats ...

  9. Lack of effect of omeprazole in oral acenocoumarol anticoagulant therapy

    NARCIS (Netherlands)

    Vreeburg, E. M.; de Vlaam-Schluter, G. M.; Trienekens, P. H.; Snel, P.; Tytgat, G. N.

    1997-01-01

    Omeprazole is eliminated almost completely by hepatic metabolism within the cytochrome P-450 system and might inhibit the oxidative metabolism of other drugs. This is particularly relevant for compounds with a narrow therapeutic range, such as acenocoumarol. In this study we evaluated the effect of

  10. Improvement in health-related quality of life after therapy with omeprazole in patients with coronary artery disease and recurrent angina-like chest pain. A double-blind, placebo-controlled trial of the SF-36 survey

    Directory of Open Access Journals (Sweden)

    Kłopocka Maria

    2011-09-01

    Full Text Available Abstract Background Many patients with coronary artery disease (CAD have overlapping gastroenterological causes of recurrent chest pain, mainly due to gastroesophageal reflux (GER and aspirin-induced gastrointestinal tract damage. These symptoms can be alleviated by proton pump inhibitors (PPIs. The study addressed whether omeprazole treatment also affects general health-related quality of life (HRQL in patients with CAD. Study 48 patients with more than 50% narrowing of the coronary arteries on angiography without clinically overt gastrointestinal symptoms were studied. In a double-blind, placebo-controlled, cross-over study design, patients were randomized to take omeprazole 20 mg bid or a placebo for two weeks, and then crossed over to the other study arm. The SF-36 questionnaire was completed before treatment and again after two weeks of therapy. Results Patients treated with omeprazole in comparison to the subjects taking the placebo had significantly greater values for the SF-36 survey (which relates to both physical and mental health, as well as for bodily pain, general health perception, and physical health. In comparison to the baseline values, therapy with omeprazole led to a significant increase in the three summarized health components: total SF-36; physical and mental health; and in the following detailed health concept scores: physical functioning, limitations due to physical health problems, bodily pain and emotional well-being. Conclusions A double dose of omeprazole improved the general HRQL in patients with CAD without severe gastrointestinal symptoms more effectively than the placebo.

  11. The comparasion of combined effects of vitamin D3 and Omeprazole on prevention of menopausal

    Directory of Open Access Journals (Sweden)

    ahmad Tamjidipur

    2010-02-01

    morphometrically, and the density of L4 vertebrae was determined based on Archimedes principle . The mean of variables was compared by SPSS 12 software. To compare the mean of alkaline phosphotase, serum Ca, the density of L4 vertebrae and the resistance of femur bones against fracture, we used ANOVA and Games-Howells test, and to compare the mean of volume density of trabeculae and the number of osteoclasts, Mann- Whitney test in p<0. 05 was used. Results: After 12 weeks, ovariectomy made severe osteoporosis in the 2nd and 7th groups . In the 1st, 3rh, 4th, 6th and 8th, no osteoporosis was delected, but in the 5th group, osteoporosis was detected slightly. Conclusion: Vitamin D treatment and almost DMSO prevent osteoporosis progressing. omeprazole treatment alone can prevent osteoporosis but in combination with a suitable dose of vitamin D, it can prevent osteoporosis and its progress.

  12. Prescripción, dispensación y sustitución de recetas de omeprazol Prescription, dispensation and sustitution of prescription forms of omeprazole

    Directory of Open Access Journals (Sweden)

    M. B. Vaquero

    2003-07-01

    official Spanish denomination (OSD. In either case, the cost of the prescription is expressed in terms of the defined daily dose (DDD. Method: We reviewed 592 public health service prescriptions for omeprazole 20 mg, prescribed by 56 primary care physicians with a high prescription rate for this active principle, which were dispensed in 16 pharmacies. Results: Prescriptions dispensed according to the physician's prescription (50% of the prescriptions were cheaper than those expressed in OSD and dispensed as generic drugs by pharmacists using their own criteria (36% of the cases. In all cases of substitution of the prescribed drugs (14% of prescriptions, a generic drug was dispensed and 76% of these were more expensive than the prescribed drug. Conclusions: The results show that primary care physicians tend to take into account the cost of the drug and to choose cheaper drugs even when these are not generic. When pharmacists substitute the prescribed drug, they tend to dispense a generic drug that is more expensive.

  13. Infusion of radionuclides throughout pregnancy

    International Nuclear Information System (INIS)

    Mountford-Lister, P.G.; Lambert, B.E.; Milner, A.C.; Kang, X.Z.

    1992-01-01

    This work is part of a long-term study to examine the cancer incidence in the offspring of mice exposed to 239 Pu or 147 Pm throughout pregnancy. The need to model the human intake scenario and the possibility of a critical period during uterine development necessitates constant availability of radionuclides throughout pregnancy. Various methods (multiple daily injections, infusion by external cannula and infusion by indwelling osmotic pump) have been examined and osmotic infusion pumps chosen. These pumps result in a near-constant blood concentration for up to 21 days. Part of the study is the estimation of dose to the critical haemopoietic tissues of the pup from a knowledge of the radionuclide distribution and kinetics. At present the distribution has been followed from birth to 180 days. Activity in the suckling pups at 7 days old is around 1 percent of the infused activity, though most of this is accounted for by the contents of the stomach and gastrointestinal tract. The liver and femur account for around 0.025 percent and 0.012 percent respectively per pup. Activity increases in both liver and femur during lactation after which both concentration and activity fall with time. Long-term studies with the pups of dams exposed to a range of 239 Pu concentrations between 0-70 kBq/kg are underway. Correlation of average organ dose with tumour incidence will be determined at completion of the life-span study. (Author) 39 refs., 5 tabs., 6 figs

  14. Nizatidine and omeprazole enhance the effect of metronidazole on Helicobacter pylori in vitro

    DEFF Research Database (Denmark)

    Chen, Ming; Jensen, Bente; Zhai, Lin

    2002-01-01

    Treatment failures are common in patients infected with metronidazole-resistant Helicobacter pylori in the gastric mucosa when triple therapy including metronidazole is used. In patients with treatment failure and metronidazole-resistant H. pylori, a higher eradication rate for H. pylori was found...... after secondary treatment with bismuth/ranitidine in combination with antibiotics including metronidazole, compared with the same antibiotics combined with a standard dose of omeprazole. This agrees with our previous finding that bismuth was able to reduce the susceptibility of H. pylori...... to metronidazole. In this study, we have found that nizatidine, an H(2)-receptor antagonist, is also able to reduce the susceptibility of H. pylori to metronidazole in vitro, despite having no direct inhibitory effect on the growth of H. pylori. This agrees with earlier findings that compounds having the ability...

  15. Effect of a high-dose target-controlled naloxone infusion on pain and hyperalgesia in patients following groin hernia repair: study protocol for a randomized controlled trial

    DEFF Research Database (Denmark)

    Pereira, Manuel Pedro; Utke Werner, Mads; Berg Dahl, Joergen

    2015-01-01

    transition from supine to standing position, and evoked by pressure algometry) and the secondary outcomes (secondary hyperalgesia/allodynia, pressure pain thresholds, assessed at the surgical site and at the mirror-site in the contralateral groin, and, opioid withdrawal symptoms) will be assessed......BACKGROUND: Central sensitization is modulated by the endogenous opioid system and plays a major role in the development and maintenance of pain. Recent animal studies performed following resolution of inflammatory pain showed reinstatement of tactile hypersensitivity induced by administration...... of a mu-opioid-antagonist, suggesting latent sensitization is mediated by endogenous opioids. In a recent crossover study in healthy volunteers, following resolution of a first-degree burn, 4 out of 12 volunteers developed large secondary areas of hyperalgesia areas after a naloxone infusion, while...

  16. Preliminary clinical evaluation of continuous infusion of 5-FU and low-dose cisplatin (LFP) therapy alone and combined with radiation therapy for treatment of advanced or recurrent esophageal cancer

    International Nuclear Information System (INIS)

    Itoh, Satoshi; Morita, Sojiro; Ohnishi, Takenao; Tsuji, Akihito; Takamatsu, Masahiro; Horimi, Tadashi

    2002-01-01

    We evaluated the clinical effect of 5-FU and low-dose Cisplatin (LFP) therapy alone and LFP therapy combined with radiation therapy in patients with advanced or recurrent esophageal cancer. From March 1995 to September 2000, 11 patients with inoperable esophageal cancer, 8 patients with adjuvant chemotherapy post operation, and 14 patients with recurrent esophageal cancer were treated with LFP therapy. 5-FU (160 mg/m 2 /day) was continuously infused over 24 hours, and CDDP (3-7 mg/m 2 /day) was infused for 30 minutes. The administration schedule consisted of 5-FU for 7 consecutive days and CDDP for 5 days followed by a 2-day rest, each for four weeks. We combined radiation therapy for the patients with all lesions that could be included in the radiation field. Of 30 patients with measurable lesions the response rates of LFP therapy alone and LFP therapy combined with radiation therapy were 33% and 60%, respectively. Toxicity over grade 3 appeared in 3 of 15 patients with LFP therapy combined with radiation therapy. There was no significant difference between LFP therapy alone and LFP therapy combined with radiation therapy with regard to survival rate of inoperable and recurrent esophageal cancer. In conclusion, LFP therapy alone may be effective for esophageal cancer. (author)

  17. Evergreening by whom? A review of secondary patents for omeprazole.

    Science.gov (United States)

    Lloyd, Mike

    2013-11-01

    Evergreening, or the practice of technology developers to retain legal protection over valuable drugs beyond the normal patent term, is a well known practice by originators of successful drugs. Generic competitors also attempt similar strategies for commercial reasons. In this paper we look at secondary US and European patents in relation to the 'blockbuster' drug omeprazole (e.g., Prilosec® by AstraZeneca among other brands), with these secondary patents selected because they refer to the 'omeprazole' in either the title, abstract, Derwent Title or first claim. We find that 485 patents meet this criteria, with only 29% owned by the drugs originator (or known subsidiaries or predecessors). AstraZeneca was also the leading applicant by a number of measures, including grant ratio, number of patents filed, forward citation count, family member count and claim breadth.

  18. Effects of the Proton Pump Inhibitors Omeprazole and Pantoprazole on the Cytochrome P450-Mediated Metabolism of Venlafaxine.

    Science.gov (United States)

    Kuzin, Maxim; Schoretsanitis, Georgios; Haen, Ekkehard; Stegmann, Benedikt; Hiemke, Christoph; Gründer, Gerhard; Paulzen, Michael

    2017-09-02

    BACKGROUND AND OBJECTIVE: An increasing trend in prescribing proton pump inhibitors (PPIs) inevitably increases the risk of unwanted drug-drug interactions (DDIs). The aim of this study was to uncover pharmacokinetic interactions between two PPIs-omeprazole and pantoprazole-and venlafaxine. A therapeutic drug monitoring database contained plasma concentrations of venlafaxine and its active metabolite O-desmethylvenlafaxine. We considered three groups: a group of patients who received venlafaxine without confounding medications (non-PPI group, n = 906); a group of patients who were comedicated with omeprazole (n = 40); and a group of patients comedicated with pantoprazole (n = 40). Plasma concentrations of venlafaxine, O-desmethylvenlafaxine and active moiety (venlafaxine + O-desmethylvenlafaxine), as well as dose-adjusted plasma concentrations, were compared using non-parametrical tests. Daily doses of venlafaxine did not differ between groups (p = 0.949). The Mann-Whitney U test showed significantly higher plasma concentrations of active moiety, as well as venlafaxine and O-desmethylvenlafaxine, in both PPI groups [p = 0.023, p = 0.011, p = 0.026, +29% active moiety, +27% venlafaxine, +36% O-desmethylvenlafaxine (pantoprazole); p = 0.003, p = 0.039 and p < 0.001, +36% active moiety, +27% venlafaxine, +55% O-desmethylvenlafaxine (omeprazole)]. Significantly higher concentration-by-dose (C/D) values for venlafaxine and active moiety were detected in the pantoprazole group (p = 0.013, p = 0.006, respectively), while in the omeprazole group, C/D ratios for all three parameters-venlafaxine, O-desmethylvenlafaxine and active moiety-were significantly higher (p = 0.021, p < 0.001 and p < 0.001, respectively). Significantly higher plasma concentrations for all parameters (venlafaxine, O-desmethylvenlafaxine, active moiety) suggest clinically relevant inhibitory effects of both PPIs, most likely on the cytochrome P450 (CYP) 2C19-mediated

  19. Elimination of Helicobacter pylori under treatment with omeprazole.

    Science.gov (United States)

    Stolte, M; Bethke, B

    1990-06-01

    Biopsies from the stomachs (antrum and corpus) of 201 patients with peptic ulcers or reflux oesophagitis were retrospectively investigated for the effect of treatment with omeprazole on the elimination of Helicobacter pylori (HP) and on gastritis. Of 64 patients without gastritis two (3.1%) developed gastritis during treatment. Among 134 patients with HP gastritis undergoing treatment, 48 (35.8%) experienced no HP elimination, in 41 (30.6%) there was HP elimination from the antrum, but HP persistence in the corpus, while in 45 (33.6%) HP was eliminated from both antrum and corpus. HP elimination led to a reduction in the degree and activity of gastritis under omeprazole treatment. Only eight patients were examined after completion of treatment, and in three in whom HP had been eliminated, recolonization was found to have occurred. The disappearance of HP in Type A gastritis coupled with the fact that HP is highly sensitive to contamination with other bacteria--as observed in the laboratory--suggests that this now partially established elimination of HP under the strongly acid-inhibiting omeprazole therapy can be traced back to a bacterial overgrowth of the gastric mucosa.

  20. Preliminary investigations into a novel, long-acting, injectable, intramuscular formulation of omeprazole in the horse.

    Science.gov (United States)

    Sykes, B W; Kathawala, K; Song, Y; Garg, S; Page, S W; Underwood, C; Mills, P C

    2017-11-01

    Pilot investigations have suggested that a novel, long-acting, injectable i.m. formulation of omeprazole (LA-OMEP) can induce acid suppression for up to 7 days following a single injection. To investigate the pharmacodynamics and assess the clinical efficacy of the LA-OMEP formulation. Part A comprised a pharmacodynamic study. Part B consisted of a pilot clinical trial. Part A enrolled six adult Thoroughbred horses with percutaneous gastrotomy tubes. Intragastric pH was measured for continuous 23-h periods (08.00-07.00 h) for eight consecutive days (days 0-7). A single 2.0-g dose of a 100 mg/mL LA-OMEP formulation was administered at 08.00 h on day 1. In Part B, 26 horses with squamous or glandular gastric disease were enrolled based on routine gastroscopic evaluation. Once enrolled, horses received 2.0 g of the 100 mg/mL LA-OMEP formulation by i.m. injection on days 0 and 7. Repeat gastroscopy was performed on days 14 (23 horses) or 16 (one horse). In Part A, the percentage of time during which pH was above 4 exceeded 66% for days 1-4 in all horses and days 1-7 in four of the six horses studied. In Part B, healing was observed in all 22 (100%, 95% confidence interval [CI] 89-100%) horses with squamous disease and in nine of 12 (75%, 95% CI 47-92%) horses with glandular disease. Improvement, by at least one grade, was observed in all 22 (100%, 95% CI 89-100%) horses with squamous disease and in all 12 (100%, 95% CI 81-100%) horses with glandular disease. No worsening of lesions was observed. Lesion grade decreased over time in both the squamous (P<0.0001) and glandular (P = 0.0024) mucosa. Small sample sizes. The results of the present study compare favourably with previous reports on the pharmacodynamics of omeprazole and the clinical outcomes of trials reporting response to oral omeprazole therapy. © 2017 EVJ Ltd.

  1. Low dose of dichloroacetate infusion reduces blood lactate after submaximal exercise in horses Baixa dose de infusão de dicloroacetato reduz o lactato sanguíneo após exercício submáximo em cavalos

    Directory of Open Access Journals (Sweden)

    Guilherme C. Ferraz

    2013-01-01

    guas destreinadas. As coletas de sangue foram realizadas no período após o exercício, nos momentos de 1, 3, 5, 10, 15 e 20 min. Lactato e glicose (mM foram determinados electro-enzimaticamente utilizando um analisador automático (YSI 2300. Houve redução de 15,3% no lactato sanguíneo total médio que foi determinado a partir dos valores obtidos em todos os momentos de avaliação em ambos os testes, após o exercício. Houve diminuição na lactatemia 1, 3, 5, 10, 15 e 20 minutos após exercício para as éguas que receberam infusão de DCA, com os respectivos valores médios de 6,31±0,90 versus 5,81±0,50, 6,45±1,19 versus 5,58±1,06, 6,07±1,56 versus 5,26±1,12, 4,88±1,61 versus 3,95±1,00, 3,66±1,41 versus 2,86±0,75 e 2,75±0,51 versus 2,04±0,30. Não houve diferença nas concentrações de glicose. Por meio de análise de regressão linear, V140, V160, V180 e V200 foram determinados (velocidades em que as taxas cardíacas alcançam 140, 160, 180 e 200 bpm, respectivamente. As velocidades relacionadas com a frequência cardíaca não diferiram, indicando que não houve efeito ergogênico, mas a administração prévia de uma dose relativamente baixa de DCA em éguas reduziu a lactatemia após um ETI.

  2. Effects of target-controlled infusion of high-dose naloxone on pain and hyperalgesia in a human thermal injury model: a study protocol: A randomized, double-blind, placebo-controlled, crossover trial with an enriched design.

    Science.gov (United States)

    Springborg, Anders D; Jensen, Elisabeth K; Taylor, Bradley K; Werner, Mads U

    2016-11-01

    Mu-opioid-receptor antagonists have been extensively studied in experimental research as pharmacological tools uncovering mechanisms of pain modulation by the endogenous opioid system. In rodents, administration of high doses of mu-opioid-receptor antagonists after the resolution of an inflammatory injury has demonstrated reinstatement of nociceptive hypersensitivity indicating unmasking of latent sensitization. In a recent human study, pain hypersensitivity assessed as secondary hyperalgesia area (SHA), was reinstated 7 days after a mild thermal injury, in 4 out of 12 subjects after a naloxone infusion.The aims of the present study are first, to replicate our previous findings in a larger-sized study; second, to examine if high sensitizers (subjects presenting with large SHA after a thermal injury) develop a higher degree of hypersensitivity after naloxone challenge than low sensitizers (subjects presenting with restricted SHA after a thermal injury); and third to examine a dose-response relationship between 3 stable naloxone concentrations controlled by target-controlled infusion, and the unmasking of latent sensitization.Healthy participants (n = 80) underwent a screening day (day 0) with induction of a thermal skin injury (47°C, 420 seconds, 12.5 cm). Assessment of SHA was performed 1 and 2 hours after the injury. Using an enriched design, only participants belonging to the upper quartile of SHA (Q4, high sensitizers; n = 20) and the lower quartile of SHA (Q1, low sensitizers; n = 20) continued the study, comprising 4 consecutive days-days 1 to 4. Thermal skin injuries were repeated on day 1 and day 3, whereas day 2 and day 4 (7 days after day 1 and day 3, respectively) were target-controlled infusion days in which the subjects were randomly allocated to receive either naloxone (3.25 mg/kg, 4 mg/mL) or placebo (normal saline) intravenous. The primary outcome was SHA assessed by weighted-pin instrument (128 mN) 0, 1, 2, and 165 to 169

  3. Omeprazole impairs vascular redox biology and causes xanthine oxidoreductase-mediated endothelial dysfunction

    Directory of Open Access Journals (Sweden)

    Lucas C. Pinheiro

    2016-10-01

    Full Text Available Proton pump inhibitors (PPIs are widely used drugs that may increase the cardiovascular risk by mechanisms not entirely known. While PPIs increase asymmetric dimethylarginine (ADMA levels and inhibit nitric oxide production, it is unknown whether impaired vascular redox biology resulting of increased xanthine oxidoreductase (XOR activity mediates PPIs-induced endothelial dysfunction (ED. We examined whether increased XOR activity impairs vascular redox biology and causes ED in rats treated with omeprazole. We also examined whether omeprazole aggravates the ED found in hypertension. Treatment with omeprazole reduced endothelium-dependent aortic responses to acetylcholine without causing hypertension. However, omeprazole did not aggravate two-kidney, one-clip (2K1C hypertension, nor hypertension-induced ED. Omeprazole and 2K1C increased vascular oxidative stress as assessed with dihydroethidium (DHE, which reacts with superoxide, and by the lucigenin chemiluminescence assay. The selective XOR inhibitor febuxostat blunted both effects induced by omeprazole. Treatment with omeprazole increased plasma ADMA concentrations, XOR activity and systemic markers of oxidative stress. Incubation of aortic rings with ADMA increased XOR activity, DHE fluorescence and lucigenin chemiluminescence signals, and febuxostat blunted these effects. Providing functional evidence that omeprazole causes ED by XOR-mediated mechanisms, we found that febuxostat blunted the ED caused by omeprazole treatment. This study shows that treatment with omeprazole impairs the vascular redox biology by XOR-mediated mechanisms leading to ED. While omeprazole did not further impair hypertension-induced ED, further studies in less severe animal models are warranted. Our findings may have major relevance, particularly to patients with cardiovascular diseases taking PPIs.

  4. Effect of esomeprazole with/without acetylsalicylic acid, omeprazole and lansoprazole on pharmacokinetics and pharmacodynamics of clopidogrel in healthy volunteers.

    Science.gov (United States)

    Andersson, Tommy; Nagy, Peter; Niazi, Mohammad; Nylander, Sven; Galbraith, Hal; Ranjan, Santosh; Wallentin, Lars

    2014-06-01

    The effect of proton pump inhibitors (PPIs) on the pharmacokinetics and pharmacodynamics of clopidogrel was assessed in two healthy volunteer crossover studies. Study 1: subjects received clopidogrel alone (300-mg loading dose, then 75 mg/day for 28 days) and two of three PPIs (omeprazole 80 mg, esomeprazole 40 mg or lansoprazole 60 mg) plus clopidogrel for 29 days in three treatment periods (randomized treatment sequence assignment). Study 2: subjects received clopidogrel alone (75 mg/day for 9 days) and clopidogrel alone for 4 days followed by clopidogrel plus fixed-combination esomeprazole 20 mg/low-dose acetylsalicylic acid (ASA) 81 mg for 5 days in two treatment periods (randomized treatment sequence assignment). Pharmacokinetic effects were estimated by measuring active metabolite of clopidogrel, and pharmacodynamic effects by inhibition of adenosine diphosphate (ADP)-induced platelet aggregation. There was a relative decrease of up to 50 % in exposure to the active metabolite of clopidogrel with the different PPIs (study 1), and close to 40 % with esomeprazole/low-dose ASA (study 2), compared with clopidogrel alone. There was an absolute decrease of up to 17 % in inhibition of ADP-induced platelet aggregation with co-administration of different PPIs, compared with clopidogrel alone; however, no differences in platelet inhibition were observed during co-administration with the esomeprazole/low-dose ASA fixed-dose combination. Omeprazole, esomeprazole and lansoprazole decreased systemic exposure to the active metabolite of clopidogrel in healthy volunteers, leading to modest decreases in its antiplatelet effect. However, no apparent differences in platelet inhibition were observed when esomeprazole was co-administered with low-dose ASA as a fixed-dose combination.

  5. Sevoflurano e desflurano sobre o ritmo cardíaco de cães tratados com infusão contínua de doses crescentes de adrenalina

    Directory of Open Access Journals (Sweden)

    Nunes Newton

    2004-01-01

    Full Text Available Os anestésicos inalatórios sensibilizam o miocárdio ou seu sistema de condução à ação das catecolaminas endógenas e/ou exógenas, predispondo o animal às arritmias cardíacas. Dentre os anestésicos voláteis, o sevoflurano e o desflurano são fármacos relativamente recentes e, embora sejam dotados de características relacionadas a não sensibilização do miocárdio às catecolaminas, desconhecem-se estudos que comparem suas eventuais propriedades antiarritmogênicas. Com o objetivo de estudar, comparativamente, o comportamento do ritmo cardíaco e observar eventuais bloqueios atrioventriculares em cães anestesiados pelo sevoflurano e desflurano e submetidos à infusão contínua de adrenalina, foram utilizados 20 animais adultos, os quais foram separados em dois grupos de igual número (G1 e G2. Aos cães do G1, foi administrado propofol, na dose média de 10mmg.kg-1; em seguida os animais receberam sevoflurano, a 1,5CAM. Decorridos 30 minutos do início da administração do anestésico volátil, iniciou-se a infusão de adrenalina na dose de 1mmg.kg-1.min-1. A cada 10 minutos, a dose da catecolamina foi acrescida em uma unidade, cessando-se a administração em 6mmg.kg-1.min-1. Para o G2, empregou-se a mesma metodologia, substituindo-se o sevoflurano pelo desflurano, administrado a 1,5CAM. A cada dose de adrenalina, foi feita contagem de batimentos ventriculares ectópicos, bem como a observação de bloqueios atrioventriculares. Os achados foram tratados pelos métodos estatísticos de Análise de Perfil e Kruskall-Wallis. Os resultados permitiram concluir que o desflurano minimiza de maneira mais eficiente a arritmia induzida pela adrenalina, além de reduzir a incidência de bloqueios atrioventriculares.

  6. Variáveis fisiológicas em cães submetidos à infusão contínua de diferentes doses de propofol Physiologic parameters in dogs anesthetized with different rates of continuous infusion of propofol

    Directory of Open Access Journals (Sweden)

    Patrícia Cristina Ferro

    2005-10-01

    Full Text Available A fim de determinar possíveis alterações nos principais parâmetros fisiológicos determinados pela infusão contínua de propofol, em diferentes doses, foram utilizados 24 cães adultos distribuídos aleatoriamente em 3 grupos (P2, P4 e P8. Os animais foram induzidos à anestesia pela administração intravenosa de propofol (10mg/kg e, ato contínuo, os cães receberam o anestésico, em infusão contínua nas doses de 0,2mg/kg/min (P2, 0,4mg/kg/min (P4 e 0,8mg/kg/min (P8. As mensurações dos valores das variáveis cardiorrespiratórias [freqüência cardíaca (FC; pressões arteriais sistólica, diastólica e média (PAS, PAD e PAM, respectivamente; eletrocardiografia e freqüência respiratória (f] e temperatura retal (T foram realizadas antes da aplicação do fármaco (M0 e após 10, 20, 30, 40 e 50 minutos do início da infusão contínua. Os dados numéricos das variáveis estudadas foram submetidos à Análise de Variância (ANOVA seguida pelo Teste F (PThe aim of this article was to establish the correlation between different rates of continuous infusion of propofol and the alterations that might occur with the physiologic parameters most commonly measured by the anesthesiologists. Twenty four adult dogs were randomly divided into 3 groups (P2, P4, P8. All the animals were induced with propofol (10mg/kg, followed immediately by the continuous infusion of the agent: 0.2mg/kg/min (P2, 0.4mg/kg/min (P4 and 0.8mg/kg/min (P8. The heart rate (HR, systolic, diastolic and mean arterial pressures (SAP, DAP and MAP, electrocardiography (ECG, respiratory rate (RR, and body temperature (T were measured before any drug administration (M0 and 10, 20, 30, 40 and 50 minutes after the start of the continuous infusion of propofol. The numerical data were submitted to Profile of Variance followed by F Test (P<0.05. The HR showed differences among groups at M20 (P2: 91 ± 14,92; P4: 113 ± 17,18; P8: 120 ± 14,84, M30 (P2: 89 ± 13,79; P4: 110 ± 14

  7. Effects of long-term administration of omeprazole on bone mineral density and the mechanical properties of the bone

    Directory of Open Access Journals (Sweden)

    Gabriela Rezende Yanagihara

    2015-04-01

    Full Text Available OBJECTIVES: Epidemiological studies have shown a relationship between long-term use of proton pump inhibitors and bone metabolism. However, this relationship has not yet become established. The aim of the present study was to analyze the mechanical properties and bone mineral density (BMD of rats that were subjected to long-term omeprazole use.METHODS: Fifty Wistar rats weighing between 200 and 240 g were divided equally into five groups: OMP300 (omeprazole intake at a dose of 300 µmoL/kg/day; OMP200 (200 µmoL/kg/day; OMP40 (40 µmoL/kg/day; OMP10 (10 µmoL/kg/day; and Cont (control group; intake of dilution vehicle. The solutions were administered for 90 consecutive days. After the rats had been sacrificed, their BMD, the mechanical properties of the dissected femurs and their serum Ca++ levels were analyzed.RESULTS: The BMD of the OMP300 group was lower than that of the controls (p = 0.006. There was no difference on comparing the OMP200, OMP40 and OMP10 groups with the controls. The maximum strength and rigidity of the femur did not differ in the experimental groups in comparison with the controls. The OMP300 group had a statistically lower serum Ca++ concentration than that of the controls (p = 0.049, but the other groups did not show any difference in relation to the controls.CONCLUSION: Daily intake of 300 µmoL/kg/day of omeprazole decreased the BMD of the femur, but without changes to the rigidity and strength of the femur in adult rats.

  8. Intravenous iron isomaltoside 1000 administered by high single-dose infusions or standard medical care for the treatment of fatigue in women after postpartum haemorrhage

    DEFF Research Database (Denmark)

    Holm, Charlotte; Thomsen, Lars Lykke; Norgaard, Astrid

    2015-01-01

    randomised controlled studies have compared the clinical efficacy and safety of standard medical care with intravenous administration of iron supplementation after postpartum haemorrhage.The primary objective of this study is to compare the efficacy of an intravenous high single-dose of iron isomaltoside...... medical care. Healthy parturients with a singleton pregnancy will be included within 48 hours after delivery.Participants will complete structured questionnaires that focus on several dimensions of fatigue and mental health (Multidimensional Fatigue Inventory, Edinburgh Postnatal Depression Scale...... Inventory. The primary objective will be considered to have been met if an intravenous high single dose of iron isomaltoside 1000 is shown to be superior to standard medical care in women after postpartum haemorrhage regarding physical fatigue.For claiming superiority, we set the minimal clinically relevant...

  9. A randomized trial of the effect of low dose epinephrine infusion in addition to tranexamic acid on blood loss during total hip arthroplasty

    DEFF Research Database (Denmark)

    Jans, Ø; Grevstad, Jens Ulrik; Mandøe, H

    2016-01-01

    BACKGROUND: Total hip arthroplasty (THA) is associated with both intraoperative and postoperative blood loss resulting in anaemia and, in some patients, transfusion of red blood cells. Epinephrine enhances coagulation by several mechanisms. We evaluated the effect of intraoperative low dose...... randomized, 6 were excluded, leaving 100 subjects for analyses. Mean duration of surgery was 58 (21) min. Intraoperative blood loss was 343 (95% CI 300-386) ml in the epinephrine group compared with 385 (353-434) ml in the placebo group, P = 0.228. 24 h blood loss was 902 (800-1004) ml in the epinephrine...... on low dose epinephrine in patients at high risk of significant bleeding are warranted. CLINICAL TRIAL REGISTRATION: NCT 01708642....

  10. Enhanced pharmacokinetics of omeprazole when formulated as gastroretentive microspheres along with piperine

    Directory of Open Access Journals (Sweden)

    Bindu Madhavi Boddupalli

    2014-02-01

    Full Text Available Objective: To investigate the formulation of gastroretentive microspheres of omeprazole along with piperine and estimate the pharmacokinetic parameters in comparison with omeprazole alone. Methods: In our present investigation, gastroretentive microspheres of omeprazole were prepared with the inclusion of piperine. Pharmacokinetic parameters like Cmax, Tmax and area under curve were estimated by administering the prepared microspheres to rabbits and the results were compared with omeprazole alone. Results: There was a significant increase in area under curve from 3.441依1.093 mg·h/mL to 14.422 依0.708 mg·h/mL along with an increase in Cmax. Conclusions: This clearly shows the increased absorption and decreased metabolism of omeprazole when administered along with piperine as gastroretentive microspheres.

  11. Iron concentration in breast milk normalised within one week of a single high-dose infusion of iron isomaltoside in randomised controlled trial

    DEFF Research Database (Denmark)

    Holm, Charlotte; Thomsen, Lars Lykke; Nørgaard, Astrid

    2017-01-01

    at a mean daily dose of 70.5mg. We included 65 women with sufficient breast milk three days after inclusion - 30 from the intravenous iron group and 35 from the oral iron group - and collected breast milk and maternal blood samples three days and one week after allocation. RESULTS: The mean (± standard...... deviation) iron concentration in breast milk in the intravenous and oral groups were 0.72 ± 0.27 mg/L and 0.40 ± 0.18 mg/L at three days (p

  12. The Effect of Food or Omeprazole on the Pharmacokinetics of Osimertinib in Patients With Non-Small-Cell Lung Cancer and in Healthy Volunteers.

    Science.gov (United States)

    Vishwanathan, Karthick; Dickinson, Paul A; Bui, Khanh; Cassier, Philippe A; Greystoke, Alastair; Lisbon, Eleanor; Moreno, Victor; So, Karen; Thomas, Karen; Weilert, Doris; Yap, Timothy A; Plummer, Ruth

    2018-04-01

    Two phase 1, open-label studies assessed the impact of food or gastric pH modification (omeprazole) on the exposure and safety/tolerability of osimertinib and its metabolites. The food effect study was an open-label, 2-period crossover study in patients with advanced non-small-cell lung cancer, randomized into 2 treatment sequences: single-dose osimertinib 80 mg in a fed then fasted state or fasted then fed. The gastric pH study was an open-label, 2-period fixed sequence study assessing the effect of omeprazole on osimertinib exposure in healthy male volunteers. In period 1, volunteers received omeprazole 40 mg (days 1-4), then omeprazole 40 mg plus osimertinib 80 mg (day 5). In period 2, volunteers received osimertinib 80 mg alone (single dose). Blood samples were collected at prespecified time points for pharmacokinetic analyses. Safety/tolerability was also assessed. In the food effect study 38 patients were randomized to fed/fasted (n = 18) or fasted/fed (n = 20) sequences with all patients completing treatment. Coadministration with food did not affect osimertinib exposure (geometric least-squares mean ratios [90% confidence intervals]: 106.05% [94.82%, 118.60%] [area under the plasma concentration time curve from zero to 72 hours] and 92.75% [81.40%, 105.68%] [maximum plasma concentration]). In the gastric pH study (n = 68 received treatment, n = 47 completed the study), coadministration with omeprazole did not affect osimertinib exposure (geometric least-squares mean ratios 106.66% [100.26%, 113.46%] [area under the concentration-time curve], 101.65% [94.65%, 109.16%] [peak concentration]). Osimertinib was well tolerated in both studies. Osimertinib may be administered without regard to food. Dose restriction is not required in patients whose gastric pH may be altered by concomitant agents or medical conditions. ClinicalTrials.gov: NCT02224053, NCT02163733. © 2017, The American College of Clinical Pharmacology.

  13. Delayed-release oral suspension of omeprazole for the treatment of erosive esophagitis and gastroesophageal reflux disease in pediatric patients: a review

    Directory of Open Access Journals (Sweden)

    Alice Monzani

    2010-03-01

    Full Text Available Alice Monzani, Giuseppina Oderda1Department of Pediatrics, Università del Piemonte Orientale, Novara, ItalyAbstract: Omeprazole is a proton-pump inhibitor indicated for gastroesophageal reflux disease and erosive esophagitis treatment in children. The aim of this review was to evaluate the efficacy of delayed-release oral suspension of omeprazole in childhood esophagitis, in terms of symptom relief, reduction in reflux index and/or intragastric acidity, and endoscopic and/or histological healing. We systematically searched PubMed, Cochrane and EMBASE (1990 to 2009 and identified 59 potentially relevant articles, but only 12 articles were suitable to be included in our analysis. All the studies evaluated symptom relief and reported a median relief rate of 80.4% (range 35%–100%. Five studies reported a significant reduction of the esophageal reflux index within normal limits (<7% in all children, and 4 studies a significant reduction of intra-gastric acidity. The endoscopic healing rate, reported by 9 studies, was 84% after 8-week treatment and 95% after 12-week treatment, the latter being significantly higher than the histological healing rate (49%. In conclusion, omeprazole given at a dose ranging from 0.3 to 3.5 mg/kg once daily (median 1 mg/kg once daily for at least 12 weeks is highly effective in childhood esophagitis.Keywords: proton pump inhibitors, children, ranitidine, H2-blockers

  14. Tolerance to continuous intrathecal baclofen infusion can be reversed by pulsatile bolus infusion

    NARCIS (Netherlands)

    Heetla, H. W.; Staal, M. J.; van Laar, T.

    Study design: Pilot study. Objective: To study the effect of pulsatile bolus infusion of intrathecal baclofen (ITB) on daily ITB dose, in patients showing dose increases, probably due to tolerance. Setting: Department of neurology and neurosurgery, University Medical Center Groningen, the

  15. Omeprazole use at University Hospital in Porto Alegre-RS (Brazil / Uso de omeprazol en el hospital universitario de Porto Alegre-RS (Brasil / Uso de omeprazol em hospital universitário de Porto Alegre-RS (Brasil

    Directory of Open Access Journals (Sweden)

    Morrone FB

    2004-12-01

    Full Text Available Intestinal bleeding are important cause of hospital admissions and death, being relevant in critically weak patients and those with arthritis and osteoarthritis using NSAIDs. Omepazole is the first choice drug for prophylaxis of stress ulcer and NSAID complications prevention, because it prevent not only duodenal but also gastric ulcer and eradication of H pylori used with antibiotics. The aim of this study was to determine frequency of use, indications and characteristics of population using omeprazole. A qualitative and quantitative drug utilization study was done. In-hospital adults at a University Hospital constituted study population. From 91 patients studied, the majority suffered from cancer (24.2%. Average length of stay and omeprazole use time was 20 and 12 days, respectively. Abdominal surgery team was the higher omeprazole prescriber, and main indication was post-surgery. Although most of omeprazole uses was acceptable, those could be better evaluated. T could be useful implementing a pharmaceutical care program and creating a omeprazole use guideline with the objective of prescribing it in a more rationale and adequate way for each patient.

  16. A Phase 1 Pharmacokinetic Study of Cysteamine Bitartrate Delayed-Release Capsules Following Oral Administration with Orange Juice, Water, or Omeprazole in Cystinosis.

    Science.gov (United States)

    Armas, Danielle; Holt, Robert J; Confer, Nils F; Checani, Gregg C; Obaidi, Mohammad; Xie, Yuli; Brannagan, Meg

    2018-02-01

    Cystinosis is a rare, metabolic, autosomal recessive, genetic lysosomal storage disorder characterized by an accumulation of cystine in various organs and tissues. Cysteamine bitartrate (CB) is a cystine-depleting aminothiol agent approved in the United States and Europe in immediate-release and delayed-release (DR) formulations for the treatment of nephropathic cystinosis in children and adults. It is recommended that CBDR be administered with fruit juice (except grapefruit juice) for maximum absorption. Omeprazole is a proton pump inhibitor that inhibits gastric acid secretion and, theoretically, may cause the premature release of cysteamine by increasing intragastric pH, thereby affecting the PK of CBDR. This open-label, three-period, randomized study in healthy adult subjects was designed primarily to compare the pharmacokinetics of CBDR capsules after a single oral dose administered with orange juice, water, or multiple oral doses of omeprazole with water at steady state. A total of 32 subjects were randomly assigned to receive study agents in one of two treatment sequences. All subjects completed the study and baseline characteristics of the overall population and the two treatment sequence populations were similar. Peak mean plasma cysteamine concentrations following co-administration of CBDR capsules with orange juice (1892 ng/mL) were higher compared with co-administration with water (1663 ng/mL) or omeprazole 20 mg and water (1712 ng/mL). Mean time to peak plasma concentration was shorter with omeprazole co-administration (2.5 h) compared with orange juice (3.5 h) or water (3.0 h). Statistical comparisons between treatment groups indicated that exposure as assessed by AUC 0-t , AUC 0-∞ , and C max were all within the 80-125% bioequivalence ranges for all comparisons. All treatments were generally well tolerated. Overall, the pharmacokinetics of cysteamine bitartrate DR capsules are not significantly impacted by co-administration with orange juice

  17. The Tolerability and Efficacy of Rapid Infliximab Infusions in Patients with Inflammatory Bowel Disease.

    Science.gov (United States)

    Qazi, Taha; Shah, Bhavesh; El-Dib, Mohammed; Farraye, Francis A

    2016-02-01

    Few studies have assessed the loss of efficacy or patient and caregiver satisfaction with rapid infliximab infusions. The aim of this study is to assess the tolerability, loss of efficacy and to describe the impact on resource utilization and patient satisfaction in rapid infliximab infusions. Subjects with inflammatory bowel disease receiving rapid infliximab infusions were included in the study. Subjects received maintenance infusions from June 2011 to June 2013. Incidence of adverse reactions and the total number of rapid infliximab infusions were recorded. Efficacy was compared to published studies evaluating the long-term efficacy of infliximab infusions. Patient satisfaction was addressed through a survey following the implementation of the rapid infusion protocol. Seventy-five subjects with IBD were included in the study. Five hundred and twenty-two rapid infliximab infusions were provided to patients. There were no acute or delayed infusion reactions. Ten subjects (13 %) required either a dose escalation or interval adjustment between infliximab infusions. A majority of patients reported increased satisfaction with 1-h infliximab infusions, and 97 % of surveyed patients opted to continue rapid infusions. The rapid infliximab infusion protocol increased infusion unit efficiency by increasing capacity by 15 %. Cost savings in the elimination of nursing time translated to approximately $108,150 savings at our institution. Rapid infliximab infusions do not appear to increase the risk of loss of response compared to historical studies of long-term infliximab efficiency. A rapid infliximab infusion protocol improved efficiency in our infusion unit and increased patient and nursing satisfaction.

  18. 21 CFR 526.88 - Amoxicillin trihydrate for intramammary infusion.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Amoxicillin trihydrate for intramammary infusion... Amoxicillin trihydrate for intramammary infusion. (a) Specifications. Each single dose syringe contains amoxicillin trihydrate equivalent to 62.5 milligrams of amoxicillin. (b) Sponsor. See No. 000061 in § 510.600...

  19. Continuous-infusion adriamycin

    International Nuclear Information System (INIS)

    Benjamin, R.S.; Chawla, S.P.; Ewer, M.S.; Hortobagyi, G.N.

    1986-01-01

    This chapter discusses the diminished cardiotoxicity as well as diminished nausea and vomiting with continuous infusions of adriamycin to patients undergoing radiation therapy, particularly with infusions of 48 hours or longer, and best with 96-hour infusions, the longest duration that has been studied systematically. In breast cancer, data show that more adriamycin is better, but only for a selected subgroup of patients: those with complete remission. The diminished cardiotoxicity makes the use of adriamycin more attractive in the adjuvant situation, where increased safety will decrease the chances of long-term complications and make retreatment easy for cured patients who develop second malignancies

  20. Omeprazole Minimally Alters the Fecal Microbial Community in Six Cats: A Pilot Study

    Directory of Open Access Journals (Sweden)

    Sarah M. Schmid

    2018-04-01

    Full Text Available Although they have historically been thought of as safe medications, proton pump inhibitors such as omeprazole have been associated with an increased risk of enteric, particularly Clostridium difficile, infections in people. In cats, omeprazole is often the first choice acid suppressant prescribed for the treatment of upper gastrointestinal (GI ulceration and bleeding. Despite this, no studies to date have explored the effect of omeprazole on the feline fecal microbiome and metabolome. Therefore, the purpose of this pilot study was to evaluate the effect of prolonged omeprazole administration on the fecal microbiome and metabolome in healthy cats to identify targets for analysis in a larger subset of cats with GI disease. A within-subjects, before and after, pilot study was performed whereby six healthy adult cats received 60 days of placebo (250 mg lactose PO q 12 h followed by 5 mg (0.83–1.6 mg/kg PO q 12 h omeprazole. On days 0, 30, and 60 of placebo and omeprazole therapy, the fecal microbiome and metabolome were characterized utilizing 16S ribosomal RNA sequencing by Illumina and untargeted mass spectrometry-based methods, respectively. Omeprazole administration resulted in no significant changes in the global microbiome structure or richness. However, transient changes were noted in select bacterial groups with omeprazole administration resulting in an increased sequence percentage of Streptococcus, Lactobacillus, Clostridium, and Faecalibacterium spp. and a decreased sequence percentage of Bifidobacterium spp. Significance was lost for all of these bacterial groups after adjustment for multiple comparisons. The fecal concentration of O-acetylserine and aminomalonate decreased with omeprazole therapy, but significance was lost after adjustment for multiple comparisons. The results of this pilot study conclude that omeprazole has a mild and transient impact on the fecal microbiome and metabolome when orally administered to

  1. A double-blind placebo-controlled trial of omeprazole on urinary pH in healthy subjects

    DEFF Research Database (Denmark)

    Osther, P J; Rasmussen, L; Pedersen, S A

    1992-01-01

    male subjects took placebo and omeprazole, 40 mg o.m., for 10 days in a double-blind placebo-controlled trial. Morning fasting urinary pH was measured on day 10 of each treatment course using a pH meter. No effect of omeprazole on urinary pH could be demonstrated. It is thus unlikely......Urinary pH is related to urinary calculus formation as well as urinary infection. Omeprazole is an effective inhibitor of gastric acid secretion through inhibition of the parietal cell H+K+ATPase. In this study we have evaluated a possible effect of omeprazole on urine acidification. Ten healthy...... that it is necessary to take omeprazole treatment into consideration in stone screening. As omeprazole did not affect urinary pH, no urological side effects related to changes in urinary pH can be expected....

  2. A double-blind placebo-controlled trial of omeprazole on urinary pH in healthy subjects

    DEFF Research Database (Denmark)

    Osther, P J; Rasmussen, L; Pedersen, S A

    1992-01-01

    Urinary pH is related to urinary calculus formation as well as urinary infection. Omeprazole is an effective inhibitor of gastric acid secretion through inhibition of the parietal cell H+K+ATPase. In this study we have evaluated a possible effect of omeprazole on urine acidification. Ten healthy...... male subjects took placebo and omeprazole, 40 mg o.m., for 10 days in a double-blind placebo-controlled trial. Morning fasting urinary pH was measured on day 10 of each treatment course using a pH meter. No effect of omeprazole on urinary pH could be demonstrated. It is thus unlikely...... that it is necessary to take omeprazole treatment into consideration in stone screening. As omeprazole did not affect urinary pH, no urological side effects related to changes in urinary pH can be expected....

  3. Omeprazole Inhibits Acetylsalicylic Acid-Modified Histamine Stimulation of Acid Secretion in Rabbit Gastric Glands

    Directory of Open Access Journals (Sweden)

    Daniel T Brosseuk

    1994-01-01

    Full Text Available The effects of misoprostol and omeprazole on basal-, histamine- and acetylsalicylic acid (ASA-induced gastric acid secretion by isolated rabbit gastric glands were studied. The authors found that ASA at a concentration of 2.4×10-3 M significantly inhibited acid secretion in the isolated gastric glands to 65% of basal levels, and that ASA at a concentration of 2.4×l0-2 M significantly inhibited the histamine stimulation of acid secretion to 78% of maximal. Misoprostol inhibited acid secretion to 76% of basal acid secretion, while omeprazole inhibited secretion to 58% of basal values. Misoprostol inhibited the ASA-modified histamine stimulation to 82% of maximal stimulation. In contrast, omeprazole was able to inhibit the ASA-modified histamine stimulation to 48% of maximal. This omeprazole inhibition of secretagogue-induced acid production reduced acid secretion to levels below basal secretion, indicating that neither histamine nor ASA (at the concentrations used, alone or in combination, had any stimulatory effect in the presence of omeprazole. Misoprostol is the recommended drug of choice for prevention and treatment of nonsteroidal anti-inflammatory drug (NSAID-induced gastrointestinal mucosal injury. In vitro results suggest that omeprazole appears to treat this condition more effectively if gastric acid secretion is a necessary prerequisite for NSAID-induced mucosal injury.

  4. Omeprazole Alleviates Aristolochia manshuriensis Kom-Induced Acute Nephrotoxicity.

    Directory of Open Access Journals (Sweden)

    Lianmei Wang

    Full Text Available Aristolochia manshuriensis Kom (AMK is a member of the Aristolochiaceae family and is a well-known cause of aristolochic acid (AA nephropathy. In this study, we investigated the potential of omeprazole (OM to alleviate AMK-induced nephrotoxicity. We found that OM reduced mouse mortality caused by AMK and attenuated AMK-induced acute nephrotoxicity in rats. OM enhanced hepatic Cyp 1a1/2 and renal Cyp 1a1 expression in rats, as well as CYP 1A1 expression in human renal tubular epithelial cells (HKCs. HKCs with ectopic CYP 1A1 expression were more tolerant to AA than the control cells. Therefore, OM may alleviate AMK-mediated acute nephrotoxicity through induction of CYP 1A1. We suggest that the coadministration of OM might be beneficial for reducing of AA-induced nephrotoxicity.

  5. Assessment of implantable infusion pumps for continuous infusion of human insulin in rats: potential for group housing

    DEFF Research Database (Denmark)

    Jensen, Vivi Flou Hjorth; Molck, Anne-Marie; Martensson, Martin

    2017-01-01

    compound in these studies, and a comparator model of persistent exposure by HI infusion from external pumps has recently been developed to support toxicological evaluation of long-acting insulin analogues. However, this model requires single housing of the animals. Developing an insulin-infusion model...... which allows group housing would therefore greatly improve animal welfare. The aim of the present study was to investigate the suitability of implantable infusion pumps for HI infusion in group-housed rats. Group housing of rats implanted with a battery-driven pump proved to be possible. Intravenous...... infusion of HI lowered blood glucose levels persistently for two weeks, providing a comparator model for use in two-week repeated-dose toxicity studies with new long-acting insulin analogues, which allows group housing, and thereby increasing animal welfare compared with an external infusion model....

  6. Endothelial Cell Toxicity of Vancomycin Infusion Combined with Other Antibiotics

    Science.gov (United States)

    Drouet, Maryline; Chai, Feng; Barthélémy, Christine; Lebuffe, Gilles; Debaene, Bertrand; Odou, Pascal

    2015-01-01

    French guidelines recommend central intravenous (i.v.) infusion for high concentrations of vancomycin, but peripheral intravenous (p.i.v.) infusion is often preferred in intensive care units. Vancomycin infusion has been implicated in cases of phlebitis, with endothelial toxicity depending on the drug concentration and the duration of the infusion. Vancomycin is frequently infused in combination with other i.v. antibiotics through the same administrative Y site, but the local toxicity of such combinations has been poorly evaluated. Such an assessment could improve vancomycin infusion procedures in hospitals. Human umbilical vein endothelial cells (HUVEC) were challenged with clinical doses of vancomycin over 24 h with or without other i.v. antibiotics. Cell death was measured with the alamarBlue test. We observed an excess cellular death rate without any synergistic effect but dependent on the numbers of combined infusions when vancomycin and erythromycin or gentamicin were infused through the same Y site. Incompatibility between vancomycin and piperacillin-tazobactam was not observed in our study, and rinsing the cells between the two antibiotic infusions did not reduce endothelial toxicity. No endothelial toxicity of imipenem-cilastatin was observed when combined with vancomycin. p.i.v. vancomycin infusion in combination with other medications requires new recommendations to prevent phlebitis, including limiting coinfusion on the same line, reducing the infusion rate, and choosing an intermittent infusion method. Further studies need to be carried out to explore other drug combinations in long-term vancomycin p.i.v. therapy so as to gain insight into the mechanisms of drug incompatibility under multidrug infusion conditions. PMID:26055373

  7. Continuous radioisotope infusion

    International Nuclear Information System (INIS)

    Soederborg, B.; Asaba, H.; Gunnarsson, B.; Jekell, K.; Kiibus, A.; Sandqvist, S.

    1978-01-01

    Continuous infusion of a radioactive marker was used instead of a conventional bolus injection to improve haemodynamic studies. Tc-99m was infused into the blood circulation at a constant rate for 100-300 seconds and the activity in the target structure was measured by a gamma camera with a computer system or by a single detector. The concentration of the marker increased linearly at the same rate throughout the circulating system. Due to variations in transport time from infusion site to different parts of the system the rise of activity occurred at different times. A theory for the calculations was presented and consequently confirmed in a model study. Blood flow patterns in artificial kidneys and alterations in renal blood flow induced by angiotensin were studied. The results are presented as time-function curves or as computer images. This technique can be used to evaluate distributions and alterations of flow in separate parts of a complex circulating system. (author)

  8. Comparison of proton pump inhibitor and histamine-2 receptor antagonist in the prevention of recurrent peptic ulcers/erosions in long-term low-dose aspirin users: a retrospective cohort study.

    Science.gov (United States)

    Chen, Wen-Chi; Li, Yun-Da; Chiang, Po-Hung; Tsay, Feng-Woei; Chan, Hoi-Hung; Tsai, Wei-Lun; Tsai, Tzung-Jiun; Wang, E-Ming; Cheng, Jin-Shiung; Lai, Kwok-Hung

    2014-01-01

    Proton pump inhibitor and histamine-2 receptor antagonist can prevent aspirin-related ulcers/erosions but few studies compare the efficacy of these two agents. Aims. We evaluated the efficacy of omeprazole and famotidine in preventing recurrent ulcers/erosions in low-dose aspirin users. The 24-week clinical outcomes of the patients using low-dose aspirin for cardiovascular protection with a history of ulcers/erosions and cotherapy of omeprazole or famotidine were retrospectively reviewed. The incidence of gastrointestinal symptoms, recurrent ulcers/erosions, erosive esophagitis, gastrointestinal bleeding, and thromboembolic events was analyzed. A total of 104 patients (famotidine group, 49 patients; omeprazole group, 55 patients) were evaluated. Famotidine group had more gastrointestinal symptoms episodes than omeprazole group (46.9% versus 23.6%, P=0.01). Fifteen famotidine group patients and 5 omeprazole group patients had recurrent ulcers/erosions (30.6% versus 9.1%, P=0.005). Lanza scale was significantly lower in omeprazole group than in famotidine group (1.2±0.7 versus 1.7±1.1, P=0.008). Only 1 famotidine group patient had ulcer bleeding. The incidences of erosive esophagitis and thromboembolic events were comparable between both groups. Omeprazole was superior to famotidine with less gastrointestinal symptoms and recurrent ulcers/erosions in patients using 24-week low-dose aspirin. The risk of erosive esophagitis, gastrointestinal bleeding, and thromboembolic events was similar between both groups.

  9. Relevancia clínica de la interacción clopidogrel y omeprazol: revisión sistemática

    Directory of Open Access Journals (Sweden)

    Héctor Holguín, QF

    2012-01-01

    Conclusiones: la evidencia de la relevancia clínica de la interacción clopidogrel y omeprazol no es concluyente. Se recomienda seguir las indicaciones de las agencias regulatorias y, en algunos casos, sustituir omeprazol por pantoprazol.

  10. Using miniature osmotic infusion pumps to maintain tritiated thymidine exposure to cells in culture

    International Nuclear Information System (INIS)

    Neely, J.E.; Hake, D.A.

    1982-01-01

    To provide a constant level of tracer doses of tritiated thymidine to cultured cells during continuous infusion, miniature osmotic infusion pumps were used to provide replacement thymidine. By determining the loss of isotope from the media during nonreplacement, the rate of constant infusion replacement to maintain thymidine levels was calculated. The replacement rates were similar for the three cell lines examined and allowed a standard osmotic pump infusion

  11. A comparison of oral omeprazole and intravenous cimetidine in reducing complications of duodenal peptic ulcer

    Directory of Open Access Journals (Sweden)

    Khaleghian Farzaneh

    2006-01-01

    Full Text Available Abstract Background Gastrointestinal bleeding is a common problem and its most common etiology is peptic ulcer disease. Ulcer rebleeding is considered a perilous complication for patients. To reduce the rate of rebleeding and to fasten the improvement of patients' general conditions, most emergency departments in Iran use H2-blockers before endoscopic procedures (i.e. intravenous omeprazole is not available in Iran. The aim of this study was to compare therapeutic effects of oral omeprazole and intravenous cimetidine on reducing rebleeding rates, duration of hospitalization, and the need for blood transfusion in duodenal ulcer patients. Methods In this clinical trial, 80 patients with upper gastrointestinal bleeding due to duodenal peptic ulcer and endoscopic evidence of rebleeding referring to emergency departments of Imam and Sina hospitals in Tabriz, Iran were randomly assigned to two equal groups; one was treated with intravenous cimetidine 800 mg per day and the other, with 40 mg oral omeprazole per day. Results No statistically significant difference was found between cimetidine and omeprazole groups in regards to sex, age, alcohol consumption, cigarette smoking, NSAID consumption, endoscopic evidence of rebleeding, mean hemoglobin and mean BUN levels on admission, duration of hospitalization and the mean time of rebleeding. However, the need for blood transfusion was much lower in omeprazole than in cimetidine group (mean: 1.68 versus 3.58 units, respectively; p Conclusion This study demonstrated that oral omeprazole significantly excels intravenous cimetidine in reducing the need for blood transfusion and lowering rebleeding rates in patients with upper gastrointestinal bleeding. Though not statistically significant (p = 0.074, shorter periods of hospitalization were found for omeprazole group which merits consideration for cost minimization.

  12. Stability Indicating Liquid Chromatographic Method for Simultaneous determination of Aspirin and Omeprazole.

    Science.gov (United States)

    Patel, Vandana B; Patel, Aishwarya D; Shah, Dimal A

    2017-10-23

    Aspirin combination is prescribed for the its thrombolytic activity where gastric ulceration is the major side effects of aspirin which can be prevented by combining it with proton pump inhibitor omeprazole. Present study describes development of analytical method for the estimation of aspirin and omeprazole in combination. Objective of the present study was to develop and validate chromatographic method for simultaneous analysis of aspirin and omeprazole. Isocratic, reversed phase stability indicating liquid chromatographic method was developed for the simultaneous determination of Aspirin and Omeprazole in combination. The separation was achieved on a Thermo Scientific Hypersil ODS (250 x 4.6 mm, 5 µm) column, kept at ambient temperature, using acetonitrile: methanol: 0.05 M phosphate buffer (40:5:55; pH 4 adjusted with 0.1% tri ethyl amine) as a mobile phase at a flow rate of 1 mL/min and UV detection was performed at 225 nm. The retention time was found to be 3.9 min for aspirin and 5.3 min for omeprazole. The method was oberved to be linear in the range of 2 - 80 μg/mL for aspirin and 1 - 40 μg/mL for omeprazole, respectively. The proposed method was validated as per ICH guidelines Q2 (R1). The developed RP- HPLC method was successfully applied for the simultaneous estimation of aspirin and omeprazole in the presence of degradation products of both the drugs. The present study describes liquid chromatographic method for the estimation of aspirin and omeprzole in combination. The method can be used for the analysis of stability samples and routine quality control samples. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  13. Efficacy of aspirin (325 mg) + omeprazole (40 mg) in treating coronary artery disease.

    Science.gov (United States)

    Sharma, Tushar; Bliden, Kevin; Chaudhary, Rahul; Tantry, Udaya; Gurbel, Paul A

    2017-01-01

    Aspirin is indicated for primary and secondary prevention of cardiovascular diseases (CVD) by major guidelines. However, its use may be associated with gastrointestinal (GI) toxicities, including, but not limited to, GI bleeding. This may lead to increased morbidity and mortality, as well as diminished compliance, which again leads to increased risk of major cardiovascular events. Modified formulations of aspirin often have comparable risks of GI toxicity despite their dose or formulation and have had limited success to prevent GI toxicities. Simultaneous treatment with Proton pump inhibitors (PPIs) has been used successfully to prevent GI toxicities from aspirin. However, addition of an extra medication may lead to lower compliance and hence ineffective or less than optimal treatment. Areas covered: After a selective literature search, a brief review of the available evidence regarding GI toxicity of aspirin and the protective effects of PPIs was conducted. The concept of combination tablets, and the available data about Aralez Pharmaceuticals' YOSPRALA (aspirin (81 mg or 325 mg) and omeprazole (40 mg) fixed dose combination tablet being evaluated for secondary prevention of cardiovascular and cerebrovascular events in patients at risk for GI complications of aspirin therapy) is also presented. Expert opinion: The available evidence suggests that PPIs are the best option to prevent aspirin-related GI toxicities, but compliance is low in people who are prescribed both aspirin and PPI. Combination tablets containing both aspirin and a PPI may be a good option for providing protection against GI toxicities in people who require aspirin for secondary prevention of cardiovascular diseases.

  14. Synergy of Omeprazole and Praziquantel In Vitro Treatment against Schistosoma mansoni Adult Worms.

    Directory of Open Access Journals (Sweden)

    Giulliana T Almeida

    Full Text Available Treatment and morbidity control of schistosomiasis relies on a single drug, praziquantel (PZQ, and the selection of resistant worms under repeated treatment is a concern. Therefore, there is a pressing need to understand the molecular effects of PZQ on schistosomes and to investigate alternative or synergistic drugs against schistosomiasis.We used a custom-designed Schistosoma mansoni expression microarray to explore the effects of sublethal doses of PZQ on large-scale gene expression of adult paired males and females and unpaired mature females. We also assessed the efficacy of PZQ, omeprazole (OMP or their combination against S. mansoni adult worms with a survival in vitro assay.We identified sets of genes that were affected by PZQ in paired and unpaired mature females, however with opposite gene expression patterns (up-regulated in paired and down-regulated in unpaired mature females, indicating that PZQ effects are heavily influenced by the mating status. We also identified genes that were similarly affected by PZQ in males and females. Functional analyses of gene interaction networks were performed with parasite genes that were differentially expressed upon PZQ treatment, searching for proteins encoded by these genes whose human homologs are targets of different drugs used for other diseases. Based on these results, OMP, a widely prescribed proton pump inhibitor known to target the ATP1A2 gene product, was chosen and tested. Sublethal doses of PZQ combined with OMP significantly increased worm mortality in vitro when compared with PZQ or OMP alone, thus evidencing a synergistic effect.Functional analysis of gene interaction networks is an important approach that can point to possible novel synergistic drug candidates. We demonstrated the potential of this strategy by showing that PZQ in combination with OMP displayed increased efficiency against S. mansoni adult worms in vitro when compared with either drug alone.

  15. Omeprazole, Furazolidone, and Tetracycline: an eradication treatment for resistant H. pylori in Brazilian patients with peptic ulcer disease

    Directory of Open Access Journals (Sweden)

    Silva Fernando Marcuz

    2002-01-01

    Full Text Available OBJECTIVES: To determine the efficacy of a simple, short-term and low-cost eradication treatment for Helicobacter pylori (H. pylori using omeprazole, tetracycline, and furazolidone in a Brazilian peptic ulcer population, divided into 2 subgroups: untreated and previously treated for the infection. PATIENTS AND METHODS: Patients with peptic ulcer disease diagnosed by endoscopic examination and infected by H. pylori diagnosed by the rapid urease test (RUT and histological examination, untreated and previously unsuccessfully treated by macrolides and nitroimidazole, were medicated with omeprazole 20 mg daily dose and tetracycline 500 mg and furazolidone 200 mg given 3 times a day for 7 days. Another endoscopy or a breath test was performed 12 weeks after the end of treatment. Patients were considered cured of the infection if a RUT and histologic examination proved negative or a breath test was negative for the bacterium. RESULTS: Sixty-four patients were included in the study. The women were the predominant sex (58%; the mean age was 46 years. Thirty-three percent of the patients were tobacco users, and duodenal ulcer was identified in 80% of patients. For the 59 patients that underwent follow-up examinations, eradication was verified in 44 (75%. The eradication rate for the intention-to-treat group was 69%. The incidence of severe adverse effects was 15%. CONCLUSION: The treatment provides good efficacy for H. pylori eradication in patients who were previously treated without success, but it causes severe adverse effects that prevented adequate use of the medications in 15% of the patients.

  16. Omeprazole increases the efficacy of a soluble epoxide hydrolase inhibitor in a PGE2 induced pain model

    International Nuclear Information System (INIS)

    Goswami, Sumanta Kumar; Inceoglu, Bora; Yang, Jun; Wan, Debin; Kodani, Sean D.; Trindade da Silva, Carlos Antonio; Morisseau, Christophe; Hammock, Bruce D.

    2015-01-01

    Epoxyeicosatrienoic acids (EETs) are potent endogenous analgesic metabolites produced from arachidonic acid by cytochrome P450s (P450s). Metabolism of EETs by soluble epoxide hydrolase (sEH) reduces their activity, while their stabilization by sEH inhibition decreases both inflammatory and neuropathic pain. Here, we tested the complementary hypothesis that increasing the level of EETs through induction of P450s by omeprazole (OME), can influence pain related signaling by itself, and potentiate the anti-hyperalgesic effect of sEH inhibitor. Rats were treated with OME (100 mg/kg/day, p.o., 7 days), sEH inhibitor TPPU (3 mg/kg/day, p.o.) and OME (100 mg/kg/day, p.o., 7 days) + TPPU (3 mg/kg/day, p.o., last 3 days of OME dose) dissolved in vehicle PEG400, and their effect on hyperalgesia (increased sensitivity to pain) induced by PGE 2 was monitored. While OME treatment by itself exhibited variable effects on PGE 2 induced hyperalgesia, it strongly potentiated the effect of TPPU in the same assay. The significant decrease in pain with OME + TPPU treatment correlated with the increased levels of EETs in plasma and increased activities of P450 1A1 and P450 1A2 in liver microsomes. The results show that reducing catabolism of EETs with a sEH inhibitor yielded a stronger analgesic effect than increasing generation of EETs by OME, and combination of both yielded the strongest pain reducing effect under the condition of this study. - Highlights: • The soluble epoxide hydrolase (sEH) inhibitor TPPU is anti-hyperalgesic. • Omeprazole potentiates the anti-hyperalgesic actions of TPPU. • This potentiation is associated with increased P450 activity. • The potentiation is associated with an increase in fatty acid epoxide/diol ratio. • Joint use of sEH inhibitors and P450 inducers could result in drug–drug interactions.

  17. Effects of long-term acid suppressants with ranitidine and omeprazole on gastric mucosa

    Directory of Open Access Journals (Sweden)

    P C Alexander

    2013-01-01

    Full Text Available Background and objectives: Proton pump inhibitors are used widely for gastroesophageal reflux disease and ulcer type dyspepsia. Majority of the patients require long term medication. H2 receptor antagonist are also used for relief of symptoms. Though tachyphylaxis has been reported, symptom response is seen with long term use. The aim of the present study was to study the effects of long-term acid suppressants on gastric antral histology. Methods: Patients who received long-term acid suppressants such as ranitidine and omeprazole for gastroesophageal reflux disease or dyspepsia were included. All of them had an antral biopsy for histology and H. pylori status at baseline, at 6 months and 12 months. Patients on acid suppressants for less than a year or on long-term non-steroidal anti inflammatory drugs were excluded from the study. The grading of gastritis was classified as chronic active gastritis, atrophic gastritis, intestinal metaplasia and dysplasia. Results: Thirty patients received ranitidine and 28 omeprazole. In H. pylori positive group, the median duration of ranitidine and omeprazole were 3 years (1.5 to 8 years and 4 years (1 to 10 years respectively. Two thirds of patients had chronic active gastritis (ranitidine: 35.5%; omeprazole:26.6%; 10 had gastric atrophy (ranitidine: 6.6%; omeprazole:15.5% and 7 had intestinal metaplasia (ranitidine4.4%; omeprazole11.1%. Four of the 10 patients on omeprazole showed progression of histology as against only one of the 13 patients on ranitidine at one year of follow up. In omeprazole pylori negative patients, the median duration of ranitidine and omeprazole was 2.5 years (range 1 to 6 years and 3 years (range 2 to 7 years respectively. Irrespective of the acid suppressants, the baseline histology was either chronic active gastritis (78.5% or gastric atrophy (21.5%. None had intestinal metaplasia. Also there was no progression in histology staging during the follow up. Conclusions: Long-term acid

  18. Peak distortion in the column liquid chromatographic determination of omeprazole dissolved in borax buffer.

    Science.gov (United States)

    Arvidsson, T; Collijn, E; Tivert, A M; Rosén, L

    1991-11-22

    Injection of a sample containing omeprazole dissolved in borax buffer (pH 9.2) into a reversed-phase liquid chromatographic system consisting of a mixture of acetonitrile and phosphate buffer (pH 7.6) as the mobile phase and a C18 surface-modified silica as the solid phase resulted under special conditions in split peaks of omeprazole. The degree of peak split and the retention time of omeprazole varied with the concentration of borax in the sample solution and the ionic strength of the mobile phase buffer as well as with the column used. Borax is eluted from the column in a broad zone starting from the void volume of the column. The retention is probably due to the presence of polyborate ions. The size of the zone varies with the concentration of borax in the sample injected. In the borax zone the pH is increased compared with the pH of the mobile phase, and when omeprazole (a weak acid) is co-eluting in the borax zone its retention is affected. In the front part and in the back part of the borax zone, pH gradients are formed, and these gradients can induce the peak splitting. When the dissolving medium is changed to a phosphate buffer or an ammonium buffer at pH 9 no peak distortion of omeprazole is observed.

  19. Omeprazole (20 mg o.m.) versus ranitidine (150 mg b.d.) in duodenal ulcer healing and pain relief

    NARCIS (Netherlands)

    Mulder, C. J.; Tijtgat, G. N.; Cluysenaer, O. J.; Nicolai, J. J.; Meyer, W. W.; Hazenberg, B. P.; Vogten, A. J.; Gerrits, C.; Stuifbergen, W. H.

    1989-01-01

    The object of this double-blind, multicentre study was to compare duodenal ulcer healing rates after 2 to 4 weeks of treatment with either 20 mg omeprazole o.m. or 150 mg ranitidine b.d. One hundred and eighty-one patients were randomized: 91 received omeprazole and 90 received ranitidine. In a per

  20. Omeprazole, a specific inhibitor of gastric (H+-K+)-ATPase, is a H+-activated oxidizing agent of sulfhydryl groups

    International Nuclear Information System (INIS)

    Im, W.B.; Sih, J.C.; Blakeman, D.P.; McGrath, J.P.

    1985-01-01

    Omeprazole (5-methoxy-2-[[(4-methoxy-3,5- dimethylpyridinyl)methyl]sulfinyl]-1H-benzimidazole) appeared to inhibit gastric (H + -K + )-ATPase by oxidizing its essential sulfhydryl groups, since the gastric ATPase inactivated by the drug in vivo or in vitro recovered its K+-dependent ATP hydrolyzing activity upon incubation with mercaptoethanol. Biological reducing agents like cysteine or glutathione, however, were unable to reverse the inhibitory effect of omeprazole. Moreover, acidic environments enhanced the potency of omeprazole. The chemical reactivity of omeprazole with mercaptans is also consistent with the biological action of omeprazole. The N-sulfenylated compound reacted at neutral pH with another stoichiometric amount of ethyl mercaptan to produce omeprazole sulfide quantitatively. The gastric polypeptides of 100 kilodaltons representing (H + -K + )-ATPase in the rat gastric mucosa or isolated hog gastric membranes were covalently labeled with [ 14 C]omeprazole. The radioactive label bound to the ATPase, however, could not be displaced by mercaptoethanol under the identical conditions where the ATPase activity was fully restored. These observations suggest that the essential sulfhydryl groups which reacted with omeprazole did not form a stable covalent bond with the drug, but rather that they further reacted with adjacent sulfhydryl groups to form disulfides which could be reduced by mercaptoethanol

  1. Effects of CYP2C19 Genetic Polymorphisms on PK/PD Responses of Omeprazole in Korean Healthy Volunteers.

    Science.gov (United States)

    Park, Sunny; Hyun, Yang Jin; Kim, Yu Ran; Lee, Ju Hyun; Ryu, Sunae; Kim, Jeong Mi; Oh, Woo Yong; Na, Han Sung; Lee, Jong Gu; Seo, Doo Won; Hwang, In Yeong; Park, Zewon; Jang, In Jin; Oh, Jaeseong; Choi, Seung Eun

    2017-05-01

    The aim of this study was to examine the effects of CYP2C19*2 and *3 genetic polymorphisms on omeprazole pharmacokinetic (PK) and pharmacodynamic (PD) responses. Twenty-four healthy Korean volunteers were enrolled and given 20 mg omeprazole orally once daily for 8 days. The genotypes of CYP2C19 single nucleotide polymorphisms (SNPs) (*2, *3, and *17) were screened. The plasma concentrations of omeprazole, omeprazole sulfone, and 5-hydroxy (5-OH) omeprazole were determined by liquid chromatography with tandem mass spectrometry (LC-MS/MS). The noncompartmental method was used for the determination of PK parameters. Change of mean pH and proportion (%) of time of gastric pH above 4.0 were estimated. The poor metabolizer (PM) group had the lowest metabolic ratio and exhibited the highest area under the curve (AUC) for omeprazole among the CYP2C19 phenotype groups. The PM group showed the greatest change of mean pH and the highest % time of gastric pH above 4.0. The relationship between AUC of omeprazole and % time of gastric pH above 4.0 was confirmed. The study demonstrates that CYP2C19*2 and *3 influence the PKs and PDs of omeprazole in Korean healthy volunteers. © 2017 The Korean Academy of Medical Sciences.

  2. New chromatographic method for separating Omeprazole from its degradation components and the quantitatively determining it in its pharmaceutical products

    International Nuclear Information System (INIS)

    Touma, M.; Rajab, A.; Seuleiman, M.

    2007-01-01

    New chromatographic method for Quantitative Determination of Omeprazole in its Pharmaceutical Products was produced. Omeprazole and its degradation components were well separated in same chromatogram by using high perfume liquid chromatography (HPLC). The new analytical method has been validated by these characteristic tests (accuracy, precision, range, linearity, specificity/selectivity, limit of detection (LOD) and limit of quantitative (LOQ) ).(author)

  3. Efficacy of omeprazole on cough, pulmonary function and quality of life of patients with sulfur mustard lung injury: A placebo-control, cross-over clinical trial study

    Directory of Open Access Journals (Sweden)

    Mohammad Hossein Emami

    2014-01-01

    Full Text Available Background: Gastro-esophageal reflux disease (GERD is prevalent and related to more severe disease in patients with respiratory problems. We evaluated the effects of antireflux therapy in warfare victims of exposure to Mustard gas with chronic cough. Materials and Methods: This randomized, double-blind, placebo-controlled, cross-over study was conducted on 45 cases of sulfur mustard injury with chronic cough (≥8 weeks and GERD. Patients were randomized into two groups, receiving either 20 mg twice daily omeprazole-placebo (OP or matching placebo (placebo-omeprazole [PO] for 4 months, followed by a 1-month washout period and the alternative treatment for 4 months. Assessments included GERD and cough, quality of life, and pulmonary function using spirometry. Leicester Cough Questionnaire and SF-36 were used for measuring quality of life. Results: Patients in the OP group experienced a more decrease than those in the PO group in severity of Leicester cough scores during the first 4-month of trial. After crossing the groups, the OP group experienced an increase (P = 0.036 and the PO group experienced a nonsignificant decrease (P = 0.104 in the severity of scores. The OP group also experienced improvement in GERD symptoms and quality of life at the end of the trial, but changes in the PO group was not significant. There was no significant change in respiratory function indices in any groups. Conclusion: Long-term treatment with high-dose omeprazole improved GERD as well as cough, and quality of life, but not changed respiratory function indices in sulfur mustard injured cases with respiratory symptoms.

  4. Changes in gefitinib, erlotinib and osimertinib pharmacokinetics under various gastric pH levels following oral administration of omeprazole and vonoprazan in rats.

    Science.gov (United States)

    Yasumuro, Osamu; Uchida, Shinya; Kashiwagura, Yasuharu; Suzuki, Ayae; Tanaka, Shimako; Inui, Naoki; Watanabe, Hiroshi; Namiki, Noriyuki

    2017-11-17

    1. Although drug interactions between epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and gastric acid-suppressing medications (AS) are considered clinically significant, there is limited data regarding the influence of various gastric pH conditions on the pharmacokinetics of EGFR-TKIs. We aimed to clarify the changes in the pharmacokinetics of the EGFR-TKIs, gefitinib, erlotinib and osimertinib, due to the changes in gastric pH after administration of omeprazole or vonoprazan. 2. Omeprazole (10-100 mg/kg, p.o.) and vonoprazan (1-5 mg/kg, p.o.) led to a significant and dose-dependent increase in gastric pH. 3. AUC 0-3 of gefitinib and erlotinib (5 mg/kg, p.o.) started to decrease at gastric pH 3.3 and 5.6, respectively, reached a plateau at pH > 6, and then significantly decreased up to 47 and 59% of control levels, respectively. AUC 0-3 of osimertinib (5 mg/kg, p.o.) was not significantly changed by omeprazole and vonoprazan. 4. Although there are some issues regarding the extrapolation of the results of our rat study to humans, careful monitoring of patients treated with gefitinib and erlotinib is needed in cases in which the gastric pH increases from 3 to 5 and especially when the gastric pH is >5 in patients who are co-administered both the EGFR-TKIs and AS.

  5. Assessment of Pharmacokinetic Interactions Between Obeticholic Acid and Caffeine, Midazolam, Warfarin, Dextromethorphan, Omeprazole, Rosuvastatin, and Digoxin in Phase 1 Studies in Healthy Subjects.

    Science.gov (United States)

    Edwards, Jeffrey E; Eliot, Lise; Parkinson, Andrew; Karan, Sharon; MacConell, Leigh

    2017-09-01

    Obeticholic acid (OCA), a potent and selective farnesoid X receptor agonist, is indicated for the treatment of primary biliary cholangitis (PBC). We investigated the potential drug-drug interaction effect of OCA on metabolic CYP450 enzymes and drug transporters. Five phase 1 single-center, open-label, fixed-sequence, inpatient studies were conducted in healthy adult subjects to evaluate the effect of oral daily doses of 10 or 25 mg OCA on single-dose plasma pharmacokinetics of specific probe substrates for enzymes CYP1A2 (caffeine, R-warfarin), CYP3A (midazolam, R-warfarin), CYP2C9 (S-warfarin), CYP2D6 (dextromethorphan), CYP2C19 (omeprazole), and drug transporters, BCRP/OATP1B1/OATP1B3 (rosuvastatin), and P-gp (digoxin). OCA showed no substantial suppression/inhibition of S-warfarin, digoxin, and dextromethorphan and weak interactions with caffeine, omeprazole, rosuvastatin, and midazolam. The maximal pharmacodynamic responses (E max ) to warfarin-based INR, PT, and aPTT were reduced by 11%, 11%, and 1%, respectively, for the 10-mg dose group and by 7%, 7% and 0%, respectively, for the 25-mg dose group. Overall, drugs dosed in combination with OCA were well tolerated, and most adverse events were mild in severity. No clinically important trends were noted in laboratory evaluations, vital signs, or 12-lead ECGs. In these studies, OCA showed weak to no suppression/inhibition of metabolic enzymes and drug transporters at the highest recommended therapeutic dose in patients with PBC. On the basis on these analyses, monitoring and maintenance of target INR range are required during coadministration of OCA with drugs that are metabolized by CYP1A2 (R-warfarin). Intercept Pharmaceuticals, Inc.

  6. Regioselective C-H hydroxylation of omeprazole sulfide by Bacillus megaterium CYP102A1 to produce a human metabolite.

    Science.gov (United States)

    Jang, Hyun-Hee; Ryu, Sang-Hoon; Le, Thien-Kim; Doan, Tiep Thi My; Nguyen, Thi Huong Ha; Park, Ki Deok; Yim, Da-Eun; Kim, Dong-Hyun; Kang, Choong-Kyung; Ahn, Taeho; Kang, Hyung-Sik; Yun, Chul-Ho

    2017-01-01

    To find a simple enzymatic strategy for the efficient synthesis of the expensive 5'-hydroxyomeprazole sulfide, a recently identified minor human metabolite, from omeprazole sulfide, which is an inexpensive substrate. The practical synthetic strategy for the 5'-OH omeprazole sulfide was accomplished with a set of highly active CYP102A1 mutants, which were obtained by blue colony screening from CYP102A1 libraries with a high conversion yield. The mutant and even the wild-type enzyme of CYP102A1 catalyzed the high regioselective (98 %) C-H hydroxylation of omeprazole sulfide to 5'-OH omeprazole sulfide with a high conversion yield (85-90 %). A highly efficient synthesis of 5'-OH omeprazole sulfide was developed using CYP102A1 from Bacillus megaterium as a biocatalyst.

  7. Comparing the Effect of Psyllium Seed on Gastroesophageal Reflux Disease With Oral Omeprazole in Patients With Functional Constipation.

    Science.gov (United States)

    Hosseini, Mousalreza; Salari, Roshanak; Akbari Rad, Mina; Salehi, Maryam; Birjandi, Batul; Salari, Masoumeh

    2018-01-01

    Gastroesophageal reflux disease (GERD) is one of the most common gastrointestinal diseases. Several studies have been carried out on the treatment of symptoms associated with GERD. The present study aimed to compare the effect of Psyllium seed and oral omeprazole on GERD in patients with functional constipation. In this trial, 132 patients were divided into 2 groups. The impact of omeprazole and Psyllium seed on the treatment and recurrence of GERD was studied. Among the patients, the rate of response to treatment was 89.2% (n = 58) in the Psyllium seed group, while in omeprazole group, it was 94% (n = 63; P = .31). The recurrence rates of Psyllium seed and omeprazole groups were 24.1% (n =14) and 69.8% (n = 44), respectively ( P < .001). The results showed that treatment of functional constipation by Psyllium seed in patients with GERD leads to improvement of GERD and its recurrences in comparison with omeprazole.

  8. Enantioselective analysis of omeprazole in pharmaceutical formulations by chiral high-performance liquid chromatography and capillary electrophoresis

    Directory of Open Access Journals (Sweden)

    Bonato Pierina S.

    2004-01-01

    Full Text Available We developed two sensitive and simple assay procedures based on high- performance liquid chromatography and capillary electrophoresis (CE for the enantioselective analysis of omeprazole in pharmaceutical formulations. Rac-omeprazole and (S-omeprazole were extracted from commercially available tablets using methanol:NaOH 2.5 mol L-1 (90:10, v/v. Chiral HPLC separation of omeprazole was obtained on a CHIRALPAK AD column using hexane:ethanol (40:60, v/v as the mobile phase and detection at 302 nm. The resolution of omeprazole enantiomers by CE was carried out using 3% sulfated beta-cyclodextrin in 20 mmol L-1 phosphate buffer, pH 4.0 and detection at 202 nm.

  9. The effects of omeprazole therapy on bacterial colonization of the pharynx in healthy dogs.

    Science.gov (United States)

    Sullivan, Lauren A; Wakayama, Justin; Boscan, Pedro L; Hyatt, Doreene R; Twedt, David C; Lappin, Michael R; Dargatz, David A

    2016-01-01

    To identify the relative abundance of commensal pharyngeal flora in healthy dogs and determine if abundance of pharyngeal flora is altered during omeprazole administration. Eight adult Beagles. A total of 3 baseline pharyngeal swabs, collected 48 hours apart, were obtained from each dog. Omeprazole (1 mg/kg PO q 24 h) was administered for a total of 12 days. During omeprazole administration, pharyngeal swabs were obtained on Days 8, 10, and 12. All swabs were submitted for semiquantitative aerobic and anaerobic culture. Growth of bacterial isolates, as well as genus of isolates, was compared between the pretreatment (n = 24) and treatment (n = 24) swabs. A greater abundance of several bacterial species was identified during the treatment period, including coagulase-negative Staphylococcus (P therapy. Further studies are warranted to determine the clinical significance of gastric acid suppressants on pharyngeal flora in dogs. © Veterinary Emergency and Critical Care Society 2015.

  10. Reversibility of the cell kinetic changes induced by omeprazole in the rat oxyntic mucosa

    International Nuclear Information System (INIS)

    Tielemans, Y.; Chen, D.; Sundler, F.; Haakanson, R.; Willems, G.

    1992-01-01

    Both oxyntic mucosal progenitor cells and enterochromaffin-like (ECL) cells are under the trophic control of gastrin. The authors studied the effect of discontinuing omeprazole-induced hypergastrinemia on cell proliferation and ECL cell function in the rat oxyntic mucosa. All rats had hypergastrinemia after 16 days omeprazole administration, and the proliferation rate of both progenitor and ECL cells was increased, wheras it was decreased 5 days after withdrawal of omeprazole. Circulating gastrin had normalized by then. The proliferative activity of the progenitor cells returned to normal within 10 days, whereas that of the ECL cells remained suppressed for at least 20 days. The histidine decarboxylase activity of the ECL cells changed in parallel with their proliferative activity. These data suggest either a down-regulation of membrane receptors or the involvement of still unknown inhibitors of mitotic activity and ECL cell function in the oxyntic mucosa. 33 refs., 6 figs

  11. Comparison of outcomes twelve years after antireflux surgery or omeprazole maintenance therapy for reflux esophagitis

    DEFF Research Database (Denmark)

    Lundell, Lars; Miettinen, Pekka; Myrvold, Helge E

    2009-01-01

    BACKGROUND & AIMS: It is important to evaluate the long-term effects of therapies for gastroesophageal reflux disease (GERD). In a 12-year study, we compared the effects of therapy with omeprazole with those of antireflux surgery. METHODS: This open, parallel group study included 310 patients...... with esophagitis enrolled from outpatient clinics in Nordic countries. Of the 155 patients randomly assigned to each arm of the study, 154 received omeprazole (1 withdrew before therapy began), and 144 received surgery (11 withdrew before surgery). In patients who remained in remission after treatment, post......-fundoplication complaints, other symptoms, and safety variables were assessed. RESULTS: Of the patients enrolled in the study, 71 who were given omeprazole (46%) and 53 treated with surgery (37%) were followed for a 12-year follow-up period. At this time point, 53% of patients who underwent surgery remained in continuous...

  12. Peripheral IV Insulin Infusion Infiltration Presenting as "Insulin Resistance".

    Science.gov (United States)

    Kim, Tiffany Y; Woeber, Kenneth A; MacMaster, Heidimarie Windham; Rushakoff, Robert J

    2016-11-01

    We present the case of a 66-year-old woman who developed hypoglycemia following the prolonged infiltration of a high dose continuous peripheral IV insulin infusion. Case report. PubMed was searched for relevant literature on exogenous hyperinsulinemic hypoglycemia. The patient was postlung transplantation and was receiving high doses of glucocorticoids. Despite increasing the peripheral IV insulin rate, hyperglycemia persisted. We discovered that the IV insulin infusion line infiltrated, resulting in a large subcutaneous insulin depot, estimated to be 450 units of regular insulin. She subsequently experienced prolonged hypoglycemia that was managed with concentrated dextrose containing fluids. In our literature search, there were no similar case reports. The literature on insulin overdose, usually from suicide attempts, can help guide the management of iatrogenic hyperinsulinemic hypoglycemia. Important management considerations include anticipated duration of hypoglycemia, supplemental glucose, fluid management, and electrolyte monitoring. Peripheral IV insulin infusion infiltration should be considered when patients do not respond to increasing rates of insulin infusion.

  13. A naturalistic glyceryl trinitrate infusion migraine model in the rat

    DEFF Research Database (Denmark)

    Ramachandran, Roshni; Bhatt, Deepak Kumar; Ploug, Kenneth Beri

    2012-01-01

    Glyceryl trinitrate (GTN) infusion is a reliable method to provoke migraine-like headaches in humans. Previous studies have simulated this human model in anaesthetized or in awake rodents using GTN doses 10,000 times higher than used in humans. The relevance of such toxicological doses to migraine...

  14. Comparison of aloe vera and omeprazole in the treatment of equine gastric ulcer syndrome.

    Science.gov (United States)

    Bush, J; van den Boom, R; Franklin, S

    2018-01-01

    Anecdotally, aloe vera is used to treat gastric ulceration, although no studies have yet investigated its efficacy in horses. To test the hypothesis that aloe vera would be noninferior to omeprazole in the treatment of equine gastric ulcer syndrome. Randomised, blinded clinical trial. Forty horses with grade ≥2 lesions of the squamous and/or glandular mucosa were randomly assigned to one of two groups. Horses received either aloe vera inner leaf gel (17.6 mg/kg bwt) b.i.d. or omeprazole (4 mg/kg bwt) s.i.d. for approximately 28 days, after which a repeat gastroscopic examination was performed to determine disease resolution. Horses with persistent lesions were offered a further 28 days of treatment with omeprazole (4 mg/kg bwt s.i.d.) and were re-examined on completion of treatment. Efficacy analyses were based on 39 horses that completed the trial. Equine squamous gastric disease (ESGD) was observed in 38 horses; improvement and healing rates in these horses were 56% and 17%, respectively, in the aloe vera group, and 85% and 75%, respectively, in the omeprazole group. Healing was less likely to occur in horses with prolonged gastric emptying. Equine glandular gastric disease (EGGD) was less common than ESGD (n = 14) and numbers were too small to perform meaningful statistical analyses. The hypothesis that aloe vera would be noninferior to omeprazole was not supported. No placebo control group was included. Limited numbers preclude any comment on the efficacy of aloe vera in the treatment of EGGD. Treatment with aloe vera was inferior to treatment with omeprazole. © 2017 EVJ Ltd.

  15. Esophagectomy with gastroplasty in advanced megaesophagus: late results of omeprazole use

    Directory of Open Access Journals (Sweden)

    Celso de Castro Pochini

    Full Text Available Objective: To analyze the late results of advanced Chagasic megaesophagus treatment by esophagectomy associated with the use of proton pump inhibitor (omeprazole as for the incidence of esophagitis and Barrett's esophagus in the remaining stump. Methods : We studied patients with advanced megaesophagus undergoing esophagectomy and transmediastinal esophagogastroplasty. Patients were divided into three groups: A (20 with esophageal replacement by full stomach, without the use of omeprazole; B (20 with esophageal replacement by full stomach, with omeprazole 40 mg/day introduced after the first postoperative endoscopy and maintained for six years; and C (30 with esophageal replacement by gastric tube with use of omeprazole. Dysphagia, weight loss and BMI were clinical parameters we analyzed. Upper gastrointestinal endoscopy was performed in all patients, and determined the height of the anastomosis, the aspect of the mucosa, with special attention to possible injuries arising from gastroesophageal reflux, and the patency of the esophagogastric anastomosis. Results : We studied 50 patients, 28 males (56% and 22 (44% females. All underwent endoscopy every year. In the first endoscopy, erosive esophagitis was present in nine patients (18% and Barrett's esophagus, in four (8%; in the last endoscopy, erosive esophagitis was present in five patients (8% and Barrett's esophagus in one (2%. When comparing groups B and C, there was no evidence that the manufacturing of a gastric tube reduced esophagitis and Barrett's esophagus. However, when comparing groups A and C, omeprazole use was correlated with reduction of reflux complications such as esophagitis and Barrett's esophagus (p <0.005. Conclusion : The use of omeprazole (40 mg/day reduced the onset of erosive esophagitis and Barrett's esophagus during the late postoperative period.

  16. Omeprazole suppressed plasma magnesium level and duodenal magnesium absorption in male Sprague-Dawley rats.

    Science.gov (United States)

    Thongon, Narongrit; Penguy, Jirawat; Kulwong, Sasikan; Khongmueang, Kanyanat; Thongma, Matthana

    2016-11-01

    Hypomagnesemia is the most concerned side effect of proton pump inhibitors (PPIs) in chronic users. However, the mechanism of PPIs-induced systemic Mg 2+ deficit is currently unclear. The present study aimed to elucidate the direct effect of short-term and long-term PPIs administrations on whole body Mg 2+ homeostasis and duodenal Mg 2+ absorption in rats. Mg 2+ homeostasis was studied by determining the serum Mg 2+ level, urine and fecal Mg 2+ excretions, and bone and muscle Mg 2+ contents. Duodenal Mg 2+ absorption as well as paracellular charge selectivity were studied. Our result showed that gastric and duodenal pH markedly increased in omeprazole-treated rats. Omeprazole significantly suppressed plasma Mg 2+ level, urinary Mg 2+ excretion, and bone and muscle Mg 2+ content. Thus, omeprazole induced systemic Mg 2+ deficiency. By using Ussing chamber techniques, it was shown that omeprazole markedly suppressed duodenal Mg 2+ channel-driven and Mg 2+ channel-independent Mg 2+ absorptions and cation selectivity. Inhibitors of mucosal HCO 3 - secretion significantly increased duodenal Mg 2+ absorption in omeprazole-treated rats. We therefore hypothesized that secreted HCO 3 - in duodenum decreased luminal proton, this impeded duodenal Mg 2+ absorption. Higher plasma total 25-OH vitamin D, diuresis, and urine PO 4 3- were also demonstrated in hypomagnesemic rats. As a compensatory mechanism for systemic Mg 2+ deficiency, the expressions of duodenal transient receptor potential melastatin 6 (TRPM6), cyclin M4 (CNNM4), claudin (Cldn)-2, Cldn-7, Cldn-12, and Cldn-15 proteins were enhanced in omeprazole-treated rats. Our findings support the potential role of duodenum on the regulation of Mg 2+ homeostasis.

  17. Erroneous formulation of delayed-release omeprazole capsules: alert for importing countries.

    Science.gov (United States)

    Rahman, Mohammad Sofiqur; Yoshida, Naoko; Tsuboi, Hirohito; Keila, Tep; Sovannarith, Tey; Kiet, Heng Bun; Dararth, Eav; Zin, Theingi; Tanimoto, Tsuyoshi; Kimura, Kazuko

    2017-05-03

    Poor drug quality is a matter of serious concern, especially in countries where drug regulation and law enforcement are constrained by limited resources. This study was carried out to investigate the cause of quality failure of omeprazole in Cambodia in 2010 and Myanmar in 2014. We conducted pharmacopoeial quantity, content uniformity and dissolution tests of 156 samples of omeprazole capsules collected in Cambodia in 2010 and Myanmar in 2014. High failure rates were found, especially in dissolution testing, and detailed investigation of several unacceptable samples was carried out by means of in-vitro dissolution profiling, scanning electron microscopy (SEM) and X-ray computed tomography (X-ray CT) to identify the cause of failure. Dissolution profiling with and without the acid stage showed that acid caused premature omeprazole release, indicating that the enteric coating of the omeprazole granules was ineffective. SEM examination of two failed samples revealed cracked and broken granules mixed with apparently intact omeprazole granules in the capsule. X-ray CT examination indicated that some granules of failed samples completely lacked enteric coating, and others had incomplete and non-uniform enteric coating or malformation. Omeprazole capsules collected in Myanmar and Cambodia showed high failure rates in pharmacopoeial tests, especially dissolution tests. Some samples were found to have ineffective or absent enteric coating of the granules, resulting in premature dissolution and degradation in acidic conditions. This is a potentially serious public health issue that needs to be addressed by regulatory authorities in Cambodia and Myanmar, possibly through a collaborative initiative with manufacturers.

  18. Intravenous lidocaine infusion.

    Science.gov (United States)

    Soto, G; Naranjo González, M; Calero, F

    2018-02-26

    Systemic lidocaine used in continuous infusion during the peri-operative period has analgesic, anti-hyperalgesic, as well as anti-inflammatory properties. This makes it capable of reducing the use of opioids and inhalational anaesthetics, and the early return of bowel function, and patient hospital stay. The aim of this narrative review was to highlight the pharmacology and indications for clinical application, along with new and interesting research areas. The clinical applications of peri-operative lidocaine infusion have been reviewed in several recent systematic reviews and meta-analyses in patients undergoing open and laparoscopic abdominal procedures, ambulatory procedures, and other types of surgery. Peri-operative lidocaine infusion may be a useful analgesic adjunct in enhanced recovery protocols. Potential benefits of intravenous lidocaine in chronic post-surgical pain, post-operative cognitive dysfunction, and cancer recurrence are under investigation. Due to its immunomodulation properties over surgical stress, current evidence suggests that intravenous lidocaine could be used in the context of multimodal analgesia. Copyright © 2018 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

  19. Standard concentration infusions in paediatric intensive care: the clinical approach.

    Science.gov (United States)

    Perkins, Joanne; Aguado-Lorenzo, Virginia; Arenas-Lopez, Sara

    2017-05-01

    The use of standard concentrations of intravenous infusions has been advocated by international organisations to increase intravenous medication safety in paediatric and neonatal critical care. However, there is no guidance on how to identify and implement these infusions leading to great interunit variability. To identify the most appropriate clinical concentrations required by our paediatric intensive care unit (PICU) population with regard to accuracy of delivery and overall fluid allowance. Firstly a matrix was used to balance the concentration, dose and infusion volume (weight range 1.5-50 kg). Results were further refined considering: patient fluid allowance based on fluid volume targets, infusion pump accuracy and challenging each infusion against clinical scenarios requiring administration of multiple drug infusions found in PICU. Consideration was given to the standard concentrations routinely used in adults, in order to assess whether alignment with paediatrics was possible for some of the concentrations proposed. Finally a risk assessment of the infusions was conducted using the NPSA 20 tool. Twenty-five drugs identified as the most commonly used intravenous infusions in the unit. For the majority of the medicines, three weight bands of standard concentrations were necessary to cover the children's weight ranges and kept within predefined fluid requirements and accuracy of delivery. This work shows a patient focused systematic approach for defining and evaluating standardised concentrations in intensive care children. © 2016 Royal Pharmaceutical Society.

  20. Disposition kinetics of omeprazole in healthy female volunteers in Faisalabad.

    Science.gov (United States)

    Ashraf, Sadia; Khaliq, Tanweer; Javed, Ijaz; Aslam, Bilal; Qadir, Nazia; Noor, Nadia

    2018-01-01

    Omeprazole (OMP) a proton pump inhibitor is widely used to suppress gastric acid secretions of parietal cells of stomach and metabolized predominantly by CYP2C19. The objective of the present study was to investigate the pharmacokinetics and dosage regimen of OMP, after its single oral administration in eight healthy adult female subjects. Blood samples were collected at different time intervals after oral administration and their pH was measured. Plasma concentration of OMP was determined by high performance liquid chromatography (HPLC) system equipped with UV-visible Detector. The concentration versus time data was used to compute the pharmacokinetic parameters with the help of computer software programme MW/PHRAM APO version 3.02.Peak plasma concentration was (C max ) 0.38±0.04 μg/ml achieved at 2.07±0.22 hrs. The elimination half-life (t 1/2 β) was1.82 ± 0.42 hrs. Volume of distribution (Vd) in the present study was 0.40 ± 0.07 l/kg with total body clearance (Cl B ) 0.19 ± 0.02 l/hr/kg and area under the curve (AUC) 1.89 ± 0.23 μg.hr/ml.The pharmacokinetic properties which are different from the literature after oral administration of 20 mg OMP in eight healthy female volunteers may be due to the variations of environment and genetic variation between Pakistan and drug manufacturing of foreign countries.

  1. Quality of omeprazole purchased via the Internet and personally imported into Japan: comparison with products sampled in other Asian countries.

    Science.gov (United States)

    Rahman, Mohammad Sofiqur; Yoshida, Naoko; Sugiura, Sakura; Tsuboi, Hirohito; Keila, Tep; Kiet, Heng Bun; Zin, Theingi; Tanimoto, Tsuyoshi; Kimura, Kazuko

    2018-03-01

    To evaluate the quality of omeprazole personally imported into Japan via the Internet and to compare the quality of these samples with previously collected samples from two other Asian countries. The samples were evaluated by observation, authenticity investigation and pharmacopoeial quality analysis. Quality comparison of some selected samples was carried out by dissolution profiling, Raman spectroscopy and principle component analysis (PCA). Observation of the Internet sites and samples revealed some discrepancies including the delivery of a wrong sample and the selling of omeprazole without a prescription, although it is a prescription medicine. Among the 28 samples analysed, all passed the identification test, 26 (93%) passed the quantity and content uniformity tests and all passed the dissolution test. Dissolution profiling confirmed that all the personally imported omeprazole samples remained intact in the acid medium. On the other hand, six samples from two of the same manufacturers, previously collected during surveys in Cambodia and Myanmar, frequently showed premature omeprazole release in acid. Raman spectroscopy and PCA showed significant variation between omeprazole formulations in personally imported samples and the samples from Cambodia and Myanmar. Our results indicate that the pharmaceutical quality of omeprazole purchased through the Internet was sufficient, as determined by pharmacopeial tests. However, omeprazole formulations distributed in different market segments by the same manufacturers were of diverse quality. Measures are needed to ensure consistent quality of products and to prevent entry of substandard products into the legitimate supply chain. © 2018 The Authors. Tropical Medicine & International Health Published by John Wiley & Sons Ltd.

  2. Perbandingan Efektivitas antara Omeprazol dan Lansoprazol terhadap Perbaikan Kualitas Hidup Penderita Rinosinusitis Kronik Akibat Refluks Laringofaring

    Directory of Open Access Journals (Sweden)

    Tantri Kurniawati

    2012-09-01

    Full Text Available Laryngopharyngeal reflux (LPR is the reflux of gastric acid through the esophagus that reaches laringopharyngeal area. The prevalence of LPR in the range 15–20%, and caused chronic rhinosinusitis (CRS. The incidence of LPR in patients with CRS has ranged between 37–72%. The prevalence of CRS 16,3% in adults and affecting quality of life. Omeprazole and lansoprazole are proton pump inhibitors (PPIs for LPR’s therapy and also a therapy for CRS with LPR as the etiology. This research method was randomized clinical trial with open trial observation, conducted in June to December 2009. Twenty subjects with consecutive sampling method, divided into two groups (with simple randomization, the first group received omeprazole and the other lansoprazole. The subjects conducted complete physical otolaryngology examination, sino-nasal outcome test 20, reflux symptom index and reflux finding score with fiber optic rhinolaryngoscopy. These data was obtained before therapy, after 2 weeks and two months therapy, analyzed with Wilcoxon’s and Mann-Whitney’s test. There was no effectivity difference between omperazole and lansoprazole in reducing the level of severity of LPR (p>0.05, but quality of life improvement was better in lansoprazole than omeprazole group (p<0.05. In conclusion, lansoprazole is more effective than omeprazole in improvement of quality of life in patients with chronic rhinosinusitis caused by LPR

  3. [Reflux esophagitis: a comparative study of lansoprazole and omeprazole as short-term therapy. Preliminary report].

    Science.gov (United States)

    Córdova-Villalobos, J A; Ramírez-Barba, E J; Ramírez-Covarrubias, J C

    1996-01-01

    Reflux Esophagitis is a common complaint from the upper gastrointestinal tract with a figured out prevalence of about 2%. Therapeutic results in this pathology have been unsatisfactory. To compare lansoprazole and omeprazole therapeutic effects in patients with reflux esophagitis. A clinical, double-blinded, balanced survey was randomly designed with patients who would daily receive 30 mg lansoprazole (Group A) or 20 mg omeprazole (Group B) during a 4-week period. All patients were submitted to endoscopy and biopsy both at the beginning and at the end of the survey. Ten patients in each group were treated without any significant differences in sex, age, nicotinism, alcoholism, AINES ingestion, development time, pain regurgitations, pyrrosis, hematemesis, dysphagia, melena, nausea or vomiting, and esophagitis degree. A complete cure in 8/10 (omeprazole) and 7/10 (lansoprazole) patients was obtained (p = n.s.). However, the histological results of the biopsy at the end of the four-week period proved to be a failure in 4/10 (omeprazole) and in 5/10 (lansoprazole) patients (p = n.s.). The endoscopy and clinical result at the end of the study were similarly effective; but not so the histological damage to the esophagus, which continues to be important. The use of bomb inhibitors in esophagitis by reflux is advisable. Future surveys must assess the average time of treatment for the disappearance of the histologic lesion.

  4. Pharmacokinetics and tolerability of a new formulation of omeprazole in the horse.

    Science.gov (United States)

    Di Salvo, A; Busechian, S; Zappulla, F; Marchesi, M C; Pieramati, C; Orvieto, S; Boveri, M; Predieri, P G; Rueca, F; Della Rocca, G

    2017-08-01

    A new formulation of omeprazole in gastro-resistant granules was tested with regard to its pharmacokinetics and tolerability. Twenty-four horses were randomly divided into three groups (8 horses/group) and treated, according a parallel study design, as follows: Group A untreated (control group), Group B received 4 mg/kg of omeprazole, and Group C received 12 mg/kg of omeprazole, both of which were treated orally once a day for 90 days. Blood samples, taken from Group B subjects during the 1st and the 29th day of treatment at pre-established time points, were used to determine the concentration-time curves of omeprazole. The treatments were found to be safe and well tolerated by the horses. The serum hematological and biochemical values were within reference ranges for the entire observational time. No accumulation of the drug was found after 29 days of treatment. Lower C max and AUCs were obtained at the 29th day of treatment. © 2016 John Wiley & Sons Ltd.

  5. Theoretical Investigation of Inclusion Complex between Omeprazole Enantiomers and Carboxymethyl-β-Cyclodextrin

    Science.gov (United States)

    Setiadji, S.; Sundari, C. D. D.; Ramdhani, M. A.; Umam, A. B. K.; Ivansyah, A. L.

    2018-01-01

    Host-guest inclusion complexes between R/S-Omeprazole (R/S-OME) enantiomers with Carboxymethyl-β-Cyclodextrin (CM-β-CD) is proposed to predicts the separation of its enantiomers that considering the interaction energy and inclusion geometry. The inclusion complex structures were built into two orientations i.e. 1: 1 and 2: 1 as the ratio of host to guest. All structures were optimized by two methods i.e. molecular mechanic docking and quantum semi empiric PM3. Based on the value of binding energy obtained from the computational modelling, it was found that inclusion complex of S-Omeprazole with Carboxymethyl-β-Cyclodextrin (S-OME/CM-β-CD) is more stable than the inclusion complex of R-Omeprazole with Carboxymethyl-β-Cyclodextrin (R-OME/CM-β-CD). Moreover, R/S-Omeprazole can form stable inclusion complexes with Carboxymethyl-β-Cyclodextrin by the ratio of host: guest equal to 2: 1. Other thermodynamic parameter values, i.e. Enthalpy (ΔH), Entropy (ΔS), and Gibbs free energy (ΔG) show that the inclusion complex of S-OME/CM-β-CD is more exothermic, more spontaneous, and preferably formed when compared to inclusion complex of R-OME/CM-β-CD. In addition, the formation of the R/S-OME inclusion complex with Carboxymethyl-β-Cyclodextrin (CM-β-CD) is an enthalpy driven process based on these values.

  6. Comparative effects of adjuvant cimetidine and omeprazole during pancreatic enzyme replacement therapy

    NARCIS (Netherlands)

    Bruno, M. J.; Rauws, E. A.; Hoek, F. J.; Tytgat, G. N.

    1994-01-01

    In a double-blind, randomized crossover study, the hypotheses were tested that more powerful inhibition of gastric acid secretion by adjuvant omeprazole further improves the efficacy of pancreatic enzyme replacement therapy compared to adjuvant cimetidine and that excluding the influence of

  7. [Immediate type reactions to proton pump inhibitors using pantoprazole and omeprazole as examples].

    Science.gov (United States)

    Dohr, J; Hunzelmann, N; Brown, A

    2018-02-01

    Proton pump inhibitors (PPIs) belong to the most frequently taken drugs worldwide. Hypersensitivity to these medications is rare, but can lead to severe immediate type reactions. Especially cross-reactivity between the different PPIs can occur. In this case series, we describe 4 patients with immediate type reactions to pantoprazole and/or omeprazole.

  8. EFEITO DA RANITIDINA E DO OMEPRAZOL SOBRE O pH GÁSTRICO EM CÃES

    Directory of Open Access Journals (Sweden)

    Silvio Abrahão

    1999-01-01

    Full Text Available O objetivo deste trabalho foi investigar o efeito da ranitidina e omeprazol sobre o pH gástrico em 24 cães adultos, machos, sem raça definida, distribuídos em 3 grupos: grupo A - controle, grupo B - ranitidina e grupo C - omeprazol. O pH gástrico foi medido, após coleta do suco gástrico, com seringa, em cães submetidos a gastrotomia. Esta medida foi feita no grupo controle nos tempos zero, 30, 60, 90 e 120 minutos, no grupo ranitidina a medida foi feita no tempo zero, seguida de aplicação de 0,85 mg/kg de ranitidina por via endovenosa, sendo realizada nova medida nos tempos 30, 60, 90 e 120 minutos e, no grupo omeprazol a medida foi feita no tempo zero, seguida de aplicação de 0,68 mg/kg de omeprazol por via endovenosa, sendo realizada nova medida nos tempos 30,60, 90 e 120 minutos. A comparação entre os grupos mostrou um aumento significante do pH gástrico após o uso de ranitidina e omeprazol. Entretanto, os efeitos comparados da ranitidina e omeprazol não apresentaram diferenças significantes na variação do pH.The aim of this work was the ranitidine and omeprazole gastric pH effect investigation. 24 adults, male, mongrel dogs were distributed in 3 groups: group A - control, group B - ranitidine and group C - omeprazole. Gastric pH was measured after gastric juice syringe collection in dogs submitted to gastrotomy. Control group measurements were done at times zero, 30, 60, 90 and 120 minutes. Ranitidine group measurements were done at time zero, followed by 0,85 mg/kg endovenous ranitidine, and also at times 30, 60, 90 and 120 minutes. Omeprazole group measurements were done at time zero, followed by 0,68 mg/kg endovenous omeprazole and also at times 30, 60, 90 and 120 minutes. A significant increase in gastric pH, was observed, comparing groups, after ranitidine and omeprazole use. However, ranitidine and omeprazole compared effects presented no significant differences in pH variation.

  9. Influência da monofenilbutazona associada ou não ao omeprazol sobre o sistema digestório e renal de pôneis hígidos Influence of mofebutazone associated or not to omeprazole on the digestive and renal tracts of healthy ponies

    Directory of Open Access Journals (Sweden)

    José de Oliveira Pinto

    2009-02-01

    Full Text Available Os objetivos deste trabalho foram averiguar se a monofenilbutazona causa efeitos colaterais no trato digestório e lesões renais em pôneis hígidos e verificar a capacidade do omeprazol em inibir a gênese de úlceras gástricas. O experimento foi executado em duas etapas. Na primeira foram utilizados seis pôneis, sendo três deles tratados diariamente por via intravenosa (IV com as doses de 3, 4,5 ou 6mg kg-1 de monofenilbutazona durante 12 dias. Os demais, além de antiinflamatório, também receberam 3mg kg-1 de omeprazol. Já na segunda etapa foram incluídos quatro pôneis hígidos, sendo dois tratados com doses diárias de 4,5mg kg-1 de monofenilbutazona durante 12 dias e os demais com 5mL de NaCl a 0,9%, por via IV. Todos os pôneis foram submetidos à gastroscopia antes e após cada etapa experimental. Adicionalmente, na primeira etapa, foram realizadas urinálise e determinação dos valores de variáveis hematológicas (hematócrito e proteína plasmática total e bioquímicas (creatinina, albumina, Ca+2 e P+3. Na primeira etapa, apenas os dois pôneis tratados com 6mg kg-1 de monofenilbutazona apresentaram úlceras na região aglandular, ao longo da margo plicatus. Na segunda etapa, dois animais também apresentaram úlceras gástricas, sendo que um deles havia recebido apenas NaCl a 0,9%. A ocorrência das úlceras não foi influenciada (P>0,05 pela administração e pela dose da monofenilbutazona, nem pela presença do omeprazol. O efeito da monofenilbutazona sobre as variáveis hematológicas e bioquímicas foi inexpressivo (P+3 ou ausente (hematócrito, proteína plasmática total, creatinina, albumina, Ca+2 (P>0,05. Os resultados obtidos permitem concluir que: a ocorrência de úlceras na região aglandular de pôneis hígidos não sofre a influência da aplicação e da dose de monofenilbutazona, quando administrada durante 12 dias; úlceras em grau 4 na região aglandular de pôneis não necessariamente estão acompanhadas

  10. Possible drug-drug interaction between high-dose esomeprazole and phenprocoumon.

    Science.gov (United States)

    Becker, M L; Franken, W P J; Karapinar, F; Verzijl-Zeegers, R; Schalekamp, T; van der Hoeven, R T M

    2015-12-01

    It is established that omeprazole increases (R)+ warfarin levels with around 10 %. Whether (es)omeprazole also increase the plasma levels of acenocoumarol or phenprocoumon is still uncertain. We analyzed whether addition of (es)omeprazole to acenocoumarol or phenprocoumon increases the international normalized ratio (INR) levels and the risk of overanticoagulation. We analyzed all hospital admissions in four teaching hospitals. Patients who used coumarins and pantoprazole or (es)omeprazole simultaneously for at least four consecutive days were included in the study. We analyzed the highest INR level and whether patients had an INR level above six. We compared patients using omeprazole or esomeprazole with patients using pantoprazole, because for pantoprazole, no interaction has been reported. We analyzed 5747 admissions with 4540 patients using one of the drug combinations. For acenocoumarol (4578 admissions), no significant differences were found between users of esomeprazole, omeprazole, and pantoprazole. For phenprocoumon (1169 admissions), the highest INR measured was significantly higher in users of esomeprazole than in users of pantoprazole (4.7 versus 4.3; p = 0.035). No significant difference was found with omeprazole versus pantoprazole (4.3 versus 4.3; p = 0.66). A non-significant association was found between the esomeprazole dose and the highest INR level (p = 0.055). The risk of an INR above six did not differ significantly between esomeprazole and pantoprazole (27.7 % versus 22.9 %; p = 0.34). The use of esomeprazole simultaneously with phenprocoumon during hospital admissions might increase the anticoagulant effect. The clinical relevance seems to be limited, because no statistically significant increased risk of overanticoagulation was found.

  11. Propofol Infusion Syndrome in Adults: A Clinical Update

    Directory of Open Access Journals (Sweden)

    Aibek E. Mirrakhimov

    2015-01-01

    Full Text Available Propofol infusion syndrome is a rare but extremely dangerous complication of propofol administration. Certain risk factors for the development of propofol infusion syndrome are described, such as appropriate propofol doses and durations of administration, carbohydrate depletion, severe illness, and concomitant administration of catecholamines and glucocorticosteroids. The pathophysiology of this condition includes impairment of mitochondrial beta-oxidation of fatty acids, disruption of the electron transport chain, and blockage of beta-adrenoreceptors and cardiac calcium channels. The disease commonly presents as an otherwise unexplained high anion gap metabolic acidosis, rhabdomyolysis, hyperkalemia, acute kidney injury, elevated liver enzymes, and cardiac dysfunction. Management of overt propofol infusion syndrome requires immediate discontinuation of propofol infusion and supportive management, including hemodialysis, hemodynamic support, and extracorporeal membrane oxygenation in refractory cases. However, we must emphasize that given the high mortality of propofol infusion syndrome, the best management is prevention. Clinicians should consider alternative sedative regimes to prolonged propofol infusions and remain within recommended maximal dose limits.

  12. The Effect of Omeprazole Usage on the Viability of Random Pattern Skin Flaps in Rats.

    Science.gov (United States)

    Şen, Hilmi; Oruç, Melike; Işik, Veysel Murat; Sadiç, Murat; Sayar, Hamide; Çitil, Rana; Korkmaz, Meliha; Koçer, Uğur

    2017-06-01

    Necrosis of random pattern flaps caused by inadequate blood flow, especially in the distal part of the flap is one of the biggest challenges in reconstructive surgery. Various agents have been used to prevent flap ischemia. In this study, we used omeprazole, which is a potent inhibitor of gastric acidity to increase flap viability. In this study, 35 Wistar-Albino type rats which were divided into 5 equal groups were used. Random-pattern dorsal skin flaps were raised in all groups at seventh day of the study. Group 1 was accepted as control group, and the rats in this group was only given distilled water intraperitoneally for 14 days. Group 2 and group 3 received 10 and 40 mg/kg omeprazole daily for 14 days, respectively. Group 4 and group 5 were given distilled water for the first 7 days and then after the operations they received 10 and 40 mg/kg omeprazole daily for 7 days, respectively. Survival rates of the flaps were examined seventh day after elevation of the flaps by digital imaging and scintigraphy. After assessment of the amount of necrosis, number of vascular structures were counted histopathologically. Percentage of flap necrosis was found to be less in all omeprazole received groups. On digital imaging, percentages of flap necrosis in the study groups were statistically significantly lower than that of the control group (P 0.05).In the histopathologic specimens, it was detected that the mean number of vessels in proximal (a) and distal (c) portions of the flap in the study groups showed a significant increase when compared with the control group (P < 0.01 for groups 2, 4 and 5, and P < 0.05 for group 3). In conclusion, possible clinical usage of medications increasing gastrin during flap surgeries can be thought as a positive contributor. In this sense, this study showed that parenteral administration of omeprazole in skin flap surgery increases flap viability possibly by increasing gastrin levels.

  13. Effects of ischemia and omeprazole preconditioning on functional recovery of isolated rat heart

    Directory of Open Access Journals (Sweden)

    Nevena Jeremic

    2015-04-01

    Full Text Available AbstractObjective:The aim of this study was to compare protective effects of ischemic and potential protective effects of pharmacological preconditioning with omeprazole on isolated rat heart subjected to ischemia/reperfusion.Methods:The hearts of male Wistar albino rats were excised and perfused on a Langendorff apparatus. In control group (CG after stabilization period, hearts were subjected to global ischemia (perfusion was totally stopped for 20 minutes and 30 minutes of reperfusion. Hearts of group II (IPC were submitted to ischemic preconditioning lasting 5 minutes before 20 minutes of ischemia and 30 minutes of reperfusion. In third group (OPC hearts first underwent preconditioning lasting 5 minutes with 100μM omeprazole, and then submitted 20 minutes of ischemia and 30 minutes of reperfusion.Results:Administration of omeprazole before ischemia induction had protective effect on myocardium function recovery especially regarding to values of systolic left ventricular pressure and dp/dt max. Also our findings are that values of coronary flow did not change between OPC and IPC groups in last point of reperfusion.Conclusion:Based on our results it seems that ischemic preconditioning could be used as first window of protection after ischemic injury especially because all investigated parameters showed continuous trend of recovery of myocardial function. On the other hand, preconditioning with omeprazole induced sudden trend of recovery with positive myocardium protection, although less effective than results obtained with ischemic preconditioning not withstand, we must consider that omeprazole may be used in many clinical circumstances where direct coronary clamping for ischemic preconditioning is not possible.

  14. Studies of irradiation sterilization for single infusion device

    International Nuclear Information System (INIS)

    Chen Ruyan; Wang Keqin; Lu Zongmeng; Xiao Fenyuan; Xie Meizhi

    1988-05-01

    In practice of irradiation sterilization for single infusion device, object bacteria were selected and then their radiosensitivity were tested on the basis of practical production and irradiation environment. In view of the cylinder source and the static irradiation form, the dose rate of irradiation field and the dose distribution and uniformity in product box were measured in order to control sterilization quality. Through the measurements of material properties for irradiated infusion device and the test of causing rabbit fever as well as the survey of clinical practice, it was verified that the irradiation apparatus, the irradiation process and the product material etc. can satisfy the demands of sterilixzation and praction

  15. A cost-Utility Analysis Comparing Omeprazole with Ranitidine in the Maintenance Therapy of Peptic Esophageal Stricture

    Directory of Open Access Journals (Sweden)

    Jeffrey M Stal

    1998-01-01

    Full Text Available BACKGROUND: Recent studies have suggested that patients receiving omeprazole for prophylaxis against peptic esophageal stricture recurrence have less dysphagia and require fewer repeat dilations than patients receiving ranitidine.

  16. Infusion's greenfield subsidiary in Poland

    NARCIS (Netherlands)

    Williams, C.; van Eerde, W.; The, D.

    2012-01-01

    The president of Infusion Development Corporation was reviewing the progress of the new subsidiary the company had set up 15 months earlier in Krakow, Poland. The purpose of the subsidiary was to work with other Infusion offices around the world to provide innovative software development services to

  17. Developmental pharmacogenetics of CYP2C19 in neonates and young infants: omeprazole as a probe drug.

    Science.gov (United States)

    Zhao, Wei; Leroux, Stéphanie; Biran, Valérie; Jacqz-Aigrain, Evelyne

    2018-05-01

    Although substantial progress has been made in understanding of ontogeny of drug metabolism, there is still a gap of knowledge in developmental pharmacogenetics in neonates. We hypothesized that both age and pharmacogenetics might explain the developmental pattern of CYP2C19. We conducted a population pharmacokinetic-pharmacogenetic study to quantify the developmental pharmacogenetics of CYP2C19 in neonates and young infants using omeprazole as a probe drug. Pharmacokinetic samples were collected from 51 Caucasian neonates and young infants, who were receiving omeprazole treatment. Population pharmacokinetic-pharmacogenetic analysis of omeprazole and its metabolites was performed using NONMEM. Data fitted a one-compartment parent and metabolite model with first-order absorption and elimination. CYP2C19 and CYP3A4 are predominantly involved in the metabolism of omeprazole despite their relatively low activities compared to adults. The clearance of omeprazole converted to 5-hydroxy-omeprazole (CL OMZ-M1 ) increases with postnatal age. In CYP2C19 poor and intermediate metabolizers, model-predicted CL OMZ-M1 are 12.5% (5-95% percentile: 3-14.9%) and 44.9% (5-95% percentile: 29.9-72.6%) of the value in extensive/ultrarapid metabolizer, respectively. Model-predicted absorption rate constant of omeprazole is 6.93 (5-95% percentile: 3.01-14.61) times higher in ABCB1 homozygous mutant patients, 1.86 (5-95% percentile: 0.86-3.47) times higher in ABCB1 heterozygous patients than that in ABCB1 homozygous wild-type patients. Developmental pharmacogenetics of CYP2C19 was quantitatively described in neonates and young infants using omeprazole as a probe drug. Our findings emphasize the importance of semiphysiological developmental pharmacokinetic modelling approach when evaluating developmental pharmacogenetics of drugs with multiple routes of biotransformation. © 2018 The British Pharmacological Society.

  18. Therapy with omeprazole modulates regulatory T cell/T helper 17 immune response in children with duodenal ulcers.

    Science.gov (United States)

    Li, Chuan-Ying; Wu, Cheng

    2018-04-01

    The purpose of this study was to determine the effect of omeprazole on the regulatory T cell (Treg) and T helper 17 (Th17)-mediated response in patients with duodenal ulcers (DUs). DU patients were randomly divided into omeprazole and colloid bismuth subcitrate treatment groups. The ratios of Th17 and Treg in peripheral blood mononuclear cells (PBMCs) were measured. Cytokine production and Foxp3 + - and RORγt-positive cells were detected. The expressions of STAT3, p-STAT3, STAT5 and p-STAT5 were detected by Western blot. The results showed that DU patients had an imbalanced Treg/Th17 response, as reflected by the higher IL-17 level and Th17 ratio and lower IL-10 level and Treg proportion in serum compared with those in the healthy volunteers. The administration of omeprazole to the patients significantly increased Treg and IL-10 levels and reduced Th17 and IL-17 levels. Omeprazole markedly increased the number of Foxp3-positive cells, decreased the number of RORγt-positive cells and restored the balanced ratio of IL-10/IL-17 in the ulcer tissue. Interestingly, we observed a negative correlation between the ratios of Treg/Th17 and the pathological scores in damaged tissues. Of note, H. pylori-infected PBMCs showed decreased Treg and an increased Th17 proportion, which could be reversed by omeprazole. Finally, omeprazole increased the expression of p-STAT5 and reduced the level of p-STAT3 without any effects on the total expression of STAT5 and STAT3. Our data suggest that omeprazole treatment restores the equilibrium of the Treg/Th17-mediated response in DU patients. Moreover, the modulation of p-STAT3 and p-STAT5 expression by omeprazole induced balanced polarisation of Treg/Th17.

  19. A Phase I, open-label, randomized, crossover study in three parallel groups to evaluate the effect of Rifampicin, Ketoconazole, and Omeprazole on the pharmacokinetics of THC/CBD oromucosal spray in healthy volunteers.

    Science.gov (United States)

    Stott, Colin; White, Linda; Wright, Stephen; Wilbraham, Darren; Guy, Geoffrey

    2013-12-01

    This Phase I study aimed to assess the potential drug-drug interactions (pharmacokinetic [PK] and safety profile) of Δ9-tetrahydrocannabinol (THC)/cannabidiol (CBD) oromucosal spray (Sativex (®), nabiximols) in combination with cytochrome P450 (CYP450) inducer (rifampicin) or inhibitors (ketoconazole or omeprazole). Thirty-six healthy male subjects were divided into three groups of 12, and then randomized to one of two treatment sequences per group. Subjects received four sprays of THC/CBD (10.8/10 mg) alongside single doses of the CYP3A and 2C19 inducer rifampicin (600 mg), CYP3A inhibitor ketoconazole (400 mg) or CYP2C19 inhibitor omeprazole (40 mg). Plasma samples were analyzed for CBD, THC and its metabolite 11-hydroxy-THC (11-OH-THC). A single dose of four sprays of THC/CBD spray (10.8/10 mg) following repeated doses of rifampicin (600 mg) reduced the Cmax and AUC of all analytes. Cmax reduced from 2.94 to 1.88 ng/mL (-36%), 1.03 to 0.50 ng/mL (-52%) and 3.38 to 0.45 ng/mL (-87%) for THC, CBD and 11-OH-THC, respectively compared to single dose administration of THC/CBD spray alone. Ketoconazole co-administration with THC/CBD spray had the opposite effect, increasing the Cmax of the respective analytes from 2.65 to 3.36 ng/mL (+27%), 0.66 to 1.25 ng/mL (+89%) and 3.59 to 10.92 ng/mL (+204%). No significant deviations in Cmax or AUC for any analyte were observed when THC/CBD spray was co-administered with omeprazole. THC/CBD spray was well tolerated by the study subjects both alone and in combination with rifampicin, ketoconazole and omeprazole. Evaluation of the PKs of THC/CBD spray alone and in combination with CYP450 inhibitors/inducers suggests that all analytes are substrates for the isoenzyme CYP3A4, but not CYP2C19. On the basis of our findings, there is likely to be little impact on other drugs metabolized by CYP enzymes on the PK parameters of THC/CBD spray, but potential effects should be taken into consideration when co-administering THC/CBD spray

  20. The effect of short-term oral treatment with omeprazole or pantoprazole on the function of polymorphonuclear neutrophils.

    Science.gov (United States)

    Kostrzewska, Maja; Garley, Marzena; Ratajczak-Wrona, Wioletta; Jabłońska, Ewa; Jamiołkowski, Jacek; Dabrowski, Andrzej

    2017-06-01

    Recent studies report an increased risk of enteric infections in patients treated with proton pump inhibitors (PPIs). Polymorphonuclear neutrophils (PMNs) play a key role in host response to bacterial infection. We evaluated the effect of omeprazole and pantoprazole treatment on the PMN function. Fifteen patients were treated with omeprazole 20 mg daily and 15 patients with pantoprazole 40 mg daily for 7 days. Treatment with omeprazole or pantoprazole had no effect on spontaneous nitroblue tetrazolium (NBT) test results. Significant increase in the percentage of phagocytes in the omeprazole group in stimulated NBT test (by 69%) was found. Treatment with omeprazole or pantoprazole had no effect on nitric oxide (NO) concentration in the PMN culture supernatant and serum, cyclic guanosine monophosphate concentration in the PMN culture supernatant and serum, as well as inducible nitric oxide synthase (iNOS) protein expression and p38 mitogen-activated protein kinase activity in PMNs. In conclusion, treatment with PPI has no effect on NO production and p38 mitogen-activated protein kinase activity in PMNs. Interestingly, short-term treatment with omeprazole but not with pantoprazole enhances PMN reactive oxygen species production.

  1. Rationale and design of Apo-I Event Reduction in Ischemic Syndromes I (AEGIS-I): A phase 2b, randomized, placebo-controlled, dose-ranging trial to investigate the safety and tolerability of CSL112, a reconstituted, infusible, human apoA-I, after acute myocardial infarction.

    Science.gov (United States)

    Gibson, C Michael; Korjian, Serge; Tricoci, Pierluigi; Daaboul, Yazan; Alexander, John H; Steg, Philippe G; Lincoff, A Michael; Kastelein, John J P; Mehran, Roxana; D'Andrea, Denise; Merkely, Bela; Zarebinski, Maciej; Ophius, Ton Oude; Harrington, Robert A

    2016-10-01

    Despite aggressive pharmacotherapy and stenting, there is a residual risk of major adverse cardiovascular events among patients with acute coronary syndrome. High-density lipoprotein (HDL) has been a major target for secondary acute coronary syndrome prevention; however, a better understanding of the physiologic function of HDL has demonstrated that a high cholesterol efflux capacity, rather than high HDL concentrations alone, may be critical to improving outcomes. CSL112, a reconstituted, infusible human apolipoprotein A-I, has been demonstrated to increase cholesterol efflux capacity and to have a protective effect in experimental models of atherosclerotic cardiovascular disease. The AEGIS-I trial (ClinicalTrials.govNCT02108262) is a phase 2b, multicenter, randomized, placebo-controlled, dose-ranging clinical trial to evaluate the hepatic and renal safety of multiple administrations of 2 doses of CSL112 among subjects with acute myocardial infarction (AMI). Approximately 1,200 subjects (400 per treatment group) with either normal renal function or mild renal impairment will be enrolled up to 7 days after an AMI and will be stratified by renal function and randomized in a 1:1:1 ratio to either 1 of 2 doses of CSL112 (either 2 g or 6 g) or placebo as a weekly 2-hour infusion over the course of 4 consecutive weeks. The coprimary safety endpoints will be the incidence of hepatic and renal toxicity, defined as either confirmed ALT >3 × ULN, total bilirubin >2 × ULN, serum creatinine ≥1.5×baseline value, or a new requirement for renal replacement therapy through the end of the active treatment period. The AEGIS-I trial will characterize the safety profile of CSL112, a reconstituted formulation of apolipoprotein A-I, and will assess if administration to patients with a recent AMI is associated with a clinically significant alteration in either liver or kidney function when compared with placebo. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Long-term BPA infusions. Evaluation in the rat brain tumor and rat spinal cord models

    International Nuclear Information System (INIS)

    Coderre, J.A.; Micca, P.L.; Nawrocky, M.M.; Joel, D.D.; Morris, G.M.

    2000-01-01

    In the BPA-based dose escalation clinical trial, the observations of tumor recurrence in areas of extremely high calculated tumor doses suggest that the BPA distribution is non-uniform. Longer (6-hour) i.v. infusions of BPA are evaluated in the rat brain tumor and spinal cord models to address the questions of whether long-term infusions are more effective against the tumor and whether long-term infusions are detrimental in the central nervous system. In the rat spinal cord, the 50% effective doses (ED 50 ) for myeloparesis were not significantly different after a single i.p. injection of BPA-fructose or a 6 hour i.v. infusion. In the rat 9L gliosarcoma brain tumor model, BNCT following 2-hr or 6-hr infusions of BPA-F produced similar levels of long term survival. (author)

  3. Radioprotection of the digestive tract by intravenous infusion of vasopressin

    Energy Technology Data Exchange (ETDEWEB)

    Juillard, G.J.F.; Peter, H.H.; Weisenburger, T.H.; Tesler, A.S.; Langdon, E.A.; Barenfus, M.; Lagasse, L.D.; Watring, W.E.; Smith, M.L.

    1975-09-01

    The effect of venous infusions of vasopressin during fractionated abdominal radiation exposures was evaluated in four pairs of dogs. In each pair, the control dog was given venous infusion of saline during irradiation. The results were analyzed from clinical observation, autopsy findings, and pathological examination. It appears that venous infusion of vasopressin has a definite and reproducible effect of radioprotection on the gastrointestinal tract, the dose modifying factor (DMF) being 1.5. Radiation therapy of the gynecologic malignancies would be one major application since the radiosensitivity of the intestinal tract is often a limiting factor in delivering high doses to the tumor, and further investigations are being done to study the effects of vasopressin on the radiosensitivity of malignant tumors.

  4. Efficacy of omeprazole, famotidine, mosapride and teprenone in patients with upper gastrointestinal symptoms: an omeprazole-controlled randomized study (J-FOCUS

    Directory of Open Access Journals (Sweden)

    Sakurai Kouichi

    2012-05-01

    Full Text Available Abstract Background In Japan, treatment guidelines are lacking for patients with upper gastrointestinal symptoms. We aimed to compare the efficacy of different drugs for the treatment of uninvestigated upper gastrointestinal symptoms. Methods This was a randomized, open-label, parallel-group multicenter study. Helicobacter pylori-negative, endoscopically uninvestigated patients ≥ 20 years of age with upper gastrointestinal symptoms of at least moderate severity (Global Overall Symptom score [GOS] ≥ 4 on a 7-point Likert scale were randomized to treatment with omeprazole (10 mg once daily, famotidine (10 mg twice daily, mosapride (5 mg three times daily or teprenone (50 mg three times daily. The primary endpoint was sufficient relief of upper gastrointestinal symptoms after 4 weeks of treatment (GOS ≤ 2. UMIN clinical trial registration number: UMIN000005399. Results Of 471 randomized patients, 454 were included in the full analysis set. After 4 weeks of treatment, sufficient symptom relief was achieved by 66.9% of patients in the omeprazole group, compared with 41.0%, 36.3% and 32.3% in the famotidine, mosapride and teprenone groups, respectively (all, p  Conclusions The favorable efficacy and safety profiles of omeprazole in relieving uninvestigated upper gastrointestinal symptoms support its use as first-line treatment in this patient group in Japan. Patients who show no improvement in symptoms despite PPI use, and those with alarm symptoms (such as vomiting, GI bleeding or acute weight loss should receive further investigation, including prompt referral for endoscopy. Trial registration UMIN000005399.

  5. Evaluation of antiulcer activity of indole-3-carbinol and/or omeprazole on aspirin-induced gastric ulcer in rats.

    Science.gov (United States)

    El-Shinnawy, Nashwa A; Abd-Elmageid, Samira A; Alshailabi, Eda M A

    2014-05-01

    The present work is an attempt to elucidate the antiulcer activity of indole-3-carbinol (I3C), which is one of the anticarcinogenic phytochemicals found in the vegetables of Cruciferae family such as broccoli and cauliflower, alone or in combination with omeprazole (OMP), a proton pump inhibitor, to diminish the effects of induced acute gastric ulcer by aspirin (ASA) in male albino rats. A total of 48 adult male albino rats were used in the present study. Animals were divided into eight experimental groups (six animals each group). They were given different experimental inductions of ASA at a dose of 500 mg/kg/body weight, OMP at a dose of 20 mg/kg/body weight and I3C at a dose of 20 mg/kg/body weight either alone or in combination with each other orally for a duration of 7 days. Inner stomach features, ulcer index, pH activity, body weight, stomach weight, hematological investigations, serum total protein albumin and reduced glutathione activity were investigated in addition to the histological, histochemical and immunohistochemical stain of cyclooxygenase-2 to the stomach tissue of normal control, ulcerated and treated ulcerated rats. The results of this study revealed that oral administration of ASA to rats produced the expected characteristic mucosal lesions. OMP accelerated ulcer healing but the administration of I3C either alone or in combination with OMP to ASA-ulcerated rats produced a profound protection to the gastric mucosa from injury induced by ASA. Our results suggested that administration of antiulcer natural substances such as I3C in combination with the perused treatment such as OMP is a very important initiative in the development of new strategies in ulcer healing.

  6. Lipolytic response to glucose infusion in human subjects

    International Nuclear Information System (INIS)

    Wolfe, R.R.; Peters, E.J.

    1987-01-01

    The authors have determined the effect of various rates of glucose infusion on the rates of release of glycerol (R/sub a/ glycerol), free fatty acids (R/sub a/ FFA), and on energy metabolism in normal human volunteers. Plasma kinetics were determined with use of the stable isotopic tracers D-5-glycerol and [1- 13 C]palmitate, and energy metabolism was determined by indirect calorimetry. The effect of glucose infusion on R/sub a/ glycerol and R/sub a/ FFA was dose-dependent. At 4 mg x kg -1 x min -1 , both R/sub a/ glycerol and R/sub a/ FFA were suppressed; at 8 mg x kg -1 x min -1 , R/sub a/ FFA was even more depressed, but R/sub a/ glycerol was similar to the value during the 4 mg x kg -1 x min -1 infusion. At all infusion rates tested, the amount of potential energy available from the sum of the glucose infusion and endogenously mobilized fat was always greater than when no glucose was infused. Glucose decreased fat mobilization by both inhibiting lipolysis and stimulating reesterification, thus causing a significant increase in triglyceride-fatty acid substrate cycling within the adipose tissue. Plasma insulin was determined by radioimmunoassay

  7. Effects of omeprazole and cisapride treatment in Japanese asthmatics with reflux esophagitis

    Directory of Open Access Journals (Sweden)

    Katsuya Fujimori

    1997-01-01

    Full Text Available In the United States and Europe, gastroesophageal reflux (GER is receiving attention as a potential cause of bronchial asthma. Few Japanese case reports have described this relationship. Therefore, we investigated the effect of omeprazole and cisapride on pulmonary function tests, blood gases and home peak expiratory flow rates (PEFR in six Japanese outpatients with asthma and proven GER. After 8 weeks of treatment, reflux esophagitis had improved in all patients. However, the parameters of pulmonary function showed no change other than a significant post- treatment increase in home PEFR (4.4-27.7% in three patients. These results suggest that anti-reflux (omeprazole and cisapride treatment will produce small improvements in the PEFR in some Japanese asthmatics with GER.

  8. Continuous propofol infusion in 142 critically ill children.

    Science.gov (United States)

    Cornfield, David N; Tegtmeyer, Ken; Nelson, Michael D; Milla, Carlos E; Sweeney, Michael

    2002-12-01

    In recent years, continuous intravenous propofol infusion has been widely used in pediatric intensive care units. Several case reports have raised concerns about its safety. The objective of this study was to report our experience with continuous intravenous propofol in consecutive patients during an 18-month period. The study design was a retrospective review of a case series. Case was defined as a critically ill child who was treated with continuous intravenous propofol. The attending physician staff agreed to prescribe propofol via continuous intravenous infusion at a dose not to exceed 50 microg/kg/min. The protocol allowed for each patient to receive an additional intravenous bolus of propofol at a dose of 1 mg/kg no more than once per hour. The study entailed data collection from consecutive patients who were prescribed a continuous infusion of propofol in either the pediatric intensive care unit or bone marrow transplant unit. Data from 142 patients were analyzed. Each patient enrolled was adequately sedated. Administration of propofol via continuous intravenous infusion was not associated with metabolic acidosis or hemodynamic compromise. No patient in the study group was inadvertently extubated or had a central venous catheter accidentally discontinued. Propofol can be safely and effectively used to provide sedation to critically ill infants and children. We speculate that continuous infusion of propofol for extended periods of time should not exceed 67 microg/kg/min.

  9. Single enantiomer versus racemate: chiral distinction in the proton pump inhibitors omeprazole and esomeprazole.

    Science.gov (United States)

    Marom, Hili; Pogodin, Sergey; Agranat, Israel

    2014-04-01

    Chiral distinction in the proton pump inhibitor drugs omeprazole and in its chiral-switch esomeprazole magnesium was studied employing the Density Functional Theory (DFT) method. At B3LYP/6-311G(d,p), the 6-methoxy∙∙∙6-methoxy and 5-methoxy∙∙∙5-methoxy homochiral and heterochiral dimers were calculated. The chiral distinction free energies (ΔΔG(298,(RS-SS))) between the cyclic C2-(S,S)- and Ci-(R,S)-dimers with two intermolecular hydrogen bonds are 3.8, 1.9 (with BSSE counterpoise correction), and -6.9 (with D3 dispersion and BSSE counterpoise corrections) kJ/mol. Adding water as an implicit solvent (polarized continuum model [PCM] model) resulted in a chiral distinction energy of -3.3 kJ/mol, indicating a reversal of the order of the relative stabilities of C2-(S,S)- and Ci-(R,S)-dimers. The chiral distinction free energies between the corresponding (less stable) C1-dimers with one intermolecular hydrogen bond are -9.3, -5.8 (with BSSE CC), 17.6 (D3 + BSSE CC), and -3.2 (H2O) kJ/mol. The results highlight the contention that omeprazole is not just a superposition of its enantiomer constituents. They are consistent with the pharmacological evidence of enantiomer-enantiomer interactions in omeprazole versus esomeprazole and the differences between the drugs omeprazole and esomeprazole magnesium and support the lodged application for regulatory supplementary protection certificate (SPC) exclusivity for the esomeprazole-related combination drug Vimovo. Copyright © 2014 Wiley Periodicals, Inc.

  10. Development and evaluation of omeprazole pellets fabricated by sieving-spheronization and extrusion - spheronization process.

    Science.gov (United States)

    Karim, Sabiha; Baie, Saringat H; Hay, Yuen Kah; Bukhari, Nadeem Irfan

    2014-05-01

    Pelletized dosage forms can be prepared by different methods which, in general, are time consuming and labor intensive. The current study was carried out to investigate the feasibility of preparing the spherical pellets of omeprazole by sieving-spheronization. An optimized formulation was also prepared by extrusion-spheronization process to compare the physical parameters between these two methods. The omeprazole pellets were consisted of microcrystalline cellulose, polyvinylpyrrolidone K 30, sodium lauryl sulphate and polyethylene glycol 6000. The omeprazole delay release system was developed by coating the prepared pellets with aqueous dispersion of Kollicoat 30 DP. The moisture content, spheronization speed and residence time found to influence the final properties of omeprazole pellets prepared by extrusion-spheronization and sieving-spheronization. The Mann-Whitney test revealed that both methods produced closely similar characteristics of the pellets in terms of, friability (p=0.553), flowability (p=0.677), hardness (p=0.103) and density (bulk, p=0.514, tapped, p=0.149) except particle size distribution (p=0.004). The percent drug release from the coated formulation prepared by sieving-spheronization and extrusion spheronization was observed to be 84.12 ± 1.10% and 82.67 ± 0.96%, respectively. Dissolution profiles of both formulations were similar as indicated by values of f1 and f2, 1.52 and 89.38, respectively. The coated formulation prepared by sieving-spheronization and commercial reference product, Zimore ® also showed similar dissolution profiles (f1=1.22, f2=91.52). The pellets could be prepared using sieving-spheronization. The process is simple, easy, less time- and labor-consuming and economical as compared to extrusion-spheronization process.

  11. Treatment of hemorrhagic gastritis by Ankaferd blood stopper versus Omeprazole: experimental randomized rat models.

    Science.gov (United States)

    Batgi, Hikmetullah; Akbal, Erdem; Koçak, Erdem; Akyürek, Ömer; Köklü, Seyfettin; Dönmez, Melahat; Güneş, Fahri

    2016-12-01

    Ankaferd blood stopper (ABS) is a herbal extract that enhances mucosal healing. It has therapeutic potential in the management of external hemorrhage and controlling gastrointestinal bleeding associated with various benign lesions refractory to conventional antihemorrhagic measures. The aim of this experimental study was to assess the effects of ABS on hemorrhagic lesions and compare them with omeprazole. The study was conducted on 30 rats. Rats were divided into five groups: group A (only indomethacin), group B (ABS administration 60 min before indomethacin-induced injury), group C (ABS administration 30 min after indomethacin-induced injury), group D (omeprazole administration 60 min before indomethacin-induced injury), group E (omeprazole administration 30 min after indomethacin-induced injury). Gastric mucosal lesions were produced by indomethacin in all three groups. The effect was studied morphologically 6 h after oral administration of the drug. Subsequently, affected tissue was examined histologically. Based on the number and the total size of hemorrhagic lesions, the hemorrhagic lesion scores were significantly better in Group C compared to other groups (p < 0.05). The hemorrhagic lesion score of Group B was significantly better than Group D and Group A (p < 0.05). Omeprazole groups (Group D, Group E) did not show significant improvement as indicated by macroscopic scores. There was no significant difference between the groups with respect to microscopic scores. These results indicate that ABS has a potent inhibitory action on indomethacin-induced gastric bleeding and mucosal lesions and it is useful in the treatment of acute gastric mucosal lesions.

  12. The effects of omeprazole on interdigestive motility and early postprandial levels of gastrin and secretin

    DEFF Research Database (Denmark)

    Rasmussen, L; Oster-Jørgensen, E; Qvist, N

    1992-01-01

    Ten healthy men participated in a crossover study, and the experiments took place after 10 days of treatment (40 mg omeprazole every morning). Blood samples were drawn at fixed intervals during a complete migrating motor complex (MMC) cycle. The manometric pressure tube was removed after passage ...... plasma gastrin, ii) a decrease in secretin in phases I and III, iii) an augmented meal-stimulated gastrin response, and iv) a secretin response characterized by a significantly lower mean in the immediate postprandial period....

  13. Comparison between tocotrienol and omeprazole on gastric growth factors in stress-exposed rats.

    Science.gov (United States)

    Nur Azlina, Mohd Fahami; Qodriyah, Hj Mohd Saad; Chua, Kien Hui; Kamisah, Yusof

    2017-08-28

    To investigate and compare the effects of tocotrienol and omeprazole on gastric growth factors in rats exposed to water-immersion restraint stress (WIRS). Twenty-eight male Wistar rats were randomly assigned to four groups of seven rats. The two control groups were administered vitamin-free palm oil (vehicle) and the two treatment groups were given omeprazole (20 mg/kg) or tocotrienol (60 mg/kg) by oral gavage. After 28 d of treatment, rats from one control group and both treated groups were subjected to WIRS one time for 3.5 h. Gastric lesions were measured and gastric tissues were obtained to measure vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), and transforming growth factor-alpha (TGF-α) mRNA expression. Rats exposed to WIRS for 3.5 h demonstrated the presence of considerable ulcers in the form of gastric erosion. The lesion index in the stressed control (S) group was increased ( P < 0.001) compared to the tocotrienol treated and omeprazole treated groups. Stress led to a decrease in gastric VEGF ( P < 0.001), bFGF ( P < 0.001) and TGF-α ( P < 0.001) mRNA levels and caused an increase in EGF mRNA ( P < 0.001) that was statistically significant compared to the non-stressed control group. Although both treatment agents exerted similar ulcer reducing ability, only treatment with tocotrienol led to increased expression of VEGF ( P = 0.008), bFGF ( P = 0.001) and TGF-α ( P = 0.002) mRNA. Tocotrienol provides gastroprotective effects in WIRS-induced ulcers. Compared to omeprazole, tocotrienol exerts a similar protective effect, albeit through multiple mechanisms of protection, particularly through up-regulation of growth factors that assist in repair of gastric tissue injuries.

  14. Instantaneous enteric nano-encapsulation of omeprazole: pharmaceutical and pharmacological evaluation.

    Science.gov (United States)

    Bendas, Ehab R; Abdelbary, Aly A

    2014-07-01

    Recently, great attention has been paid to nanocapsules. The interest of these structures is due to their promising applications as drug delivery systems. The objective of this study was to develop novel enteric coating technique based on instantaneous encapsulation of the acid-labile drug, omeprazole in innovative enteric nanocapsules. Omeprazole enteric nanocapsules were formulated by varying the type and amount of the enteric polymer. The particle size (PS), polydispersity index (PDI), zeta potential (ZP) and encapsulation efficiency (EE) values of the prepared enteric nanocapsules were determined. A full 2(1)×3(1) factorial design was used for planning and analysis of the experimental trials to select the optimized formulation. The highest desirability value was 0.7463 for formula E3 (containing 200mg hydroxypropyl methylcellulose phthalate (HPMCP)). The stability of omeprazole was reflected by the absence of the exothermal peak when the drug was encapsulated as detected by differential scanning calorimetry (DSC) thermograms. In vitro drug release study confirmed the USP specifications required to meet the key formulation characteristics of gastro-resistance. In vivo pharmacological assessment showed that the optimized nanocapsules were able to protect rat stomach against ulcer formation compared to the aqueous suspension of the drug which showed less significant protection. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. The effects of omeprazole on interdigestive motility and early postprandial levels of gastrin and secretin

    Energy Technology Data Exchange (ETDEWEB)

    Rasmussen, L.; Oester-Joergensen, E.; Qvist, N. (and others) (Rigshospitalet, Copenhagen (Denmark))

    1992-01-01

    10 healthy men participated in a crossover study, and the experiments took place after 10 days of treatment (40 mg omeprazole every morning). Blood samples were drawn at fixed intervals during a complete migrating motor complex cycle. The manometric pressure tube was removed after passage of the second duodenal phase III, and an omelet tagged with {sup 99m}Tc was ingested, followed by 150 ml of water tagged with {sup 111}In-diethylenetriaminepentaacetic acid. Mean plasma gastrin in phases I, II, and III in the omeprazole group was 18.8, 23.3, 19.9, respectively. The corresponding figures for the placebo group were 9.3, 9.6, 9.5, respectively. It is concluded that 40 mg omeprazole elicits a phase-related increase in fasting plasma gastrin, a decrease in secretin in phases I and III, an augmented meal-stimulated gastrin response, and a secretin response characterized by a significantly lower mean in the immediate postprandial period. 12 refs., 4 figs.

  16. The effects of omeprazole on interdigestive motility and early postprandial levels of gastrin and secretin

    International Nuclear Information System (INIS)

    Rasmussen, L.; Oester-Joergensen, E.; Qvist, N.

    1992-01-01

    10 healthy men participated in a crossover study, and the experiments took place after 10 days of treatment (40 mg omeprazole every morning). Blood samples were drawn at fixed intervals during a complete migrating motor complex cycle. The manometric pressure tube was removed after passage of the second duodenal phase III, and an omelet tagged with 99m Tc was ingested, followed by 150 ml of water tagged with 111 In-diethylenetriaminepentaacetic acid. Mean plasma gastrin in phases I, II, and III in the omeprazole group was 18.8, 23.3, 19.9, respectively. The corresponding figures for the placebo group were 9.3, 9.6, 9.5, respectively. It is concluded that 40 mg omeprazole elicits a phase-related increase in fasting plasma gastrin, a decrease in secretin in phases I and III, an augmented meal-stimulated gastrin response, and a secretin response characterized by a significantly lower mean in the immediate postprandial period. 12 refs., 4 figs

  17. Hypoglycaemia secondary to labetalol infusion.

    Science.gov (United States)

    Immanni, Sudhir; Khan, Ehtesham Izhar; Staunton, Michael

    2011-05-01

    A 42-year-old multigravida with severe pre-eclampsia had an emergency caesarean section under spinal anaesthesia. Peri-operatively, her arterial pressure was controlled with oral methyldopa and an intravenous infusion of labetalol. Postoperatively, in the Intensive Care Unit, she had recurrent episodes of hypoglycaemia which required treatment with intravenous glucose. These episodes resolved when the labetalol infusion was stopped. Clinicians should be aware of the potential of labetalol to cause hypoglycaemia.

  18. Acute Effects Of Oral Calcium Carbonate With And Without The Addition Of Omeprazole And Fiber Enriched Milk On Serum Calcium Concentrations In Postmenopausal Women

    Directory of Open Access Journals (Sweden)

    Paula Aragão Prazeres Oliveira

    2017-05-01

    Full Text Available Introduction: In recent years, some studies have shown an increase in cardiovascular risk due to the use of calcium supplements in excess of the recommended doses. One hypothesis is that some calcium supplements lead to a more pronounced elevation of serum calcium concentrations. Objectives: The aim of this study was to evaluate the serum calcium responses after ingestion of calcium carbonate, with and without the prior use of omeprazole, and after ingestion of soluble fiber enriched milk (SFM. Method: Five postmenopausal women were evaluated in three phases. For each phase, the serum calcium responses were determined at 0h (baseline, 1h, 2h, 3h and 4h. After ingestion of 1200mg of calcium, both for the patients who received the calcium carbonate and for those who received SFM. The rise in serum calcium observed after ingestion of calcium carbonate with a calcium peak of 0.56 mg/dl (p=0.032, and it was higher when compared to SFM 0.26 mg/dl (p=0.284. There was no significant elevation of serum calcium after ingestion of SFM. Results: The calcium responses were negative after the administration of omeprazole in comparison with the use of calcium carbonate and SFM, reaching 7.06mg/dl vs 9.04mg/dl vs 9.12mg/dl at 0h, 5.30mg/dl vs 9. 32mg/dl vs 9.00mg/dl at 1hr, 5.52mg/dl vs 9.48mg/dl vs 9.32mg/dl at 2hr, 5.18mg/dl vs 9.48mg/dl vs 9.34mg/dl at, respectively. In conclusion, our data show that the same amount of SFM induced a lower serum calcium response when compared to calcium carbonate. Conclusion: The use of omeprazole significantly reduced the intestinal absorption of calcium carbonate.

  19. A pharmacokinetic model of drug-drug interaction between clopidogrel and omeprazole at CYP2C19 in humans.

    Science.gov (United States)

    Tangamornsuksan, Wimonchat; Thiansupornpong, Pongpak; Morasuk, Thirawut; Lohitnavy, Ornrat; Lohitnavy, Manupat

    2017-07-01

    Clopidogrel is a thienopryridine antiplatelet agent commonly used in the management of cardiovascular diseases. Clopidogrel is metabolized by hepatic CYP2C19 and CYP2B6, therefore, co-administration of clopidogrel and CYP2C19 inhibitors can alter pharmacokinetics of clopidogrel. Omeprazole is a proton pump inhibitor used for decreasing gastric acid production. Omeprazole is known to be a potent inhibitor of CYP2C19. Thus when the drugs are simultaneously administered, clopidogrel plasma concentration levels can be increased. However, plasma levels of the active metabolite of clopidogrel can be significantly decreased, thereby, its antiplatelet activity is reduced. We aimed to develop a mathematical model describing a drug-drug interaction between clopidogrel and omeprazole in humans. Searching for pharmacokinetic interaction studies between clopidogrel and omeprazole in humans was performed in PubMed. Six studies were selected into our modeling purposes to develop 3 mathematical models (i.e. 4 studies for clopidogrel alone, 1 study for omeprazole alone and 1 study for clopidogrel-omeprazole interaction). Subsequently, concentration-time course data from the selected studies were extracted. Computer codes and simulations were performed using the Advanced Continuous Simulating Language Extreme (ACSLX) program. We successfully developed 3 mathematical models which are able to describe all of the datasets. Our clopidogrel-omeprazole pharmacokinetic interaction model with a description of competitive inhibition at CYP2C19 could successfully describe concentration-time courses from the selected datasets. Our interaction model may be useful in predicting plasma levels of clopidogrel and its active metabolite.

  20. Association between omeprazole use and Clostridium difficile infection among hospitalized patients: A case-control study of the Saudi population.

    Science.gov (United States)

    Al Otaibi, Hazza; Ahmed, Anwar E; Alammari, Maha

    2017-01-01

    Background: While few international studies have assessed the association between omeprazole use and the risk of Clostridium difficile infection (CDI), research into this is lacking in Saudi Arabia and the Middle East region. The aim of this study was to determine whether exposure to omeprazole is associated with the risk of Clostridium difficile infection in a sample of hospitalized Saudi patients. Methodology: A retrospective matched case-control study was conducted at the King Abdulaziz Medical City in Riyadh, Saudi Arabia, from 1 August 2010 through 31 July 2015. The analysis included a total of 200 patients: 100 CDI cases and 100 matched controls. Results: The majority (60%, 120 out of 200) of patients had received proton pump inhibitors (PPIs), and a minority (18.5%, 37 out of 200) had received omeprazole. The PPI use was insignificantly higher in CDI cases than in controls. However, the use of omeprazole was significantly higher in CDI cases compared with controls. Specifically, patients receiving omeprazole were two times more likely to develop CDI compared with controls (aOR = 2.1, 95% confidence interval (CI) = (1.007-4.437)). After adjusting for potential predictors of CDI, watery diarrhea (aOR = 59.1, 95% CI = 19.831-175.974) and abdominal pain (aOR = 7.5, 95% CI = 2.184-25.445) were found to be independent predictors of CDI. Conclusions: The data suggests that PPIs were commonly used in patients admitted to King Abdulaziz Medical City in Riyadh: six out of ten patients received PPIs. The findings support a possible association between the use of omeprazole and a high risk of CDI. To confirm causality, the link between omeprazole and CDI should be assessed in a large interventional study.

  1. An experimental study on renal arterial and parenchymal change caused by selective renal infusion of epinephrine

    International Nuclear Information System (INIS)

    Jeon, Seok Chol; Yeon, Kyung Mo; Han, Man Chung

    1981-01-01

    Selective infusion of the epinephrine into the renal artery has been used in the field of the diagnostic and the therapeutic radiology for correct diagnosis and effective treatment, respectively. However, administration of overdose of epinephrine may cause serious complication, renal infarction. The study was undertaken to evaluate the sequential change of renal arterial constrictive effect of selective infusion of epinephrine into renal artery and to determine the critical doses of epinephrine producing irreversible renal infarct. A total of 25 rabbits are used, which are divided into 5 groups. Under the general anesthesia is made the selective infusion of various doses of epinephrine into the right renal artery of the rabbits. At the various time interval during and after the epinephrine infusion, renal angiography was done, and 24 hrs. later, gross and microscopic findings of the kidney were observed. The results are as follows; 1. Vasoconstriction of renal artery occurred within 2 mins. infusion, and maximum effect within 5 mins. 2. It seems that there is correlation between the amount of infused epinephrine and the time taken to recover from constriction of renal artery. 3. When epinephrine is infused into the renal artery in the rate of 1 ug/min., renal infarct is not noticed below the level of 10 mins., but correlation between the amount of infused epinephrine and the frequency of renal infarct occurs above 20 mins. infusion

  2. Refractory hyperglycaemia induced by glucose-insulin-potassium infusion in acute myocardial infarction

    NARCIS (Netherlands)

    Svilaas, Tone; van der Horst, I.C.C.; Nijsten, M.W.N.; Zijlstra, F.

    2006-01-01

    Background. Recent randomised clinical trials have not confirmed the beneficial effects of glucose-insulin-potassium (GIK) infusion observed in experimental models of myocardial ischaemia and infarction. Methods. We investigated glucose levels and insulin dose in 107 patients treated with

  3. Fatty liver change as a result of hepatic artery infusion chemotherapy.

    Science.gov (United States)

    Zeiss, J; Merrick, H W; Savolaine, E R; Woldenberg, L S; Kim, K; Schlembach, P J

    1990-04-01

    Direct hepatic arterial infusion of floxuridine (FUDR) (Roche Laboratories, Division of Hoffman-LaRoche Inc., Nutley, NJ, U.S.A.) has been used extensively in the treatment of metastases of colorectal tumors to the liver. The effectiveness of infusion and tolerance of the chemotherapy has been improved utilizing a totally implantable infusion pump delivery system. However, unequal distribution of drug infusion may occur to different parts of the liver parenchyma as demonstrated by hepatic arterial infusion scintigraphy (HAPS). We present a case of such unequal perfusion in which fatty metamorphosis of the liver occurred in the overperfused liver segment after FUDR therapy. The liver parenchymal changes were followed by serial computerized tomography scans and proven by biopsy during a minilaparotomy. Serial HAPS examinations show redirection of subsequent infusion to the opposite liver lobe due to parenchymal damage and vascular sclerosis. The importance of uniform liver perfusion and a rare dose-related effect of FUDR on liver parenchyma are thereby demonstrated.

  4. Different transcriptional profiling between senescent and non-senescent human coronary artery endothelial cells (HCAECs) by Omeprazole and Lansoprazole treatment.

    Science.gov (United States)

    Costarelli, Laura; Giacconi, Robertina; Malavolta, Marco; Basso, Andrea; Piacenza, Francesco; Provinciali, Mauro; Maggio, Marcello G; Corsonello, Andrea; Lattanzio, Fabrizia

    2017-04-01

    Recent evidence suggests that high dose and/or long term use of proton pump inhibitors (PPIs) may increase the risk of adverse cardiovascular events in older patients, but mechanisms underlying these detrimental effects are not known. Taking into account that the senescent endothelial cells have been implicated in the genesis or promotion of age-related cardiovascular disease, we hypothesized an active role of PPIs in senescent cells. The aim of this study is to investigate the changes in gene expression occurring in senescent and non-senescent human coronary artery endothelial cells (HCAECs) following Omeprazole (OPZ) or Lansoprazole (LPZ) treatment. Here, we show that atherogenic response is among the most regulated processes in PPI-treated HCAECs. PPIs induced down-regulation of anti-atherogenic chemokines (CXCL11, CXCL12 and CX3CL1) in senescent but not in non-senescent cells, while the same chemokines were up-regulated in untreated senescent cells. These findings support the hypothesis that up-regulated anti-atherogenic chemokines may represent a defensive mechanism against atherosclerosis during cellular senescence, and suggest that PPIs could activate pro-atherogenic pathways by changing the secretory phenotype of senescent HCAECs. Moreover, the genes coding for fatty acid binding protein 4 (FABP4) and piezo-type mechanosensitive ion channel component 2 (PIEZO2) were modulated by PPIs treatment with respect to untreated cells. In conclusions, our results show that long-term and high dose use of PPI could change the secretory phenotype of senescent cells, suggesting one of the potential mechanisms by which use of PPI can increase adverse outcomes in older subjects.

  5. Impact of the reclassification of omeprazole on the prescribing and sales of ulcer healing drugs.

    Science.gov (United States)

    Dhippayom, Teerapon; Walker, Roger

    2006-08-01

    To investigate if the reclassification of omeprazole from a prescription only medicine to pharmacy sale status had an impact on the prescribing and sales of ulcer-healing drugs and whether deprivation had any influence on this. Primary care, Wales, UK. Retrospective analysis (March 2002 to February 2005) of prescription data and pharmacy sales data. Number of items per 1,000 population. The number of prescription items for ulcer-healing drugs across Wales increased in each year of the study. The number of items per 1,000 population for proton pump inhibitors increased by 12.4% (473.3 to 531.8 items) in 2003/04 and 13.8% (531.8 to 605.1 items) in 2004/05, whereas the number of items per 1,000 population for H2 antagonists fell by 6.2% (149.1 to 139.9 items), and 5.7% (139.9 to 131.9 items) during 2003/04 and 2004/05, respectively. The sale of items per 1,000 population of H(2) antagonists increased by 34.3% (19.8 to 26.6 items) in 2003/04, but fell by 8.6% (26.6 to 24.3 items) in 2004/05. In February 2005, 12 months after reclassification, omeprazole accounted for 7.6% (2.0 items per 1,000 population) of the total sales (26.3 items per 1,000 population) of ulcer-healing drugs from pharmacies in Wales. Areas with high multiple deprivation and unemployment were significantly associated with the prescribing of ulcer-healing drugs, H2 antagonists and proton pump inhibitors. Multiple deprivation, unemployment and low income explained 21% of the variation in prescribing of ulcer-healing drugs. The sale of omeprazole through pharmacies was not related to these deprivation characteristics. Twelve months after the reclassification of omeprazole the market growth of H2 antagonists sold from pharmacies was halted although there was no apparent impact on the prescription of ulcer-healing drugs. As a consequence there was no saving to the health service drug budget associated with the reclassification of omeprazole.

  6. Comparison of Omeprazole with Ranitidine for Treatment of Symptoms Associated with Gastroesophageal Reflux Disease and Uncomplicated Duodenal Ulcer

    Directory of Open Access Journals (Sweden)

    Andre P Archambault

    1996-01-01

    Full Text Available This randomized, single-blind, parallel group study was conducted to compare omeprazole with ranitidine for the treatment of symptoms associated with gastroesophageal reflux disease (GERD, uncomplicated duodenal ulcer (DU or both. After baseline assessments, patients were randomized to receive daily treatment with either 20 mg omeprazole or 300 mg ranitidine for four weeks. In total, 1481 patients (1001 omeprazole, 480 ranitidine with a diagnosis of GERD (n=904 and/or DU (n=577, confirmed by endoscopy or barium meal and reporting moderate to severe symptoms, were included in the analyses. The seventy of overall daytime symptoms reported by the omeprazole group at clinic visits was lower than that reported by the ranitidine group at week 2 for the entire patient group (P=0.0002 and at both weeks 2 and 4 for the subgroup of patients with GERD (P=0.0001 and P=0.001, respectively. The severity of overall night-time symptoms reported by the omeprazole group was lower than that reported by the ranitidine group at week 4 for all patients as a whole (P=0.042 and at both weeks 2 and 4 for the subgroup of patients with GERD (P=0.035 and P=0.010, respectively. There were no significant differences in reports of adverse events. In the omeprazole group, 19% of patients at week 2 and 15% of patients at week 4 reported adverse events, while the corresponding results from the ranitidine group were 21% and 11%. In conclusion, patients with GERD, DU or both treated with omeprazole 20 mg daily for four weeks showed statistically significant reductions in symptoms compared with patients treated with ranitidine 300 mg daily for the same period of time. The percentage of patients with any remaining daytime symptoms was 12% lower in the omeprazole group compared with the ranitidine group at week 2, and 7% lower at week 4. Five per cent fewer patients in the omeprazole group experienced night-time symptoms at either week 2 or week 4.

  7. Cardiovascular effects of dobutamine and phenylephrine infusion in sevoflurane-anesthetized Thoroughbred horses.

    Science.gov (United States)

    Ohta, Minoru; Kurimoto, Shinjiro; Ishikawa, Yuhiro; Tokushige, Hirotaka; Mae, Naomi; Nagata, Shun-ichi; Mamada, Masayuki

    2013-11-01

    To determine dose-dependent cardiovascular effects of dobutamine and phenylephrine during anesthesia in horses, increasing doses of dobutamine and phenylephrine were infused to 6 healthy Thoroughbred horses. Anesthesia was induced with xylazine, guaifenesin and thiopental and maintained with sevoflurane at 2.8% of end-tidal concentration in all horses. The horses were positioned in right lateral recumbency and infused 3 increasing doses of dobutamine (0.5, 1.0 and 2.0 µg/kg/min) for 15 min each dose. Following to 30 min of reversal period, 3 increasing doses of phenylephrine (0.25, 0.5 and 1.0 µg/kg/min) were infused. Cardiovascular parameters were measured before and at the end of each 15-min infusion period for each drug. Blood samples were collected every 5 min during phenylephrine infusion period. There were no significant changes in heart rate throughout the infusion period. Both dobutamine and phenylephrine reversed sevoflurane-induced hypotension. Dobutamine increased both mean arterial blood pressure (MAP) and cardiac output (CO) as the result of the increase in stroke volume, whereas phenylephrine increased MAP but decreased CO as the result of the increase in systemic vascular resistance. Plasma phenylephrine concentration increased dose-dependently, and these values at 15, 30 and 45 min were 6.2 ± 1.2, 17.0 ± 4.8 and 37.9 ± 7.3 ng/ml, respectively.

  8. Pharmacodynamics and kinetics of omeprazole MUPS 20 mg and pantoprazole 40 mg during repeated oral administration in Helicobacter pylori-negative subjects

    NARCIS (Netherlands)

    W.P. Geus; R.A. Mathot (Ron); P.G.H. Mulder (Paul); C.B.H.W. Lamers (C. B H W)

    2000-01-01

    textabstractBackground: Omeprazole has become available in a tablet formulation, a Multiple Unit Pellet System (MUPS) containing a large number of small individually enteric-coated micropellets. Aim: To compare the acid-inhibitory effect of omeprazole MUPS 20 mg with pantoprazole 40 mg and to

  9. The proton pump inhibitor, omeprazole, but not lansoprazole or pantoprazole, is a metabolism-dependent inhibitor of CYP2C19: implications for coadministration with clopidogrel.

    Science.gov (United States)

    Ogilvie, Brian W; Yerino, Phyllis; Kazmi, Faraz; Buckley, David B; Rostami-Hodjegan, Amin; Paris, Brandy L; Toren, Paul; Parkinson, Andrew

    2011-11-01

    As a direct-acting inhibitor of CYP2C19 in vitro, lansoprazole is more potent than omeprazole and other proton pump inhibitors (PPIs), but lansoprazole does not cause clinically significant inhibition of CYP2C19 whereas omeprazole does. To investigate this apparent paradox, we evaluated omeprazole, esomeprazole, R-omeprazole, lansoprazole, and pantoprazole for their ability to function as direct-acting and metabolism-dependent inhibitors (MDIs) of CYP2C19 in pooled human liver microsomes (HLM) as well as in cryopreserved hepatocytes and recombinant CYP2C19. In HLM, all PPIs were found to be direct-acting inhibitors of CYP2C19 with IC(50) values varying from 1.2 μM [lansoprazole; maximum plasma concentration (C(max)) = 2.2 μM] to 93 μM (pantoprazole; C(max) = 6.5 μM). In addition, we identified omeprazole, esomeprazole, R-omeprazole, and omeprazole sulfone as MDIs of CYP2C19 (they caused IC(50) shifts after a 30-min preincubation with NADPH-fortified HLM of 4.2-, 10-, 2.5-, and 3.2-fold, respectively), whereas lansoprazole and pantoprazole were not MDIs (IC(50) shifts lansoprazole, or pantoprazole, as irreversible (or quasi-irreversible) MDIs of CYP2C19. These results have important implications for the mechanism of the clinical interaction reported between omeprazole and clopidogrel, as well as other CYP2C19 substrates.

  10. Pharmacodynamics and kinetics of omeprazole MUPS 20 mg and pantoprazole 40 mg during repeated oral administration in Helicobacter pylori-negative subjects

    NARCIS (Netherlands)

    Geus, W. P.; Mathôt, R. A.; Mulder, P. G.; Lamers, C. B.

    2000-01-01

    Omeprazole has become available in a tablet formulation, a Multiple Unit Pellet System (MUPS) containing a large number of small individually enteric-coated micropellets. To compare the acid-inhibitory effect of omeprazole MUPS 20 mg with pantoprazole 40 mg and to describe the pharmacokinetics of

  11. Omeprazole, a specific inhibitor of gastric (H/sup +/-K/sup +/)-ATPase, is a H/sup +/-activated oxidizing agent of sulfhydryl groups

    Energy Technology Data Exchange (ETDEWEB)

    Im, W.B.; Sih, J.C.; Blakeman, D.P.; McGrath, J.P.

    1985-04-25

    Omeprazole (5-methoxy-2-(((4-methoxy-3,5- dimethylpyridinyl)methyl)sulfinyl)-1H-benzimidazole) appeared to inhibit gastric (H/sup +/-K/sup +/)-ATPase by oxidizing its essential sulfhydryl groups, since the gastric ATPase inactivated by the drug in vivo or in vitro recovered its K+-dependent ATP hydrolyzing activity upon incubation with mercaptoethanol. Biological reducing agents like cysteine or glutathione, however, were unable to reverse the inhibitory effect of omeprazole. Moreover, acidic environments enhanced the potency of omeprazole. The chemical reactivity of omeprazole with mercaptans is also consistent with the biological action of omeprazole. The N-sulfenylated compound reacted at neutral pH with another stoichiometric amount of ethyl mercaptan to produce omeprazole sulfide quantitatively. The gastric polypeptides of 100 kilodaltons representing (H/sup +/-K/sup +/)-ATPase in the rat gastric mucosa or isolated hog gastric membranes were covalently labeled with (/sup 14/C)omeprazole. The radioactive label bound to the ATPase, however, could not be displaced by mercaptoethanol under the identical conditions where the ATPase activity was fully restored. These observations suggest that the essential sulfhydryl groups which reacted with omeprazole did not form a stable covalent bond with the drug, but rather that they further reacted with adjacent sulfhydryl groups to form disulfides which could be reduced by mercaptoethanol.

  12. The effect of Helicobacter pylori eradication on intragastric pH during dosing with lansoprazole or ranitidine

    NARCIS (Netherlands)

    van Herwaarden, M. A.; Samsom, M.; van Nispen, C. H.; Mulder, P. G.; Smout, A. J.

    1999-01-01

    BACKGROUND: The antisecretory effect of omeprazole on intragastric pH is decreased in the absence of Helicobacter pylori. AIM: To investigate the effect of H. pylori eradication on intragastric pH during lansoprazole or ranitidine dosing in 41 asymptomatic H. pylori-positive subjects. METHOD: Two

  13. A double-blind placebo-controlled study on the effects of omeprazole on gut hormone secretion and gastric emptying rate

    DEFF Research Database (Denmark)

    Rasmussen, L; Qvist, N; Oster-Jørgensen, E

    1997-01-01

    BACKGROUND: The present study was designed to investigate whether an effect of omeprazole on gastric emptying is related to changes in the secretion of selected gut hormones. METHODS: The studies were performed in healthy men after 10 days' treatment with 40 mg omeprazole daily/placebo. Food...... ingestion took place in a duodenal phase, I and the meal consisted of an omelette labelled with technetium Tc 99m, followed by 150 ml water labelled with indium In 111. Plasma concentrations of gastrin, cholecystokinin (CCK), and motilin were measured. RESULTS: Pretreatment with omeprazole reduced gastric...... emptying rates. This applied to all variables and was most pronounced with regard to amounts of solid (median (95% confidence interval)) emptied at 180 min (71% (48 - 86) for omeprazole versus 96% (87 - 100) for placebo; P omeprazole...

  14. Comparison of Proton Pump Inhibitor and Histamine-2 Receptor Antagonist in the Prevention of Recurrent Peptic Ulcers/Erosions in Long-Term Low-Dose Aspirin Users: A Retrospective Cohort Study

    Directory of Open Access Journals (Sweden)

    Wen-Chi Chen

    2014-01-01

    Full Text Available Background. Proton pump inhibitor and histamine-2 receptor antagonist can prevent aspirin-related ulcers/erosions but few studies compare the efficacy of these two agents. Aims. We evaluated the efficacy of omeprazole and famotidine in preventing recurrent ulcers/erosions in low-dose aspirin users. Methods. The 24-week clinical outcomes of the patients using low-dose aspirin for cardiovascular protection with a history of ulcers/erosions and cotherapy of omeprazole or famotidine were retrospectively reviewed. The incidence of gastrointestinal symptoms, recurrent ulcers/erosions, erosive esophagitis, gastrointestinal bleeding, and thromboembolic events was analyzed. Results. A total of 104 patients (famotidine group, 49 patients; omeprazole group, 55 patients were evaluated. Famotidine group had more gastrointestinal symptoms episodes than omeprazole group (46.9% versus 23.6%, P=0.01. Fifteen famotidine group patients and 5 omeprazole group patients had recurrent ulcers/erosions (30.6% versus 9.1%, P=0.005. Lanza scale was significantly lower in omeprazole group than in famotidine group (1.2±0.7 versus 1.7±1.1, P=0.008. Only 1 famotidine group patient had ulcer bleeding. The incidences of erosive esophagitis and thromboembolic events were comparable between both groups. Conclusions. Omeprazole was superior to famotidine with less gastrointestinal symptoms and recurrent ulcers/erosions in patients using 24-week low-dose aspirin. The risk of erosive esophagitis, gastrointestinal bleeding, and thromboembolic events was similar between both groups.

  15. Reversibility of the cell kinetic changes induced by omeprazole in the rat oxyntic mucosa; An autoradiographic study using tritiated thymidine

    Energy Technology Data Exchange (ETDEWEB)

    Tielemans, Y.; Chen, D.; Sundler, F.; Haakanson, R.; Willems, G. (Vrije Univ., Brussels (Belgium))

    1992-01-01

    Both oxyntic mucosal progenitor cells and enterochromaffin-like (ECL) cells are under the trophic control of gastrin. The authors studied the effect of discontinuing omeprazole-induced hypergastrinemia on cell proliferation and ECL cell function in the rat oxyntic mucosa. All rats had hypergastrinemia after 16 days omeprazole administration, and the proliferation rate of both progenitor and ECL cells was increased, wheras it was decreased 5 days after withdrawal of omeprazole. Circulating gastrin had normalized by then. The proliferative activity of the progenitor cells returned to normal within 10 days, whereas that of the ECL cells remained suppressed for at least 20 days. The histidine decarboxylase activity of the ECL cells changed in parallel with their proliferative activity. These data suggest either a down-regulation of membrane receptors or the involvement of still unknown inhibitors of mitotic activity and ECL cell function in the oxyntic mucosa. 33 refs., 6 figs.

  16. Relevancia clínica de la interacción clopidogrel y omeprazol: revisión sistemática Clinical relevance of clopidogrel and omeprazole interaction: systematic review

    Directory of Open Access Journals (Sweden)

    Héctor Holguín

    2012-01-01

    Full Text Available Objetivo: realizar una revisión estructurada de la interacción clopidogrel y omeprazol, establecer su relevancia clínica y generar recomendaciones prácticas respecto al tema. Método: revisión estructurada en PubMed/MedLine de trabajos publicados en los últimos diez años, utilizando como estrategia clopidogrel AND omeprazole. La información se agrupó y complementó acorde con el método utilizado para la cuantificación del efecto y con la determinación de un posible efecto de clase. Resultados: la búsqueda generó 35 artículos, de ellos se incluyeron 18 (cinco valoraron la interacción in-vitro, seis la interacción in-vivo y diez la interacción como un efecto de clase. Siete estudios reportaron pérdida del efecto antiagregante, mientras que tres no encontraron una alteración relevante del mismo. Conclusiones: la evidencia de la relevancia clínica de la interacción clopidogrel y omeprazol no es concluyente. Se recomienda seguir las indicaciones de las agencias regulatorias y, en algunos casos, sustituir omeprazol por pantoprazol.Objective: to perform a structured review of the clopidogrel and omeprazole interaction, establish its clinical relevance and generate practical recommendations on the subject. Method: a structured review on PubMedLine of studies published in the last ten years, using clopidogrel AND omeprazole as strategy. The information was grouped and complemented according to the method used to quantify the effect and with the determination of a possible class effect. Results: the search generated 35 articles, of which 18 were included (five assessed the in-vitro interaction, six the in-vivo interaction and ten analyzed the interaction as a class effect. Seven studies reported loss of the platelet anti-aggregation effect, while three found no significant alteration of the effect. Conclusions: the evidence of the clinical relevance of clopidogrel and omeprazole interaction is nor conclusive. It is recommended to

  17. Transarterial Infusion Chemotherapy Using Cisplatin-Lipiodol Suspension With or Without Embolization for Unresectable Hepatocellular Carcinoma

    International Nuclear Information System (INIS)

    Kawaoka, Tomokazu; Aikata, Hiroshi; Takaki, Shintaro; Katamura, Yoshio; Hiramatsu, Akira; Waki, Koji; Takahashi, Shoichi; Hieda, Masashi; Toyota, Naoyuki; Ito, Katsuhide; Chayama, Kazuaki

    2009-01-01

    We evaluate the long-term prognosis and prognostic factors in patients treated with transarterial infusion chemotherapy using cisplatin-lipiodol (CDDP/LPD) suspension with or without embolization for unresectable hepatocellular carcinoma (HCC). Study subjects were 107 patients with HCC treated with repeated transarterial infusion chemotherapy alone using CDDP/LPD (adjusted as CDDP 10mg/LPD 1ml). The median number of transarterial infusion procedures was two (range, one to nine), the mean dose of CDDP per transarterial infusion chemotherapy session was 30 mg (range, 5.0-67.5 mg), and the median total dose of transarterial infusion chemotherapy per patient was 60 mg (range, 10-390 mg). Survival rates were 86% at 1 year, 40% at 3 years, 20% at 5 years, and 16% at 7 years. For patients with >90% LPD accumulation after the first transarterial infusion chemotherapy, rates were 98% at 1 year, 60% at 3 years, and 22% at 5 years. Multivariate analysis identified >90% LPD accumulation after the first transarterial infusion chemotherapy (p = 0.001), absence of portal vein tumor thrombosis (PVTT; p < 0.001), and Child-Pugh class A (p = 0.012) as independent determinants of survival. Anaphylactic shock was observed in two patients, at the fifth transarterial infusion chemotherapy session in one and the ninth in the other. In conclusion, transarterial infusion chemotherapy with CDDP/LPD appears to be a useful treatment option for patients with unresectable HCC without PVTT and in Child-Pugh class A. LPD accumulation after the first transarterial infusion chemotherapy is an important prognostic factor. Careful consideration should be given to the possibility of anaphylactic shock upon repeat infusion with CDDP/LPD.

  18. Differential effects of omeprazole and lansoprazole enantiomers on aryl hydrocarbon receptor in human hepatocytes and cell lines.

    Science.gov (United States)

    Novotna, Aneta; Srovnalova, Alzbeta; Svecarova, Michaela; Korhonova, Martina; Bartonkova, Iveta; Dvorak, Zdenek

    2014-01-01

    Proton pump inhibitors omeprazole and lansoprazole contain chiral sulfur atom and they are administered as a racemate, i.e. equimolar mixture of S- and R-enantiomers. The enantiopure drugs esomeprazole and dexlansoprazole have been developed and introduced to clinical practice due to their improved clinical and therapeutic properties. Since omeprazole and lansoprazole are activators of aryl hydrocarbon receptor (AhR) and inducers of CYP1A genes, we examined their enantiospecific effects on AhR-CYP1A pathway in human cancer cells and primary human hepatocytes. We performed gene reporter assays for transcriptional activity of AhR, RT-PCR analyses for CYP1A1/2 mRNAs, western blots for CYP1A1/2 proteins and EROD assay for CYP1A1/2 catalytic activity. Lansoprazole and omeprazole enantiomers displayed differential effects on AhR-CYP1A1/2 pathway. In general, S-enantiomers were stronger activators of AhR and inducers of CYP1A genes as compared to R-enantiomers in lower concentrations, i.e. 1-10 µM for lansoprazole and 10-100 µM for omeprazole. In contrast, R-enantiomers were stronger AhR activators and CYP1A inducers than S-enantiomers in higher concentrations, i.e. 100 µM for lansoprazole and 250 µM for omeprazole. In conclusion, we provide the first evidence of enantiospecific effects of omeprazole and lansoprazole on AhR signaling pathway.

  19. A pilot study comparing the effect of orally administered esomeprazole and omeprazole on gastric fluid pH in horses.

    Science.gov (United States)

    Huxford, K E; Dart, A J; Perkins, N R; Bell, R; Jeffcott, L B

    2017-11-01

    AIMS To compare the efficacy of an enteric coated esomeprazole paste with an enteric coated omeprazole paste to increase gastric pH after oral administration in horses. METHODS Nine adult Standardbred horses were randomly assigned to three groups, each containing three horses, for a study comprising three phases of 10 days, with an 18-day washout period between each phase. In each phase, three horses received either 0.5 mg/kg esomeprazole, 1 mg/kg omeprazole or a placebo, as an oral paste, once daily for 10 days (Days 0-9). Over the course of study all horses received all three treatments. Gastric fluid samples were collected using a gastroscope on Days 1, 3, 5, 8 and 10, with food and water withheld for 16 hours prior to collection of samples. The pH of all samples was measured immediately after collection. RESULTS Mean pH (3.38; SD 1.75) of the gastric fluid samples in the horses that received the placebo was lower than in the horses that received esomeprazole (6.28; SD 1.75) or omeprazole (6.13; SD 1.75) (p<0.001). There was no difference in the mean pH between horses receiving esomeprazole and those receiving omeprazole (p=0.56). CONCLUSIONS AND CLINICAL RELEVANCE Under these study conditions, esomeprazole paste was equally as effective as omeprazole paste in increasing gastric pH in horses. Enteric coated esomeprazole, may be a therapeutic alternative to omeprazole for the prevention of gastric ulcers in horses.

  20. Residual solvent determination by head space gas chromatography with flame ionization detector in omeprazole API

    Directory of Open Access Journals (Sweden)

    Saurabh Pandey

    2011-06-01

    Full Text Available Residual solvents in pharmaceutical samples are monitored using gas chromatography with head space. Based on good manufacturing practices, measuring residual solvents is mandatory for the release testing of all active pharmaceutical ingredients (API. The analysis of residual organic solvents (methanol, acetone, cyclohexane, dichloromethane, toluene in Omeprazole, an active pharmaceutical ingredient was investigated. Omeprazole is a potent reversible inhibitor of the gastric proton pump H+/K+-ATPase. The Head space gas chromatography (HSGC method described in this investigation utilized a SPB TM-624, Supelco, 30 m long x 0.25 mm internal diameter, 1.4µm-thick column. Since Omeprazole is a thermally labile compound, the selection of the proper injector temperature is critical to the success of the analysis. The injector temperature was set at 170ºC to prevent degradation. The initial oven temperature was set at 40ºC for 12 min and programmed at a rate of 10ºC min-1 to a final temperature of 220ºC for 5 min. Nitrogen was used as a carrier gas. The sample solvent selected was N,N-dimethylacetamide. The method was validated to be specific, linear, precise, sensitive, rugged and showed excellent recovery.Solventes residuais em amostras farmacêuticas são monitoradas utilizando-se cromatografia a gás "headspace". Com base nas boas práticas de fabricação, a medida de solventes residuais é obrigatória para o teste de liberação de todos os ingredientes farmacêuticos (API. Efetuou-se a análise de solventes orgânicos residuais (metanol, acetona, cicloexano, diclorometano, tolueno em omeprazol, ingrediente farmacêutico ativo. O omeprazol é potente inibidor reversível da bomba de prótons H+/K+-ATPase. A cromatografia a gás "headspace" (HSGC descrita nessa pesquisa utilizou um SPB TM-624, Supelco, de 30 m de comprimento x 0,25 mm de diâmetro interno, e coluna de 1,4 µm de espessura. Considerando-se que o omeprazol é termicamente l

  1. Omeprazole Attenuates Pulmonary Aryl Hydrocarbon Receptor Activation and Potentiates Hyperoxia-Induced Developmental Lung Injury in Newborn Mice.

    Science.gov (United States)

    Shivanna, Binoy; Zhang, Shaojie; Patel, Ananddeep; Jiang, Weiwu; Wang, Lihua; Welty, Stephen E; Moorthy, Bhagavatula

    2015-11-01

    Hyperoxia contributes to the development of bronchopulmonary dysplasia (BPD) in human preterm infants and a similar lung phenotype characterized by alveolar simplification in newborn mice. Omeprazole (OM) is a proton pump inhibitor that is used to treat humans with gastric acid related disorders. OM-mediated aryl hydrocarbon receptor (AhR) activation attenuates acute hyperoxic lung injury (HLI) in adult mice. Whether OM activates pulmonary AhR and protects C57BL/6J newborn mice against hyperoxia-induced developmental lung (alveolar and pulmonary vascular simplification, inflammation, and oxidative stress) injury (HDLI) is unknown. Therefore, we tested the hypothesis that OM will activate pulmonary AhR and mitigate HDLI in newborn mice. Newborn mice were treated daily with i.p. injections of OM at doses of 10 (OM10) or 25 (OM25) mg/kg while being exposed to air or hyperoxia (FiO2 of 85%) for 14 days, following which their lungs were harvested to determine alveolarization, pulmonary vascularization, inflammation, oxidative stress, vascular injury, and AhR activation. To our surprise, hyperoxia-induced alveolar and pulmonary vascular simplification, inflammation, oxidative stress, and vascular injury were augmented in OM25-treated animals. These findings were associated with attenuated pulmonary vascular endothelial growth factor receptor 2 expression and decreased pulmonary AhR activation in the OM25 group. We conclude that contrary to our hypothesis, OM decreases functional activation of pulmonary AhR and potentiates HDLI in newborn mice. These observations are consistent with our previous findings, which suggest that AhR activation plays a protective role in HDLI in newborn mice. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  2. Dialysis Access Graft Thrombolysis: Randomized Study of Pulse-Spray Versus Continuous Urokinase Infusion

    International Nuclear Information System (INIS)

    Goodwin, Scott C.; Arora, Lokesh C.; Razavi, Mahmood K.; Sayre, James; McNamara, Thomas O.; Yoon, Chun

    1998-01-01

    Purpose: To compare pulse-spray to continuous-infusion thrombolysis with high-dose urokinase in thrombosed dialysis access grafts. Methods: A prospective randomized controlled trial was performed. From August 1992 to September 1993, 30 thrombosed polytetrafluoroethylene (PTFE) grafts in 24 patients were included, 15 grafts in each group. The success of thrombolysis, mean time to thrombolysis, mean urokinase dose, and 60-day patency rate were evaluated. Results: In the pulse-spray group, the mean time to thrombolysis was 72 min with a mean urokinase dose of 560,000 U. The 60-day patency rate was 71%. In the continuous-infusion group, the mean infusion time to thrombolysis was 55 min with a mean dose of 479,000 U. The 60-day patency rate was 73%. Conclusion: No statistically significant difference was found between the two techniques in the mean time to thrombolysis, the mean urokinase dose used, or the 60-day patency rate

  3. Comparative study of omeprazole, lansoprazole, pantoprazole and esomeprazole for symptom relief in patients with reflux esophagitis

    Science.gov (United States)

    Zheng, Ri-Nan

    2009-01-01

    AIM: To clarify whether there is any difference in the symptom relief in patients with reflux esophagitis following the administration of four Proton pump inhibitors (PPIs). METHODS: Two hundred and seventy-four patients with erosive reflux esophagitis were randomized to receive 8 wk of 20 mg omeprazole (n = 68), 30 mg of lansoprazole (n = 69), 40 mg of pantoprazole (n = 69), 40 mg of esomeprazole (n = 68) once a day in the morning. Daily changes in heartburn and acid reflux symptoms in the first 7 d of administration were assessed using a six-point scale (0: none; 1: mild; 2: mild-moderate; 3: moderate; 4: moderate-severe; 5: severe). RESULTS: The mean heartburn score in patients treated with esomeprazole more rapidly decreased than those receiving other PPI. Complete resolution of heartburn was also more rapid in patients treated with esomeprazole for 5 d compared with omeprazole (P = 0.0018, P = 0.0098, P = 0.0027, P = 0.0137, P = 0.0069, respectively), lansoprazole (P = 0.0020, P = 0.0046, P = 0.0037, P = 0.0016, P = 0.0076, respectively), and pantoprazole (P = 0.0006, P = 0.0005, P = 0.0009, P = 0.0031, P = 0.0119, respectively). There were no significant differences between the four groups in the rate of endoscopic healing of reflux esophagitis at week 8. CONCLUSION: Esomeprazole may be more effective than omeprazole, lansoprazole, and pantoprazole for the rapid relief of heartburn symptoms and acid reflux symptoms in patients with reflux esophagitis. PMID:19248200

  4. Características de las dispensaciones de omeprazol en una farmacia comunitaria

    Directory of Open Access Journals (Sweden)

    Ezquieta MF

    2010-06-01

    Full Text Available INTRODUCCIÓN Omeprazol es uno de los principios que más se dispensa en la farmacia comunitaria. Pertenece al grupo de los inhibidores de la bomba de protones (IBP y actúa inhibiendo la secreción de H+ al estómago, disminuyendo en consecuencia los síntomas derivados de una excesiva acidez gástrica. OBJETIVOS Estudiar las características de la utilización de omeprazol 20 mg por los pacientes en una farmacia comunitaria, tratando de investigar las causas de la elevada prevalencia de uso de este medicamento entre dicha población. RESULTADOS La primera prescripción fue del médico de familia en un 59% de los casos y del especialista en el 41%. Un 61% de los pacientes dejó de tomarlo y tuvo que volver por sentir molestias gástricas. Un 44% no sabe hasta cuándo tiene que tomarlo y un 35% cree que debe tomarlo siempre. Un 55% lo toma por estar tomando al mismo tiempo un AINE. DISCUSIÓN Este estudio se encuentra limitado por el reducido número de encuestas en una sola farmacia comunitaria. Los resultados apuntan a que las causas de la elevada utilización de omeprazol pueden ser varias: el uso de AINE durante largos periodos de tiempo en dosis elevadas, el envejecimiento de la población que necesita utilizar un AINE como antiagregante o toma varios medicamentos, el uso en indicaciones poco precisas o el empleo para afecciones gástricas menores y la gastroprotección en pacientes polimedicados sin factores de riesgo. Otro factor que también podría influir es el posible rebote ácido tras la supresión del tratamiento, que deriva en la utilización crónica del medicamento.

  5. Rapid Infliximab Infusion in Children with Inflammatory Bowel Disease: A Multicenter North American Experience.

    Science.gov (United States)

    El-Matary, Wael; Dykes, Dana M H; Bauman, Laura; Elkadri, Abdul; Carroll, Matthew W; Izaguirre, Marisa R; deBruyn, Jennifer; Samson, Charles M; Crim, Alisa Muniz; Ali, Sabina; Grossman, Andrew

    2017-12-01

    Infliximab (IFX) infusion may lead to development of anti-IFX antibodies, and subsequent infusion reactions (IRs). The safety of rapid IFX infusion administered over 60 minutes has been under-investigated in children with inflammatory bowel disease. In a multicenter study, the frequency and nature of rapid infusion-associated IRs were examined. The medical records of all consecutive children with inflammatory bowel disease receiving rapid IFX infusions between January 2014 and December 2016 were reviewed. Poisson regression analysis was used to identify possible associated factors with IRs. A total of 4120 rapid infusions for 453 children (median age 16 yrs [interquartile range 13.8-17.8], 289 males, 374 with Crohn's disease) were included. One hundred thirty-five participants (29.8%) received rapid IFX infusion for induction and maintenance while the rest received rapid IFX infusion after a median of 5 (interquartile range 4-9) standard infusions. The median dose of IFX using rapid protocol was 8 mg/kg/infusion (interquartile range 6-10). Two hundred sixty-seven (59%) patients received 1 or more premedications and 161 (35.5%) participants received concomitant immunosuppression. Twenty-one participants (4.6%) had IRs with rapid infusions and 2 participants discontinued IFX because of IRs (0.4%). Antihistamine premedications were associated with less frequent IR (adjusted relative risk = 0.30; 95% confidence interval, 0.14-0.64; P = 0.002). In children with inflammatory bowel disease, rapid IFX infusion administered over 60 minutes is safe and well-tolerated. Antihistamine premedications may reduce frequency of IRs (see Video Abstract, Supplemental Digital Content 1, http://links.lww.com/IBD/B632).

  6. Oxidation of R- and S-omeprazole stereoselectively mediated by liver microsomal cytochrome P450 2C19 enzymes from cynomolgus monkeys and common marmosets.

    Science.gov (United States)

    Uehara, Shotaro; Kawano, Mirai; Murayama, Norie; Uno, Yasuhiro; Utoh, Masahiro; Inoue, Takashi; Sasaki, Erika; Yamazaki, Hiroshi

    2016-11-15

    Racemic omeprazole has been used for clinically treating gastric acid-related diseases and also as a typical human cytochrome P450 (P450) 2C19 probe substrate in preclinical studies. S-Omeprazole has been developed as a single enantiomer medicine, which has been reported not to be associated with polymorphic human P450 2C19 phenotypes. In this study, 5-hydroxylation and sulfoxidation activities, with respect to stereoselective R- and S-omeprazole oxidations by liver microsomes from experimental animals including non-human primates and humans, were investigated in vitro. Liver microsomes from humans, cynomolgus monkeys, and mice preferentially mediated R-omeprazole 5-hydroxylations, however those from marmosets, minipigs, dogs, and rats preferentially mediated S-omeprazole 5-hydroxylations. High catalytic activities were observed for recombinant human P450 2C19 in R-omeprazole 5-hydroxlations, cynomolgus monkey P450 2C19 in both R- and S-omeprazole 5-hydroxlations, and marmoset P450 2C19 in S-omeprazole 5-hydroxlations. On the other hand, human, cynomolgus monkey, and marmoset P450 3A enzymes preferentially mediated S-omeprazole sulfoxidations. Correlation and kinetic analyses revealed a high affinity of polymorphic cynomolgus monkey and marmoset liver microsomal P450 2C19 enzymes with respect to R- and S-omeprazole 5-hydroxylations, respectively, and a high capacity of cynomolgus monkey and marmoset liver microsomal P450 3A4 for omeprazole 5-hydroxylations and sulfoxidations. R-and S-omeprazole 5-hydroxylation activities in cynomolgus monkey and marmoset liver microsomes were significantly different among wild-type, heterozygous, and homozygous animals genotyped for cynomolgus monkey P450 2C19 p.[(Phe100Asn; Ala103Val; Ile112Leu)] and for marmoset P450 2C19 p.[(Phe7Leu; Ser254Leu; Ile469Thr)], respectively. The results of this study demonstrate polymorphic cynomolgus monkey and marmoset P450 2C19-dependent omeprazole oxidation activities with individual variations

  7. Neutron activation analysis of chemical impurities in manipulated samples of omeprazole

    International Nuclear Information System (INIS)

    Sepe, Fernanda Peixoto; Leal, Alexandre Soares; Gomes, Tatiana Cristina Bomfim; Menezes, Maria Angela de Barros Correia; Silva, Maria Aparecida

    2011-01-01

    In this work, samples of Omeprazole (C 17 H 19 N 3 O 3 S), a largely used drug in the treatment of dyspepsia and peptic ulcer, were acquired from five different pharmacies of manipulation - or retail pharmacies which prepare personalized drugs under medical recommendation - in Belo Horizonte/Brazil and investigated using the k 0 - Neutron Activation Analysis (NAA). The preliminary results showed the presence of elements not foreseen in the original formula. It confirms the potential risk offered by medicines without suitable inspection. (author)

  8. Oesophageal lumen pH in yearling horses and effects of management and administration of omeprazole.

    Science.gov (United States)

    Wilson, C S; Brookes, V J; Hughes, K J; Trope, G D; Ip, H; Gunn, A J

    2017-05-01

    In human subjects, arytenoid chondritis can be caused by chemical trauma of mucosa attributable to gastro-oesophageal reflux. Although a similar process may be involved in the aetiopathogenesis of arytenoid chondritis in horses, the oesophageal lumen pH in this species is poorly understood. To determine if gastro-oesophageal reflux occurs in horses by characterising oesophageal lumen pH. Blinded, randomised, placebo-controlled, crossover, experimental study. Luminal oesophageal pH in six yearling horses was recorded over four 24 h periods using an ambulatory pH recorder attached to a catheter with two electrodes (proximal and distal) inserted into the oesophagus. Recordings of pH were made during three management protocols. Initially, horses grazed in a paddock (Protocol A). Horses were then moved to stables to simulate sale preparation of Thoroughbred yearlings, and were given either omeprazole (Protocol B) or placebo paste (Protocol C) orally once per day. Protocol A was repeated for each horse (after a 13 day washout period) between Protocols B and C. Summary statistics described pH range and frequency of pH changes. Associations with predictor variables were investigated using linear mixed-effects models. Data are presented as the mean ± s.d. Oesophageal lumen pH ranged from 4.90 to 9.70 (7.36 ± 0.27 and 7.18 ± 0.24 for the proximal and distal electrodes, respectively) and varied frequently (1.2 ± 0.9 changes/min and 0.8 ± 0.8 changes/min for the proximal and distal electrodes, respectively). Oesophageal lumen pH was associated with time since concentrate feeding, activity and time of day, but not with treatment of omeprazole. A small number of horses were used and measurement periods were limited. Gastro-oesophageal reflux occurs in clinically normal yearling horses. Although omeprazole had no detectable effect, oesophageal lumen pH recorded during this study did not fall within the therapeutic range of omeprazole. © 2016 EVJ Ltd.

  9. Esophageal Acidification During Nocturnal Acid-breakthrough with Ilaprazole Versus Omeprazole in Gastroesophageal Reflux Disease.

    Science.gov (United States)

    Karyampudi, Arun; Ghoshal, Uday C; Singh, Rajan; Verma, Abhai; Misra, Asha; Saraswat, Vivek A

    2017-04-30

    Though nocturnal acid-breakthrough (NAB) is common in gastroesophageal reflux disease (GERD) patients, its clinical importance results from esophageal acidification, which has been shown to be uncommon. Ilaprazole, a long-acting proton pump inhibitor, may cause NAB infrequently. Accordingly, we studied prospectively, (1) frequency and degree of esophageal acidification during NAB, and (2) frequency and severity of NAB while on ilaprazole versus omeprazole. Fifty-eight consecutive patients with GERD on once daily ilaprazole, 10 mg (n = 28) or omeprazole, 20 mg (n = 30) for > one month underwent 24-hour impedance-pH monitoring prospectively. NAB was defined as intra-gastric pH one hour during night, and esophageal acidification as pH < 4 for any duration. Nocturnal symptoms (heartburn, regurgitation, and chest pain) were also recorded. Of the 58 patients (age 35.5 [inter-quartile range 26.5-46.0] years, 38 [65.5%], 42 (72.4%) had NAB. Though patients with NAB had lower nocturnal intra-gastric pH than without (2.8 [1.9-4.1] vs 5.7 [4.6-6.8], P < 0.001), frequency and duration of nocturnal esophageal acidification (17/42 vs 4/16, P = 0.360 and 0.0 [0.0-1.0] vs 0.0 [0.0-0.3] minutes, P = 0.260, respectively) and symptoms were comparable (13/42 vs 6/16, P = 0.750). Though ilaprazole was associated with less NABs (1 [range 1-2, n = 19] vs 1 [range 1-3, n = 23], P = 0.010) than omeprazole, the frequency, duration, and mean intra-gastric pH during NAB were comparable (19/28 vs 23/30, P = 0.560; 117 [0-315] vs 159 [69-287] minutes, P = 0.500; 1.02 [0.7-1.4] vs 1.04 [0.44-1.3], P = 0.620, respectively). Though NAB was common while patients were on a proton pump inhibitor, esophageal acidification was uncommon. Frequency and severity of NAB were comparable among patients on ilaprazole and omeprazole, except for the lesser number of NABs with ilaprazole.

  10. Neutron activation analysis of chemical impurities in manipulated samples of omeprazole

    Energy Technology Data Exchange (ETDEWEB)

    Sepe, Fernanda Peixoto; Leal, Alexandre Soares; Gomes, Tatiana Cristina Bomfim; Menezes, Maria Angela de Barros Correia; Silva, Maria Aparecida, E-mail: asleal@cdtn.br [Nuclear Technology Development Centre/Brazilian Commission for Nuclear Energy (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil)

    2011-07-01

    In this work, samples of Omeprazole (C{sub 17}H{sub 19}N{sub 3}O{sub 3}S), a largely used drug in the treatment of dyspepsia and peptic ulcer, were acquired from five different pharmacies of manipulation - or retail pharmacies which prepare personalized drugs under medical recommendation - in Belo Horizonte/Brazil and investigated using the k{sub 0} - Neutron Activation Analysis (NAA). The preliminary results showed the presence of elements not foreseen in the original formula. It confirms the potential risk offered by medicines without suitable inspection. (author)

  11. Boron biodistribution in Beagles after intravenous infusion of 4-dihydroxyborylphenylalanine-fructose complex

    International Nuclear Information System (INIS)

    Kulvik, M.E.; Vaehaetalo, J.K.; Benczik, J.; Snellman, M.; Laakso, J.; Hermans, R.; Jaerviluoma, E.; Rasilainen, M.; Faerkkilae, M.; Kallio, M.E.

    2004-01-01

    Boron biodistribution after intravenous infusion of 4-dihydroxyborylphenylalanine-fructose (BPA-F) complex was investigated in six dogs. Blood samples were evaluated during and following doses of 205 and 250 mg/kgbw BPA in a 30 min infusion, and 500 mg/kgbw in a 1 h infusion. Samples from whole blood, urine, brain and other organs were analysed for boron content after varying times following the onset of infusion. The whole blood boron concentrations declined from 27 to 8.4 ppm over the period of 39-165 min after the onset of infusion and the levels increased from 1.9 to 12 ppm in the grey matter of the brain over the same period. The boron concentrations in whole blood decreased steadily, whereas the boron values in brain tissue rose steadily with time. It was concluded that whole blood boron concentrations do not seem to reflect accurately the boron concentration in brain tissue at respective time points

  12. 21 CFR 880.5725 - Infusion pump.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Infusion pump. 880.5725 Section 880.5725 Food and... Infusion pump. (a) Identification. An infusion pump is a device used in a health care facility to pump fluids into a patient in a controlled manner. The device may use a piston pump, a roller pump, or a...

  13. Safety, local tolerability and pharmacokinetics of ceftaroline fosamil administered in a reduced infusion volume.

    Science.gov (United States)

    Edeki, Timi; Kujacic, Mirjana; Broadhurst, Helen; Li, Jianguo; Sunzel, Maria

    2014-12-01

    The standard dose of ceftaroline fosamil for patients with normal renal function is 600 mg diluted in 250 ml by 60 min intravenous infusion every 12 h. This two part phase I trial (NCT01577589) assessed safety and local tolerability of multiple ceftaroline fosamil 50 ml and 250 ml infusions, and pharmacokinetics following single administrations of each infusion volume. Part A was a placebo-controlled, double-blind, multiple dose crossover study. Twenty-four healthy subjects were randomized to simultaneous, bilateral ceftaroline fosamil 600 mg and placebo infusions in each arm (50 ml then 250 ml or vice versa) every 12 h for 72 h, with a ≥ 4.5 day washout. Local tolerability was evaluated by the Visual Infusion Phlebitis scale, with scores ≥2 considered infusion site reactions (ISRs). Part B was an open label crossover study. Ten subjects were randomized to single 50 ml and 250 ml ceftaroline fosamil 600 mg infusions on days 1 and 3 (washout on day 2). Blood samples for pharmacokinetic analysis were taken over 24 h. In part A, four subjects (16.7%) experienced ISRs, all of which were associated with placebo infusions. No ISRs were reported for either ceftaroline fosamil 50 ml or 250 ml. Plasma pharmacokinetics (ceftaroline fosamil, active ceftaroline and an inactive metabolite) were similar following single 50 ml and 250 ml infusions in part B. No new safety concerns were identified for ceftaroline fosamil 600 mg 50 ml compared with 250 ml. These findings suggest infusion volumes down to 50 ml may be used in patients with fluid intake restrictions. © 2014 The British Pharmacological Society.

  14. FIRST-ROW TRANSITION METAL COMPLEXES OF OMEPRAZOLE AS ANTI-ULCERATIVE DRUGS

    Directory of Open Access Journals (Sweden)

    Suman Malik

    2010-12-01

    Full Text Available Omeprazole (OME is a proton pump inhibitor (PPI. PPIs have enabled to improve the treatment of various acid-peptic disorders. OME is a weak base and it can form several complexes with transition and non-transition metal ions. In the present paper, we are describing series of transition metal complexes of omeprazole i.e., 5-methoxy-2[(4methoxy-3, 5dimethyl-2-pyridinyl methylsulfinyl]-1H-benzimidazole with CuII, MnII, CoII, NiII, FeII, ZnII and HgII. These complexes were characterized by elemental analysis, molar conductivity, IR, NMR, magnetic susceptibility, UV-visible spectral studies, ESR, SEM and X-ray diffraction. Based on the above studies, the ligand behaves as bidentate O, N donor and forms coordinate bonds through C=N and S=O groups. The complexes were found to non-electrolytic in nature on the basis of low values of molar conductivity. Analytical data and stoichiometry analysis suggest ligand to metal ratio of 2:1 for all the complexes. Electronic spectra and magnetic susceptibility measurements reveal octahedral geometry for Mn(II,Co(II, Ni(II,Fe(II and Cu(II complexes and tetrahedral for Hg(II and Zn(II complexes. Ligands and their metal complexes have been screened for their antibacterial and antifungal activities against bacteria Pseudomonas, Staphylococcus aureus and fungi Aspergillus niger and A. flavous.

  15. An assessment of the variation in the concentration of acetylcysteine in infusions for the treatment of paracetamol overdose.

    Science.gov (United States)

    Bailey, George P; Wood, David M; Archer, John R H; Rab, Edmund; Flanagan, Robert J; Dargan, Paul I

    2017-02-01

    Intravenous acetylcysteine is the treatment of choice for paracetamol poisoning. A previous UK study in 2001 found that 39% of measured acetylcysteine infusion concentrations differed by >20% from anticipated concentrations. In 2012, the UK Commission on Human Medicines made recommendations for the management of paracetamol overdose, including provision of weight-based acetylcysteine dosing tables. The aim of this study was to assess variation in acetylcysteine concentrations in administered infusions following the introduction of this guidance. A 6-month single-centre prospective study was undertaken at a UK teaching hospital. After preparation, 5-ml samples were taken from the first, second and third/any subsequent acetylcysteine infusions. Acetylcysteine was measured in diluted (1:50) samples by high-performance liquid chromatography. Comparisons between measured and expected concentrations based on prescribed weight-based dose and volume were made for each infusion. Ninety samples were collected. There was a variation of ≤10% in measured compared to expected concentration for 45 (50%) infusions, of 10-20% for 27 (30%) infusions, 20.1-50% for 14 (16%) infusions and >50% for four (4%) infusions. There was a median (interquartile range) variation in measured compared to expected concentration of -3.6 mg ml -1 (-6.7 to -2.3) for the first infusion, +0.2 mg ml -1 (-0.9 to +0.4) for the second infusion and -0.3 mg ml -1 (-0.6 to +0.2) for third and fourth infusions. There has been a moderate improvement in the variation in acetylcysteine dose administered by infusion. Further work is required to understand the continuing variation and consideration should be given to simplification of acetylcysteine regimes to decrease the risk of administration errors. © 2016 The British Pharmacological Society.

  16. Clopidogrel and proton pump inhibitor (PPI interaction: separate intake and a non-omeprazole PPI the solution?

    Directory of Open Access Journals (Sweden)

    Kenngott S

    2010-05-01

    Full Text Available Abstract Background Dual therapy with aspirin and clopidogrel increases the risk of gastrointestinal bleeding. Therefore, co-therapy with a proton pump inhibitor (PPI is recommended by most guidelines. However, there are warnings against combining PPIs with clopidogrel because of their interactions with cytochrome P450 isoenzyme 2C19 (CYP2C19. Methods The effects of the combined or separate intake of 20 mg of omeprazole and 75 mg of clopidogrel on the clopidogrel-induced inhibition of platelet aggregation were measured in four healthy subjects whose CYP2C19 exon sequences were determined. The effects of co-therapy with 10 mg of rabeprazole were also examined. Results Two subjects showed the wild-type CYP2C19 sequence. The concurrent intake of omeprazole had no effect on clopidogrel-induced platelet inhibition in these subjects. Two subjects were heterozygous for the *2 allele, with predicted reduced CYP2C19 activity. One of them was a clopidogrel non-responder. In the second heterozygous subject, omeprazole co-therapy reduced the clopidogrel anti-platelet effect when taken simultaneously or separately. However, the simultaneous intake of rabeprazole did not reduce the clopidogrel effect. Conclusion The clopidogrel-PPI interaction does not seem to be a PPI class effect. Rabeprazole did not affect the clopidogrel effect in a subject with a clear omeprazole-clopidogrel interaction. The separate intake of PPI and clopidogrel may not be sufficient to prevent their interaction.

  17. Gestão das inovações incrementais, o caso Omeprazola Management of incremental innovations, the case Omeprazole

    Directory of Open Access Journals (Sweden)

    Alexandre Lopes Lourenço

    2010-01-01

    Full Text Available Our report shows the strategies adopted by pharmaceutical industry in the development of incremental innovations, through the development carried out after the launch of omeprazole. Some improvements are really necessary and others are used only as a market strategy and evergreening.

  18. Safety and feasibility of long-term intravenous sodium nitrite infusion in healthy volunteers.

    Directory of Open Access Journals (Sweden)

    Ryszard M Pluta

    Full Text Available BACKGROUND: Infusion of sodium nitrite could provide sustained therapeutic concentrations of nitric oxide (NO for the treatment of a variety of vascular disorders. The study was developed to determine the safety and feasibility of prolonged sodium nitrite infusion. METHODOLOGY: Healthy volunteers, aged 21 to 60 years old, were candidates for the study performed at the National Institutes of Health (NIH; protocol 05-N-0075 between July 2007 and August 2008. All subjects provided written consent to participate. Twelve subjects (5 males, 7 females; mean age, 38.8±9.2 years (range, 21-56 years were intravenously infused with increasing doses of sodium nitrite for 48 hours (starting dose at 4.2 µg/kg/hr; maximal dose of 533.8 µg/kg/hr. Clinical, physiologic and laboratory data before, during and after infusion were analyzed. FINDINGS: The maximal tolerated dose for intravenous infusion of sodium nitrite was 267 µg/kg/hr. Dose limiting toxicity occurred at 446 µg/kg/hr. Toxicity included a transient asymptomatic decrease of mean arterial blood pressure (more than 15 mmHg and/or an asymptomatic increase of methemoglobin level above 5%. Nitrite, nitrate, S-nitrosothiols concentrations in plasma and whole blood increased in all subjects and returned to preinfusion baseline values within 12 hours after cessation of the infusion. The mean half-life of nitrite estimated at maximal tolerated dose was 45.3 minutes for plasma and 51.4 minutes for whole blood. CONCLUSION: Sodium nitrite can be safely infused intravenously at defined concentrations for prolonged intervals. These results should be valuable for developing studies to investigate new NO treatment paradigms for a variety of clinical disorders, including cerebral vasospasm after subarachnoid hemorrhage, and ischemia of the heart, liver, kidney and brain, as well as organ transplants, blood-brain barrier modulation and pulmonary hypertension. CLINICAL TRIAL REGISTRATION INFORMATION: http

  19. Venous plasma levels of endothelin-1 are not altered immediately after nitroglycerin infusion in healthy subjects

    DEFF Research Database (Denmark)

    Thomsen, L L; Iversen, Helle Klingenberg; Emmeluth, C

    1995-01-01

    before and immediately (5-30 s) after 80 min infusion of NTG (glyceryl trinitrate) or saline in 12 healthy subjects. On two different days separated by at least 1 week, NTG in four different doses, 0.015, 0.25, 1.0, and 2.0 micrograms. kg-1. min-1, or placebo (isotonic saline) was infused successively...... for 20 min each dose. During the infusion blood pressure and heart rate were measured. NTG infusion significantly decreased systolic blood pressure from 112.4 to 103.4 mmHg and pulse pressure from 39.3 to 29.5 mmHg. Heart rate increased from 62.7 to 73.1 beats. min-1. No changes in endothelin-1 plasma...... levels were induced by NTG infusion (2.4 pg.ml-1 before NTG vs. 2.7 pg.ml-1 after NTG) and placebo infusion also did not affect plasma endothelin-1. It is concluded that venous plasma levels of endothelin-1 are not altered immediately after NTG infusion....

  20. Propylene glycol accumulation in critically ill patients receiving continuous intravenous lorazepam infusions.

    Science.gov (United States)

    Horinek, Erica L; Kiser, Tyree H; Fish, Douglas N; MacLaren, Robert

    2009-12-01

    Lorazepam is recommended by the Society of Critical Care Medicine as the preferred agent for sedation of critically ill patients. Intravenous lorazepam contains propylene glycol, which has been associated with toxicity when high doses of lorazepam are administered. To evaluate the accumulation of propylene glycol in critically ill patients receiving lorazepam by continuous infusion and determine factors associated with propylene glycol concentration. A 6-month, retrospective, safety assessment was conducted of adults admitted to the medical intensive care unit who were receiving lorazepam by continuous infusion for 12 hours or more. Propylene glycol serum concentrations were obtained 24-48 hours after continuous-infusion lorazepam was initiated and every 3-5 days thereafter. Propylene glycol accumulation was defined as concentrations of 25 mg/dL or more. Groups with and without propylene glycol accumulation were compared and factors associated with propylene glycol concentration were determined using multivariate correlation regression analyses. Forty-eight propylene glycol serum samples were obtained from 33 patients. Fourteen (42%) patients had propylene glycol accumulation, representing 23 (48%) serum samples. Univariate analyses showed the following factors were related to propylene glycol accumulation: baseline renal dysfunction, presence of alcohol withdrawal, sex, age, Acute Physiology and Chronic Health Evaluation (APACHE II) score, rate of lorazepam continuous infusion, and 24-hour lorazepam dose. Multivariate linear regression modeling demonstrated that propylene glycol concentration was strongly associated with the continuous infusion rate and 24-hour dose (adjusted r(2) > or = 0.77; p propylene glycol concentration (r(2) > or = 0.71; p propylene glycol concentration. Seven (21%) patients developed renal dysfunction after continuous-infusion lorazepam was initiated, but associated causes were indeterminable. Other possible propylene glycol

  1. Identification of the Acid-Induced Degradation Products of Omeprazole and 5-hydroxyomeprazole by High Resolution Mass Spectrometry.

    Science.gov (United States)

    Roberts, J; McNaughtan, M; MacLachlan, J; Hunter, C; Pahl, O

    2018-03-23

    Omeprazole is used to treat gastric disorders and is one of the most commonly consumed drugs in the western world. It forms several metabolites but is mostly excreted unchanged and as 5-hydroxyomeprazole. Since omeprazole is widely prescribed, its excretion from the body has a potential environmental effect. After excretion it will enter the wastewater system and if not adequately removed during wastewater treatment will be discharged into rivers in the wastewater effluent. It is important to consider not only the parent drug but also the main metabolite (5-hydroxyomeprazole) and their degradation products to fully understand the fate of this drug during wastewater treatment. In order to do this potential degradation products need to be determined. Acid was used to artificially accelerate the degradation of omeprazole and 5-hydroxyomeprazole. A Q-Exactive Orbitrap mass spectrometer with an electrospray ion source was used to determine precursor and product ion data for the degradation products. Both starting materials quickly degrade under acidic conditions and the main degradation product formed in each case was a re-arranged monomer. Other species identified were doubly and singly charged dimers with varying numbers of sulphur atoms in the dimer bridge. Careful interpretation of the accurate mass, isotope pattern, isotope abundance and product ion spectra was used to interpret the data. The resultant degradants from omeprazole and 5-hydroxyomeprazole were analogous to each other, differing only by an oxygen atom. This investigation determined the degradation products of omeprazole and 5-hydroxyomeprazole and proposed structures based on the accurate mass and isotope information. The product ions from the degradation products are also reported. This article is protected by copyright. All rights reserved.

  2. Omeprazole versus doxycycline combination therapy with topical erythromycin the treatment of acne vulgaris: a randomized clinical trial

    Directory of Open Access Journals (Sweden)

    Fariba Jaffary

    2017-04-01

    Full Text Available Background: Acne vulgaris is self-limiting, multifactorial disease involving sebaceous glands. Omeprazole is a proton pump inhibitor with in vitro antibacterial effects against staphylococcus aureus and anti-androgen that can be potential treatment of acne vulgaris. This study was designed to evaluate the efficacy of oral omeprazole and erythromycin 4% compared to doxycycline combination therapy in the treatment of acne vulgaris. Methods: In this clinical trial study, patients with moderate acne were referred to Skin Diseases and Leishmaniasis Research Center, Isfahan University of Medical Science, Iran, during August 2014 until November 2015 and were randomized into two groups receiving topical erythromycin 4% plus omeprazole (34 patients or doxycycline (35 patients for 3 months. Moderate acne, lack of sensitivity to proton pump inhibitors, lack of warfarin, phenytoin, diazepam consumption, lack of active liver or kidney disease, being older than 12 years, were considered as inclusion criteria. Pregnant or lactating patients, patients with drug allergy history, patients taking oral contraceptives, acne topical medications (including retinoids or systemic treatment within 30 days of study, patients with oligomenorrhea, hirsutism, acne conglobata, acne fulminant or body acne alone were excluded from the study. All patients were tested for Helicobacter pylori test at the beginning of the study. Results: Both inflammatory and non-inflammatory lesions decreased in both groups with negative correlation with age (P< 0.05. There was no significant correlation between positive Helicobacter pylori test and inflammatory or non-inflammatory lesion reduction (P= 0.794, P= 0.514. Also, patient satisfaction and rate of total drug side effects was not different between two treatment groups. Rate of skin reactions was 20.58% in omeprazole treated group and 11.42% in doxycycline group. For side effects, other than skin it was 2.94% versus 14.28% respectively

  3. The Basophil Activation Test Can Be of Value for Diagnosing Immediate Allergic Reactions to Omeprazole.

    Science.gov (United States)

    Laguna, Jose J; Bogas, Gador; Salas, Maria; Mayorga, Cristobalina; Dionicio, Javier; Gonzalez-Mendiola, Rosario; Ariza, Adriana; Fernández-Santamaría, Ruben; Olazabal, Isabel; Doña, Inmaculada; Fernandez, Tahia D; Torres, Maria J

    2018-01-12

    Proton pump inhibitors (PPIs) are commonly used to treat gastrointestinal diseases. Incidence of hypersensitivity reactions to PPIs has risen, likely because of increased consumption. Their diagnosis is difficult, with skin tests (STs) presenting low sensitivity, making it necessary to perform drug provocation tests (DPTs). The value of in vitro tests for the diagnosis of immediate reaction to PPI is unclear. To analyze the diagnostic value of the basophil activation test (BAT) in a group of patients diagnosed with immediate allergy to omeprazole. The study included 42 patients with confirmed immediate allergic reactions to omeprazole confirmed by positive ST results or DPT results and 22 age- and sex-matched subjects tolerant to PPIs. BAT was performed with omeprazole, pantoprazole, and lansoprazole using CD63 and CD203c as activation markers. ST sensitivity was 66.7% with a specificity of 100%. BAT using CD63 with a stimulation index of more than 2 as positive revealed a sensitivity of 73.8%, a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 66.7%. BAT was positive in 57.1% of patients with negative ST result, and thus by combining ST and BAT we can correctly diagnose 85.7% of patients with immediate allergy to omeprazole. BAT represents a complementary tool for inclusion in the allergological workup for patients allergic to omeprazole. When combined with ST, it can be of value to guide the clinician as to whether to perform a DPT. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  4. The effect of glucagon infusion on kidney function in short-term insulin-dependent juvenile diabetics

    DEFF Research Database (Denmark)

    Parving, H H; Christiansen, J S; Noer, I

    1980-01-01

    Kidney function was studied in nine, metabolically well controlled, short-term insulin-dependent male diabetics before and during glucagon infusion of 4 to 5 and 8 to 10 ng/kg/min. Glomerular filtration rate, effective renal plasma flow (steady-state infusion technique, with urinary collections......, using 125I-iothalamate and 131I-iodohippurate), and urinary albumin and beta 2-microglobulin excretion rates were measured. The mean plasma glucagon concentration increased during infusion from 254 +/- 19 pg/ml to 440 +/- 31 pg/ml (low dose) and 730 +/- 52 pg/ml (high dose). Glomerular filtration rate...... increased in all subjects from 133 +/- 5 before the glucagon infusion to 141 +/- 4 with the low dose, and 148 +/- 7 ml/min/1.73 m2 with the high dose (p

  5. Eradication of H. pylori in a developing country: comparison of lansoprazole versus omeprazole with norfloxacin, in a dual-therapy study.

    Science.gov (United States)

    Gupta, V K; Dhar, A; Srinivasan, S; Rattan, A; Sharma, M P

    1997-07-01

    Lansoprazole, a newer benzimidazole, is more potent than omeprazole in its anti-Helicobacter pylori effect in vitro. The present study was aimed at assessing its efficacy in a developing country. Fifty patients were randomized to receive either lansoprazole or omeprazole, with norfloxacin for 2 wk; the ulcer healing rates, H. pylori eradication rates, and recurrence rates were compared over a 6-month period. Both lansoprazole and omeprazole were equally effective in inducing healing of ulcer (96.1 vs 95.5%, p > 0.05) and eradicating H. pylori (76.9 vs 63.9%, p > 0.05), with very low recurrence rates over a 6-month follow-up period. Either lansoprazole or omeprazole combined with norfloxacin is effective in eradicating H. pylori in a high percentage of cases of duodenal ulcer, with little difference between the two proton pump inhibitors.

  6. Symptomatic response to blocked and unblocked pentagastrin stimulation in functional dyspepsia - Comparison of responders and non-responders to omeprazole identified in a single-subject trial model

    DEFF Research Database (Denmark)

    Madsen, L.G.; Bytzer, P.

    2008-01-01

    hypothesized that RSD trial responders and non-responders would react differently to gastric acid stimulation. Development of epigastric pain was expected in RSD trial responders after pentagastrin stimulation during placebo treatment, but not during omeprazole treatment. In non-responders, epigastric pain...... was expected not to be influenced by gastric acid stimulation or type of treatment. Methods: Nineteen patients were evaluated. Symptomatic response to pentagastrin (6 mu g/kg) was assessed twice in each patient following placebo and omeprazole (40 mg bid) treatment in a randomized, double-blind, cross...... but not during omeprazole treatment. Results: The acid provocation test was positive in 43% (3/7) of responders compared to only 17% (2/12) non-responders. VAS-score changes showed trends towards a more pronounced symptom reduction during omeprazole treatment in responders compared to non-responders. Conclusion...

  7. Does overnight normalization of plasma glucose by insulin infusion affect assessment of glucose metabolism in Type 2 diabetes?

    DEFF Research Database (Denmark)

    Staehr, P; Højlund, Kurt; Hother-Nielsen, O

    2003-01-01

    AIMS: In order to perform euglycaemic clamp studies in Type 2 diabetic patients, plasma glucose must be reduced to normal levels. This can be done either (i) acutely during the clamp study using high-dose insulin infusion, or (ii) slowly overnight preceding the clamp study using a low-dose insulin...... infusion. We assessed whether the choice of either of these methods to obtain euglycaemia biases subsequent assessment of glucose metabolism and insulin action. METHODS: We studied seven obese Type 2 diabetic patients twice: once with (+ ON) and once without (- ON) prior overnight insulin infusion. Glucose...... turnover rates were quantified by adjusted primed-constant 3-3H-glucose infusions, and insulin action was assessed in 4-h euglycaemic, hyperinsulinaemic (40 mU m-2 min-1) clamp studies using labelled glucose infusates (Hot-GINF). RESULTS: Basal plasma glucose levels (mean +/- sd) were 5.5 +/- 0.5 and 10...

  8. Use of continuous infusion pumps during radiation treatment.

    Science.gov (United States)

    Bak, Kate; Gutierrez, Eric; Lockhart, Elizabeth; Sharpe, Michael; Green, Esther; Costa, Sarah; Hertz, Sherrie; Kaizer, Leonard; Whitton, Anthtony; Warde, Padraig

    2013-03-01

    Despite increasing chemoradiotherapy treatment, there is a paucity of information regarding the effects of radiation exposure on ambulatory infusion pumps used to deliver chemotherapy or other essential medications. The aim of this overview is to present the available evidence on this subject, heighten awareness within the clinical community, provide considerations for minimizing possible negative effects on patient care, and encourage the monitoring of infusion devices after exposure to radiation or electromagnetic interference. Published literature was systematically searched using MEDLINE and EMBASE; gray literature was searched using Google and an environmental scan of relevant Web sites. A multidisciplinary working group reviewed the compiled evidence, and a draft of the document was sent to health professionals from various disciplines for an external review. Four reports and three manufacturer device alerts were identified that suggest a risk of pump malfunction as a result of radiation exposure. The estimated cumulative dose at which pump failure has been reported ranges from 28.5 to 42 Gy; however, additional clinical investigations should be undertaken. Pump relocation, pump shielding, and assessment of the pump after radiation exposure are most commonly suggested to minimize pump malfunction related to radiation exposure. A list of additional considerations is offered for those developing institution specific policies and procedures based on the available evidence and expert consensus. The varied and unpredictable results of radiation exposure on infusion devices suggest that additional testing should be carried out to determine the limits of dose exposure and to raise awareness around this patient safety issue.

  9. A comparison of continuous infusion of vecuronium and atracurium in midline and paramedian laparotomies.

    Directory of Open Access Journals (Sweden)

    Chaudhari L

    1999-01-01

    Full Text Available This was a study to compare continuous intravenous infusion of atracurium with continuous intravenous infusion of vecuronium for intraoperative muscle relaxation in 62 ASA I / II patients. Scheduled for laparotomies and pelvic surgeries under general anaesthesia. They were randomly allocated in two groups to receive either vecuronium infusion of 50 microg/kg/hour following a bolus dose of 0.1 microg/kg, or atracurium infusion of 400 microg/kg/hour following a bolus dose of 0.5 microg/kg. The mean infusion dose of atracurium was 478 +/- 44.11 microg/kg/hour and that of vecuronium was 63.2 +/- 74 microg/kg/hour for adequate muscle relaxation. The depth of neuromuscular blockade was monitored by using peripheral nerve stimulator so that only one twitch of train of four was present, resistance to ventilation, surgical relaxation and haemodynamic changes. Vecuronium infusions produced more haemodynamic stability than atracurium infusions. Vecuronium produced lesser change in systolic blood pressure (mean change of 3. 46 +/- 3.33% from baseline values as compared to atracurium (mean change of 5.81 +/- 3.73% from baseline values ( p < 0.01 which was statistically significant. The difference in mean pulse rate change from baseline value in the atracurium group (4.78 +/- 2.745% was less than that in the vecuronium group (5.99 +/- 2.67%, which was not statistically significant. Spontaneous recovery was faster with vecuronium (540.94 +/- 76.46 seconds as compared to atracurium (596. 33 +/- 72.48 seconds. 84.4% of patients who received vecuronium fell within good to very good category of muscle relaxation as compared to 63.3% in atracurium group. There were no cost benefits when either agents were used in infusion form.

  10. Comparison of intermittent versus continuous vancomycin infusion for the treatment of late-onset sepsis in preterm infants.

    Science.gov (United States)

    Demirel, B; İmamoglu, E; Gursoy, T; Demirel, U; Topçuoglu, S; Karatekin, G; Ovali, F

    2015-01-01

    Vancomycin a frequently used antimicrobial for the treatment of late-onset neonatal sepsis. It can be infused either intermittently or continuously, however, there is no consensus on the optimal dosing regimen. To evaluate microbiological outcomes, clinical response and adverse events of vancomycin when administered via continuos intravenous infusion. The files of preterm infants (improvement rates, Töllner scores and microbiological outcomes did not differ significantly between groups. At 48th hour of vancomycin infusion, 52.8% of infants achieved therapeutic concentrations of vancomycin in group II compared with 34.1% of patients in group I (p = 0.002). Thirty-nine percent of infants in group I had supratherapeutic concentrations of vancomycin at 48th hour compared with 5.6% in group II (p = 0.002). Dose adjustment rate in group I did not differ than group II (65.9% vs. 52.8% respectively, p = 0.3). However, when we subdivide group I into two according to dosing intervals, dose adjustment rates were more common in infants with a gestational age <29 weeks for whom intermittent infusion was performed in 18 hours intervals (92.9% vs 51.9% , p = 0.014). In preterm infants, continuous and intermittent infusions of vancomycin have similar clinical efficacies. Continuous infusion is well-tolerated and require less blood sampling compared to intermittent infusion especially in infants less than 29 weeks of gestational age.

  11. Potentiation of the action of metronidazole on Helicobacter pylori by omeprazole and bismuth subcitrate

    DEFF Research Database (Denmark)

    Andersen, L P; Colding, H; Kristiansen, J E

    2000-01-01

    test (Etest). With 0.5 MIC of either of the two drugs, the susceptibility of all H. pylori4 mg/l) reverted to being metronidazole sensitive. These results suggested that either bismuth salts or proton pump inhibitors may be effective in the treatment of some infections with metronidazole-resistant H...... to regimens that include proton pump inhibitors. In the present study, the synergistic effect of subinhibitory concentrations (0.25-0.5 MIC) of either bismuth subcitrate or omeprazole with metronidazole on the susceptibility of 42 H. pylori strains was investigated by agar dilution method and the Epsilometer......Treatment failures using triple therapy that include metronidazole, are common in patients infected with metronidazole-resistant Helicobacter pylori in the gastric mucosa. Higher eradication rates in such patients have been described when treatment regimens include bismuth salts compared...

  12. Oral esomeprazole vs injectable omeprazole for the prevention of hemorrhage after endoscopic submucosal dissection.

    Science.gov (United States)

    Uchiyama, Takashi; Higurashi, Takuma; Kuriyama, Hitoshi; Kondo, Yoshinobu; Hata, Yasuo; Nakajima, Atsushi

    2017-10-16

    To evaluate the effectiveness of oral esomeprazole (EPZ) vs injectable omeprazole (OPZ) therapy to prevent hemorrhage after endoscopic submucosal dissection (ESD). A case-control study was conducted using a quasi-randomized analysis with propensity score matching. A total of 258 patients were enrolled in this study. Patients were treated with either oral EPZ or injectable OPZ. The endpoint was the incidence of hemorrhage after ESD. Data of 71 subjects treated with oral EPZ and 172 subjects treated with injectable OPZ were analyzed. Analysis of 65 matched samples revealed no difference in the incidence of hemorrhage after ESD between the oral EPZ and injectable OPZ groups (OR = 0.89, 95%CI: 0.35-2.27, P ≥ 0.99). We conclude that oral EPZ therapy is a useful alternative to injectable PPI therapy for the prevention of hemorrhage after ESD.

  13. Development of a multiparticulate system containing enteric-release mini-tablets of omeprazole

    Directory of Open Access Journals (Sweden)

    Volnei Jose Tondo Filho

    2014-09-01

    Full Text Available The main aim of this study was to develop a multiparticulate system containing mini-tablets of omeprazole formulated with an enteric polymer with pH-dependent solubility. Pre-formulation studies showed good flow and compaction capacity, leading to the production ofhigh quality mini-tablets. The mini-tablets were coated in a fluidized bed with hydroxypropylmethylcellulose /Eudragit(r L30D55 and packed into hard gelatin capsules. The dissolution profile showed gastro-resistance and zero-order kinetics. The dissolution profile for the formulation containing lactose as the diluent and coated with 12% (tablet weight gain of polymer was similar to that ofthe reference drug.

  14. Validated spectrophotometric methods for simultaneous determination of Omeprazole, Tinidazole and Doxycycline in their ternary mixture

    Science.gov (United States)

    Lotfy, Hayam M.; Hegazy, Maha A.; Mowaka, Shereen; Mohamed, Ekram Hany

    2016-01-01

    A comparative study of smart spectrophotometric techniques for the simultaneous determination of Omeprazole (OMP), Tinidazole (TIN) and Doxycycline (DOX) without prior separation steps is developed. These techniques consist of several consecutive steps utilizing zero/or ratio/or derivative spectra. The proposed techniques adopt nine simple different methods, namely direct spectrophotometry, dual wavelength, first derivative-zero crossing, amplitude factor, spectrum subtraction, ratio subtraction, derivative ratio-zero crossing, constant center, and successive derivative ratio method. The calibration graphs are linear over the concentration range of 1-20 μg/mL, 5-40 μg/mL and 2-30 μg/mL for OMP, TIN and DOX, respectively. These methods are tested by analyzing synthetic mixtures of the above drugs and successfully applied to commercial pharmaceutical preparation. The methods that are validated according to the ICH guidelines, accuracy, precision, and repeatability, were found to be within the acceptable limits.

  15. Micrometer size rod formed by secondary self assembly of omeprazole with α- and β-cyclodextrins

    Science.gov (United States)

    Rajendiran, N.; Venkatesh, G.

    2015-02-01

    Self assembly of α-cyclodextrin (α-CD) and β-cyclodextrin (β-CD) micro rods induced by omeprazole (OMP) were observed by SEM and TEM. OMP/CD inclusion complexes have formed the secondary self assembly micro meter size rod like structure. This structure was driven by the intermolecular hydrogen bonding as well as van der Waals forces. Both forces induced the ordered assembly and arrangement of OMP/CD inclusion complexes, whereas CD molecules acted as molecular bricks. The OMP/CD inclusion complexes primary assembled form individual nanorods and then secondary self aggregate nanorods were form a micro meter rod structure. The results indicate that inter-nanotubular hydrogen bonding plays a crucial role in the formation of the self assembled micro rods. The inclusion complexes were also characterized using FT-IR, DSC, powder XRD, 1H NMR, absorption, fluorescence, life time measurements and molecular modeling methods.

  16. Improved Diabetes Control and Pancreatic Function in a Type 2 Diabetic after Omeprazole Administration

    Directory of Open Access Journals (Sweden)

    I. N. Mefford

    2012-01-01

    Full Text Available A 43-year-old man with type 2 diabetes, opposed to insulin use and poorly responsive to oral agents added sequentially over 6 years, was placed on 40 mg omeprazole twice daily. A linear decline in daily fasting blood glucose was observed over the first two-month treatment, and his hemoglobin A1c was reduced from 11.9% to 8.2%, then sustained at 8.1% after four months. Glucose, insulin, and C-peptide response to a 2-hour glucose tolerance test were consistently improved across this time period, and calculated beta-cell mass increased by 67%. We believe these responses are consistent with activation or neogenesis of pancreatic beta cells, possibly through a gastrin-mediated mechanism.

  17. Potentiation of the action of metronidazole on Helicobacter pylori by omeprazole and bismuth subcitrate

    DEFF Research Database (Denmark)

    Andersen, L P; Colding, H; Kristiansen, J E

    2000-01-01

    Treatment failures using triple therapy that include metronidazole, are common in patients infected with metronidazole-resistant Helicobacter pylori in the gastric mucosa. Higher eradication rates in such patients have been described when treatment regimens include bismuth salts compared...... to regimens that include proton pump inhibitors. In the present study, the synergistic effect of subinhibitory concentrations (0.25-0.5 MIC) of either bismuth subcitrate or omeprazole with metronidazole on the susceptibility of 42 H. pylori strains was investigated by agar dilution method and the Epsilometer...... test (Etest). With 0.5 MIC of either of the two drugs, the susceptibility of all H. pylori4 mg/l) reverted to being metronidazole sensitive. These results suggested that either bismuth salts or proton pump inhibitors may be effective in the treatment of some infections with metronidazole-resistant H...

  18. Pharmacokinetic and pharmacodynamic effects of two omeprazole formulations on stomach pH and gastric ulcer scores.

    Science.gov (United States)

    Raidal, S L; Andrews, F M; Nielsen, S G; Trope, G

    2017-11-01

    Limited data are available on the relative pharmacokinetics and pharmacodynamics of different omeprazole formulations. To compare pharmacokinetic and pharmacodynamic effects of a novel omeprazole formulation against a currently registered product. Masked 2 period, 2 treatment crossover. Twelve clinically healthy horses were studied over two 6-day treatment periods. Horses were randomly assigned to receive a novel omeprazole paste (Ulcershield: ULS) or a currently registered reference omeprazole product (OMO). Gastric pH was measured continuously for 10 h on the day prior to commencing treatment (Day -1) and after 6 days of oral treatment (Day 5) using in situ antimony pH probes within an indwelling nasogastric tube. Plasma pharmacokinetics were determined on Days 0 and 6. Treatment significantly (P<0.005) increased gastric pH on Day 5, compared to results obtained prior to treatment (Day -1) and there was no significant difference between products (P = 0.773). Similarly, comparison of median hourly gastric pH (P = 0.593), mean gastric pH (P = 0.154), percentage time pH<4 (P = 0.259) and area under the time-gastric pH response curve (P = 0.734) did not discriminate between products. Both treatments resulted in significantly lower gastric ulcer severity scores (both P = 0.004), with no difference between treatments (P = 0.688). Comparison of mean log area under time-plasma concentration curves demonstrated that, although the lower limit of the 90% confidence interval was within the -20% limit for bioequivalence, the upper limit was exceeded, suggesting that the test product could have greater bioavailability than the reference product. The small sample size, large interhorse plasma omeprazole concentrations, and low bioavailability of omeprazole impacted the sensitivity of the bioequivalence analysis. ULS matched or slightly exceeded OMO plasma concentrations. Both products resulted in equivalent increases in gastric pH, gastric pH profiles and decrease in gastric

  19. Value of infusion-DSA (Digital Subtraction Angiography) in diagnosis of primary hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Kwon, Jeong Mi; Kim, So Sun; Huh, Jin Do; Kim, Ho Joon; Chun, Byung Hee; Joh, Young Duk

    1991-01-01

    In order to evaluate diagnostic effectiveness of the infusion-study, the authors prospectively evaluated hepatic digital subtraction angiography of bolus and infusion studies in 71 patients with hepatocellular carcinoma. In contrast to Bolus-DSA, which involves a 2 second injection of 10cc of contrast medium, the Infusion-DSA uses a protracted (10sec) injection, a lower injection rate, and larger total dose of contrast medium (20cc). The information yield of arterial and capillary phases of Infusion-DSA was compared with that of Bolus-DSA and graded as 'improved(+)', 'equivalent( ± )', or 'poor(-)'. Also, the contribution of Infusion-DSA to the diagnosis was classified into one of five in a graded system. In 29 hepatocellular patients, the Infusion-DSA was helpful in detecting daughter nodules, fibrous capsule and arteriovenous shunt. Infusion-DSA is a useful complementary technique in the diagnosis of hepatocellular carcinoma and was also helpful in determining the selection of the therapeutic modality of hepatocellular carcinoma

  20. Short-time, high-dosage penicillin infusion therapy of syphilis

    DEFF Research Database (Denmark)

    Lomholt, Hans; Poulsen, Asmus; Brandrup, Flemming

    2003-01-01

    The optimal dosage and duration of penicillin treatment for the various stages of syphilis are not known. We present data on 20 patients with syphilis (primary, secondary or latent) treated with high-dose, short-time penicillin infusion therapy. Patients were given 10 MIU of penicillin G intraven......The optimal dosage and duration of penicillin treatment for the various stages of syphilis are not known. We present data on 20 patients with syphilis (primary, secondary or latent) treated with high-dose, short-time penicillin infusion therapy. Patients were given 10 MIU of penicillin G...

  1. Enantioselective endocrine disrupting effects of omeprazole studied in the H295R cell assay and by molecular modeling

    DEFF Research Database (Denmark)

    Sørensen, Amalie Møller; Hansen, Cecilie Hurup; Bonomo, Silvia

    2016-01-01

    -OME) and R-omeprazole (R-OME) in CYP17A1, CYP19A1 and CYP21A2 were carried out. Exposing H295R cells to OME and its enantiomers resulted in an increase of progesterone (PRO) and 17α-hydroxy-progesterone (OH-PRO) levels. At the same time, a decrease in the corticosteroid and androgen synthesis was observed...... of the heme for S-OME in CYP17A1 and S- and R-OME in CYP21A2. However, density functional theory calculations suggest that the direct N-Fe interaction is weak. The study demonstrates enantioselective differences in the endocrine disrupting potential of chiral drugs such as omeprazole. These findings may have...

  2. Pantoprazole before Endoscopy in Patients with Gastroduodenal Ulcer Bleeding: Does the duration of Infusion and Ulcer Location Influence the Effects?

    Directory of Open Access Journals (Sweden)

    Istvan Rácz

    2012-01-01

    Full Text Available The aim of this study was to investigate the effect of preemptive pantoprazole infusion on early endoscopic findings in patients with acute ulcer bleeding. Records of 333 patients admitted with acute ulcer bleeding were analyzed. Ulcer bleeders were given either 80 mg bolus of pantoprazole followed by continuous infusion of 8 mg per hour or saline infusion until endoscopy. In 93 patients saline infusion whereas in 240 patients bolus plus infusion of pantoprazole was administrated with mean (±SD durations of 5.45±12.9 hours and 6.9±13.2 hours, respectively (P=0.29. Actively bleeding ulcers were detected in 46/240 (19.2% of cases in the pantoprazole group as compared with 23/93 (24.7% in the saline infusion group (P=0.26. Different durations of pantoprazole infusion (0–4 hours, >4 hours, and >6 hours had no significant effect on endoscopic and clinical outcome parameters in duodenal ulcer bleeders. Gastric ulcer bleeders on pantoprazole infusion longer than 4 and 6 hours before endoscopy had actively bleeding ulcers in 4.3% and 5% compared to the 19.5% active bleeding rate in the saline group (P=0.02 and P=0.04. Preemptive infusion of high-dose pantoprazole longer than 4 hours before endoscopy decreased the ratio of active bleeding only in gastric but not in duodenal ulcer patients.

  3. Einfluss von Thujonen und Omeprazol auf die Aktivität der glatten Muskelzelle im Ileum der Ratte

    OpenAIRE

    Huhnstock, Stefan

    2010-01-01

    Untersucht wurde der Einfluss von Thujonen (α Thujon, αβThujon, natürliches Mischthujon) und Omeprazol auf die Ruheaktivität, den Basaltonus, die pharmakologisch vorstimulierte glatte Muskulatur ,sowie die elektrisch induzierte Kontraktionen und die elektrisch induzierte Relaxation unter nicht-adrenergen nicht-cholinergen Bedingungen an der glatten Muskelzelle im Ileum von Ratten. Auf die Ruheaktivität und den Basaltonus hatten die Substanzen keinen Einfluss. Thujone hatten einen signifikante...

  4. General-purpose infusion pumps.

    Science.gov (United States)

    1998-01-01

    General-purpose infusion pumps deliver liquid medications to patients through intravenous or epidural routes at specified flows. They are most often used in hospitals and alternative care settings (e.g., physician' offices, patients' homes) when liquid medications need to be administered with greater accuracy or at higher flows than can be provided through a manually adjusted gravity administration set. In this Update of our February 1997 Evaluation of infusion pumps (Health Devices 26[2]), we tested 3 additional pumps from 3 suppliers. We also rated and ranked them in comparison with the 16 units from the February 1997 study that are still being produced. With a few exceptions, we tested the new pumps against the same criteria and using the same test methods as those in the previous Evaluation. However, for this Update, the focus of our findings has broadened: although we continue to place strong emphasis on the pumps' protection against gravity free-flow, we also give significant weight to their overall safety, performance, and human factors design. As a result, our ratings and rankings scheme has changed, affecting the rankings of some of the previously evaluated units. Of the 19 currently available units that have been evaluated to date, we rated 13 units Acceptable, with 5 of those units ranked above the other 8. A further 5 units were rated Conditionally Acceptable; we consider them Acceptable if they are used with the available free-flow protection. And 1 unit had performance problems that caused us to rate it Unacceptable (this unit has been recalled by its supplier; see the inset on page 162). As always, we caution readers not to base selection and purchasing decisions on our conclusions alone, but on a thorough understanding of the issues behind those conclusions, which can be gained by reading this Evaluation in its entirety and carefully reviewing the February 1997 issue.

  5. Biliary amino acid and glutathione secretion in response to amino acid infusion in the isolated rat liver.

    Science.gov (United States)

    Shattuck, K E; Grinnell, C D; Rassin, D K

    1994-01-01

    The intravenous infusion of amino acid solutions has been associated with cholestatic liver injury in hospitalized patients and in laboratory animals. In the isolated rat liver, we recently showed that the acute decrease in bile flow, previously reported by other investigators, is dose related, reversible, and associated with dose-related increases in total biliary amino acid concentrations. In the present study, we characterized the effects of graded infusions of amino acid solutions, with and without taurocholate, on biliary secretion of individual amino acids and glutathione, an important regulator of bile flow. Livers from young adult male rats were perfused with an amino acid solution for 1 hour and allowed to recover for 30 minutes. Infusion of the amino acid solution was associated with dose-related increases in biliary concentrations of most amino acids included in the amino acid solution. Infusion of amino acid solutions resulted in a decreased bile/perfusate ratio of most amino acids, which were secreted into bile in amounts approximating their calculated uptake from the infusate. The inclusion of taurocholate in the infusate was associated with lower biliary concentrations of each individual amino acid and significant decreases in biliary total, reduced, and oxidized glutathione. Further investigation of the relationship between these changes in biliary amino acids and glutathione concentrations and the cholestasis associated with infusion of amino acid solutions may provide insights into the mechanism by which amino acids induce such cholestasis.

  6. Modelling the effect of continuous infusion DTPA therapy on the retention and dosimetry of inhaled actinides

    International Nuclear Information System (INIS)

    Guilmette, R.A.; Muggenburg, B.A.

    1989-01-01

    A biokinetic model of the treatment of dogs that inhaled 241 AmO 2 aerosols with continuously infused DTPA has been adapted from a previously published model by Mewhinney and Griffith. This model was parameterised to simulate both the tissue retention and the excretion of 241 Am, and was used to estimate the cumulative radiation doses to tissues at risk from the α radiation of 241 Am. The results showed that at 64 days after exposure, the liver dose of the DTPA-treated animals was 3% that of the corresponding controls, the skeleton dose was 2%, the kidney dose was 4% and the lung dose was 67% of controls. (author)

  7. Systems biology analysis of omeprazole therapy in cirrhosis demonstrates significant shifts in gut microbiota composition and function.

    Science.gov (United States)

    Bajaj, Jasmohan S; Cox, I Jane; Betrapally, Naga S; Heuman, Douglas M; Schubert, Mitchell L; Ratneswaran, Maiyuran; Hylemon, Phillip B; White, Melanie B; Daita, Kalyani; Noble, Nicole A; Sikaroodi, Masoumeh; Williams, Roger; Crossey, Mary M E; Taylor-Robinson, Simon D; Gillevet, Patrick M

    2014-11-15

    Proton pump inhibitors (PPI) have been associated with infectious complications in cirrhosis, but their impact on distal gut microbiota composition and function is unclear. We aimed to evaluate changes in stool microbiota composition and function in patients with cirrhosis and healthy controls after omeprazole therapy. Both 15 compensated cirrhotic patients and 15 age-matched controls underwent serum gastrin measurement, stool microbiota profiling with multitagged pyrosequencing, and urinary metabolic profiling with NMR spectroscopy to assess microbial cometabolites before/after a 14-day course of 40 mg/day omeprazole under constant diet conditions. Results before (pre) and after PPI were compared in both groups, compared with baseline by systems biology techniques. Adherence was >95% without changes in diet or MELD (model for end-stage liver disease) score during the study. Serum gastrin concentrations significantly increased after PPI in cirrhosis (pre 38.3 ± 35.8 vs. 115.6 ± 79.3 pg/ml P microbiota change was seen in both controls and cirrhosis after omeprazole (QIIME P microbiota shift and functional change in the distal gut in patients with compensated cirrhosis that could set the stage for bacterial overgrowth. Copyright © 2014 the American Physiological Society.

  8. Affinity capillary electrophoresis and fluorescence spectroscopy for studying enantioselective interactions between omeprazole enantiomer and human serum albumin.

    Science.gov (United States)

    Xu, Yujing; Hong, Tingting; Chen, Xueping; Ji, Yibing

    2017-05-01

    Baseline separation of omeprazole (OME) enantiomers was achieved by affinity capillary electrophoresis (ACE), using human serum albumin (HSA) as the chiral selector. The influence of several experimental variables such as HSA concentration, the type and content of organic modifiers, applied voltage and running buffer concentration on the separation was evaluated. The binding of esomeprazole (S-omeprazole, S-OME) and its R-enantiomer (R-omeprazole, R-OME) to HSA under simulated physiological conditions was studied by ACE and fluorescence spectroscopy which was considered as a reference method. ACE studies demonstrated that the binding constants of the two enantiomers and HSA were 3.18 × 10 3 M -1 and 5.36 × 10 3 M -1 , respectively. The binding properties including the fluorescence quenching mechanisms, binding constants, binding sites and the number of binding sites were obtained by fluorescence spectroscopy. Though the ACE method could not get enough data when compared with the fluorescence spectrum method, the separation and binding studies of chiral drugs could be achieved simultaneously via this method. This study is of great significance for the investigation and clinical application of chiral drugs. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Looking for the interactions between omeprazole and amoxicillin in a disordered phase. An experimental and theoretical study

    Science.gov (United States)

    Russo, Marcos G.; Sancho, Matias I.; Silva, Lorena M. A.; Baldoni, Hector A.; Venancio, Tiago; Ellena, Javier; Narda, Griselda E.

    2016-03-01

    In this paper, co-grinding mixtures of omeprazole-amoxicillin trihydrate (CGM samples) and omeprazole-anhydrous amoxicillin (CGMa samples) at 3:7, 1:1 and 7:3 molar ratios, respectively, were studied with the aim of obtaining a co-amorphous system and determining the potential intermolecular interactions. These systems were fully characterized by differential scanning calorimetry (DSC), FT-infrared spectroscopy (FTIR), X-ray powder diffraction (PXRD), scanning electron microscopy (SEM) and solid state Nuclear Magnetic Resonance (ssNMR). The co-grinding process was not useful to get a co-amorphous system but it led to obtaining the 1:1 CGMa disordered phase. Moreover, in this system both FTIR and ssNMR analysis strongly suggest intermolecular interactions between the sulfoxide group of omeprazole and the primary amine of amoxicillin anhydrous. The solubility measurements were performed in simulated gastric fluid (SGF) to prove the effect of the co-grinding process. Complementarily, we carried out density functional theory calculations (DFT) followed by quantum theory of atoms in molecules (QTAIM) and natural bond orbital (NBO) analyses in order to shed some light on the principles that guide the possible formation of heterodimers at the molecular level, which are supported by spectroscopic experimental findings.

  10. The History of Target-Controlled Infusion

    NARCIS (Netherlands)

    Struys, Michel M. R. F.; De Smet, Tom; Glen, John (Iain) B.; Vereecke, Hugo E. M.; Absalom, Anthony R.; Schnider, Thomas W.

    Target-controlled infusion (TCI) is a technique of infusing IV drugs to achieve a user-defined predicted (target) drug concentration in a specific body compartment or tissue of interest. In this review, we describe the pharmacokinetic principles of TCI, the development of TCI systems, and technical

  11. The Infusion Approach to Teacher Development.

    Science.gov (United States)

    Kowalski, Ellen M.

    1995-01-01

    The underlying premise of infusion is that information about individuals with disabilities must be more systematically integrated throughout an entire curriculum. This article describes the infusion approach to teacher development, explaining three central premises, providing sample program applications for each premise, and discussing brain…

  12. Reassessment of primed constant-infusion tracer method to measure urea kinetics

    International Nuclear Information System (INIS)

    Jahoor, F.; Wolfe, R.R.

    1987-01-01

    The validity of the primed constant-infusion tracer technique to make short-term measurements of urea production rates (R/sub a/) in humans in a physiological steady state and during disruption of steady state was evaluated. Four subjects received a primed constant infusion (P/I = 560 min) of [ 13 C]urea for 8 h. A plateau in urea enrichment was reached after 2 h and maintained throughout. When [ 13 C]- and [ 18 O]urea were simultaneously infused into four subjects at P/I ratios of 560:1 and 360:1, respectively, both tracers reached plateau enrichment at the same time (2-4 h). The enrichment at plateau was a function of the infusion rate rather than the priming dose, and calculated urea R/sub a/ was the same with either prime. In five additional experiments the technique responded acutely to a physiological perturbation (alanine infusion) in a dose-dependent manner. The results confirm that this technique is appropriate for short-term measurements of urea R/sub a/, and the requirement for accuracy in estimating the priming dose is not impractically stringent

  13. Modeling the effect of continuous infusion DTPA therapy on the retention and dosimetry of inhaled actinides

    International Nuclear Information System (INIS)

    Guilmette, R.A.; Muggenburg, B.A.

    1988-01-01

    A biokinetic model of the treatment of dogs that inhaled 241 AmO 2 aerosols with continuously infused DTPA has been adapted from a model previously published by Mewhinney and Griffith. This model simulated both the tissue retention and excretion of 241 Am, and was used to estimate the cumulative radiation doses to tissues at risk from 241 Am alpha radiation. The results showed that at 64 days after exposure, the liver dose of the DTPA-treated animals was 3% that of the corresponding controls, the skeletal dose was 2%, the kidney dose was 4%, and the lung dose was 67% of controls. This paper describes a biokinetic and dosimetric model that was adapted from a previously published model. It was developed to provide a means of estimating radiation doses for cases where continuously infused DTPA therapy is used to reduce radiation dose. The model was formulated for the case of 241 Am0 2 inhalation, a physicochemical form of Am that is moderately soluble in vivo, and one to which people have been exposed. Because adequate human data, particularly tissue data, are not available from cases of accidental human exposure to 241 Am, two published data sets from experiments in which Beagle dogs inhaled 241 Am0 2 aerosols have been used to obtain parameter estimates for the model. The model simulations were then used to provide dose estimates with and without infused-DTPA therapy. (author)

  14. Propylene Glycol-Related Delirium After Esmolol Infusion.

    Science.gov (United States)

    Kapitein, Berber S; Biesmans, Renee S C G; van der Sijs, Heleen S I; de Wildt, Saskia S N

    2014-07-01

    Excipients used in oral or intravenous preparations may cause serious adverse events. We present the case of a 15-year-old boy with hypertrophic cardiomyopathy. In the pediatric intensive care unit, he received high doses of continuous intravenous esmolol (range = 20-400 µg/kg/min) for cardiac rhythm control. After a few days he developed a delirium not responding to high doses of antipsychotics or discontinuation of benzodiazepines. We eventually realized that the IV esmolol formulation contained high doses of propylene glycol and ethanol, which may accumulate after prolonged infusion and cause intoxication. Intoxication with propylene glycolcan cause neuropsychiatric symptoms. The boy's propylene glycol plasma concentration was approximately 4 g/L, whereas clinical symptoms arise at concentrations above 1 to 1.44 g/L. Application of the Naranjo adverse drug reaction probability scale suggested a probable relationship (score 6) between the propylene glycol infusion and the delirium. After discontinuation of esmolol, the delirium disappeared spontaneously. This is the first case describing excipient toxicity of esmolol, with an objective causality assessment revealing a probable relationship for the adverse event-namely, delirium-and esmolol. Although excipient toxicity is a well-known adverse drug reaction, this case stresses the importance for easily available information for and education of physicians. © The Author(s) 2014.

  15. Continuous infusion pentobarbital for refractory status epilepticus in children.

    Science.gov (United States)

    Barberio, Michael; Reiter, Pamela D; Kaufman, Jon; Knupp, Kelly; Dobyns, Emily L

    2012-06-01

    The purpose of this retrospective medical chart review was to describe dosing regimens and outcomes in children who received continuous pentobarbital therapy for refractory status epilepticus. Thirty patients (age = 6.5 ± 5.1 years; 67% male) received a mean loading dose of 5.4 ± 2.8 mg/kg with an initial infusion of 1.1 ± 0.4 mg/kg/h. Maximum infusion dose was 4.8 ± 2 mg/kg/h. Thirty-three percent of patients achieved sustained burst suppression without relapse; 66.7% experienced relapse, but 60% of those (n = 12) eventually reachieved burst suppression. Children achieving burst suppression within 24 hours of pentobarbital initiation and those older than age 5 years were 1.5 times more likely to have a positive outcome. None of these variables, however, achieved significance (Fisher exact test). Ninety-three percent of patients required inotropes; 66% acquired an infection; 10% had metabolic acidosis; and 10% experienced pancreatitis. Poor outcomes (death, encephalopathy) were observed in 33% of patients.

  16. Intravenous drugs infusion safety through smart pumps

    Directory of Open Access Journals (Sweden)

    C. Gómez-Baraza

    2014-07-01

    Full Text Available Objective: To analyze the role of smart infusion pumps in reducing errors related with the administration of intravenous medications. Method: Retrospective, observational study analyzing the implementation of a system with smart intravenous infusion pumps (Hospira MedNetTM and the role of the safety system for the detection of errors during the administration of drugs, sera, and blood. We included infusions administered at the day-care hospitals of hematology, oncology, rheumatology, and oncopediatrics. We analyzed adherence to the safety system, the number of programming errors detected, the commonly implicated drugs in these errors, and improvement actions. Results: During the study period, 120 smart pumps were implemented and data on 70,028 infusions were gathered. The rate of adherence to the safety program was 62.30% in hematology (6,887 infusions, 60,30% in oncology (28,127 infusions, 46,50% in rheumatology (1,950 infusions and 1.8% in oncopediatrics (139 infusions. 3,481 out of the established limits programming alerts were generated by the pumps: 2,716 of relative limit and 765 of absolute limit. En 807 infusions (2.17%, errors that could have had consequences for the patients could be prevented. These findings allowed implementing a series of strategies aimed at minimizing these errors in the future. Conclusions: The Hospira MedNetTM system detects deviations from the established protocols of intravenous infusion, preventing in this way potential adverse events for the patients. It also allows establishing correction measures and implementing the improvement strategies.

  17. Filling a niche market: administering drugs by injection or infusion.

    Science.gov (United States)

    Kaldy, Joanne

    2015-05-01

    There is greater incentive than ever to keep individuals requiring injectable or infusion therapy in the nursing facility-and not transfer them to a hospital-to receive those services. There is a demand for pharmacists with the skills, knowledge, and training to provide these services. To make that possible, pharmacies and pharmacists with the proper equipment, supplies, knowledge, training, and expertise are needed to work closely with physicians and nurses to provide sterile, properly compounded products and ensure that drugs are administered appropriately and in the right doses. These pharmacists also can work with facilities and practitioners to assess, improve, and document quality.

  18. Potentiation of the action of calcium hydroxide on Enterococcus faecalis by proton pump inhibitor omeprazole = Potencialização da ação do hidróxido de cálcio sobre o Enterococcus faecalis pelo inibidor da bomba de prótons omeprazol

    Directory of Open Access Journals (Sweden)

    Cogo, Deborah Meirelles

    2015-01-01

    Full Text Available Objetivo: O hidróxido de cálcio não representa uma estratégia totalmente eficaz contra Enterococcus faecalis (E. faecalis, uma bactéria anaeróbia facultativa resistente aos processos de desinfecção mais convencionais. O objetivo deste estudo in vitro foi avaliar o efeito do hidróxido de cálcio, do omeprazol e das associações destas substâncias contra Enterococcus faecalis, assim como avaliar se a catalização ácida do omeprazol pode ter influência sobre os resultados. Métodos: A Concentração Inibitória Mínima (CIM destes medicamentos contra E. faecalis (ATCC 29212 foi determinada pelo teste de macrodiluição adaptado do CLSI (Clinical Laboratory Standards Institute. Soluções com diferentes concentrações de hidróxido de cálcio, associadas ou não ao omeprazol, foram testadas. Os dados foram analisados estatisticamente pelo teste ANOVA com post-hoc de Tukey, com um nível de significância de 5%. Resultados: A CIM para o hidróxido de cálcio foi de 32 mg mL-1 e, quando associada com omeprazol, foi reduzida para 16 mg mL-1. O omeprazol e o omeprazol acidificado tiveram atividade semelhante. Conclusões: O omeprazol foi capaz de potencializar o efeito do hidróxido de cálcio, uma vez que a associação dessas drogas reduziu a CIM para o E. faecalis. A acidificação do omeprazol, quando associado com o hidróxido de cálcio, em concentrações diferentes, não influenciou o seu efeito

  19. Strontium-rubidium infusion pump with in-line dosimetry

    International Nuclear Information System (INIS)

    Barker, S.L.; Loberg, M.D.

    1986-01-01

    A strontium-rubidium infusion system is described which consists of: (a) means for generating rubidium 82 in a solution which can be infused into a patient; (b) means for infusing the solution into a patient; (c) means for measuring the radioactivity present in the solution as it is infused into the patient; and (d) means for controlling the means for infusing in response to the amount of radioactivity which has been infused into the patient

  20. The effect of glucagon on infusion cholangiography

    International Nuclear Information System (INIS)

    Evans, A.F.; Whitehouse, G.H.

    1979-01-01

    An assessment has been made of the effects of glucagon on biliary tract opacification during intravenous cholangiography. Two series of infusion cholangiograms were obtained at two investigating centres designated A and B. In series A, 41 patients had ioglycamide infusions at a rate of 0.2833 g min -1 over 1 h. In series B, 31 patients had ioglycamide infusions at a rate of 0.3886 g min -1 over 30 min. Radiographs were taken in both series immediately at the end of the infusion, 10 min later and 30 min after the infusion. Two mg of intravenous glucagon was injected into alternate cases in both series A and B immediately after the first radiograph was taken at the completion of the ioglycamide infusion. Two observers in each series then assessed the radiographic opacification of the biliary system without prior knowledge of which patients had received the glucagon. Delineation of the biliary system was considered better in both series in those patients who received glucagon when compared with the controls. Gallbladder opacification was definitely increased in series A in those receiving glucagon, and a similar tendency was shown in series B. The amount of contrast in the upper intestine was increased in series A in the glucagon group, but not in series B. It is concluded that glucagon improves visualisation of the biliary tract, especially the gallbladder at infusion cholangiography. (author)

  1. Pharmacokinetics and toxicology of continuously infused nitroimidazoles

    International Nuclear Information System (INIS)

    Eifel, P.J.; Brown, J.M.

    1984-01-01

    The pharmacokinetics and toxicology of misonidazole (MISO) and SR-2508 given by continuous intraperitoneal infusion were studied in female C 3 H mice. The survival (time to death) of animals receiving continuous infusions of SR-2508 and MISO was compared and related to plasma concentration, rate of infusion and total amount of drug delivered. Brain and plasma concentrations were determined by HPLC. For SR-2508, plasma concentration was directly proportional to the infusion rate. However, as the infusion rate of MISO was doubled, the plasma concentration of MISO increased approximately 6-fold, reflecting a substantial increase in the apparent half-life. The brain/plasma concentration ratio in animals infused for up to 6 days with SR-2508 remained constant, at approximately 0.09. At plasma concentrations of 0.08-1.5 mM, animals receiving SR-2508 survived approximately 3 times as long as animals exposed to a comparable plasma concentration of MISO. Even at the lowest infusion rates employed in this study, the survival of mice receiving SR-2508 was much shorter than would have been predicted if the toxicity of these two drugs were solely related to the integral brain exposure. The low brain/plasma concentration ratio of SR-2508 was maintained throughout long continuous exposures

  2. Infliximab-Related Infusion Reactions: Systematic Review

    Science.gov (United States)

    Ron, Yulia; Kivity, Shmuel; Ben-Horin, Shomron; Israeli, Eran; Fraser, Gerald M.; Dotan, Iris; Chowers, Yehuda; Confino-Cohen, Ronit; Weiss, Batia

    2015-01-01

    Objective: Administration of infliximab is associated with a well-recognised risk of infusion reactions. Lack of a mechanism-based rationale for their prevention, and absence of adequate and well-controlled studies, has led to the use of diverse empirical administration protocols. The aim of this study is to perform a systematic review of the evidence behind the strategies for preventing infusion reactions to infliximab, and for controlling the reactions once they occur. Methods: We conducted extensive search of electronic databases of MEDLINE [PubMed] for reports that communicate various aspects of infusion reactions to infliximab in IBD patients. Results: We examined full texts of 105 potentially eligible articles. No randomised controlled trials that pre-defined infusion reaction as a primary outcome were found. Three RCTs evaluated infusion reactions as a secondary outcome; another four RCTs included infusion reactions in the safety evaluation analysis; and 62 additional studies focused on various aspects of mechanism/s, risk, primary and secondary preventive measures, and management algorithms. Seven studies were added by a manual search of reference lists of the relevant articles. A total of 76 original studies were included in quantitative analysis of the existing strategies. Conclusions: There is still paucity of systematic and controlled data on the risk, prevention, and management of infusion reactions to infliximab. We present working algorithms based on systematic and extensive review of the available data. More randomised controlled trials are needed in order to investigate the efficacy of the proposed preventive and management algorithms. PMID:26092578

  3. Phase I and pharmacologic study of 72-hour infused 5-fluorouracil and hyperfractionated cyclical radiation

    International Nuclear Information System (INIS)

    Byfield, J.E.; Frankel, S.S.; Sharp, T.R.; Hornbeck, C.L.; Callipari, F.B.

    1985-01-01

    The authors have studied 21 patients infused for 72 hours with 5- Fluorouracil (5-FU) at progressive doses combined with hyperfractionated radiation. The schedule was chosen as being one capable of inducing 5-FU radiosensitization (RS). All patients were started at a daily 5-FU dose of 40 mg/kg/24 hours; doses were then escalated with each subsequent treatment cycle to limiting toxicity or until taken off study. Patients received between one and six infusion cycles. Every treatment cycle included coincident hyperfractionated radiation to various body areas including the abdomen, chest, and head and neck region. Radiation fractionation was invariant; 1,000 rad were delivered in four equal fractions. Two fractions of 250 rad each were given on days 1 and 2 of each three day 5-FU cycle, i.e. at approximately 0, 8, 24, and 32 hours into the drug infusion. Patients were followed for toxicity; serum 5-FU concentrations were determined using a high pressure liquid chromatographic assay. 5-FU clearances were calculated from the mean serum drug levels and the infused drug dose. The toxicity spectrum was not found to be significantly different from infused drug alone in this dose range except when the head and neck region received coincident irradiation. In that region the two anticipated toxicities combined in what appears to be a synergistic fashion to enhance mucositis. Most toxicities including gastrointestinal and bone marrow appeared dependent on the mean serum 5-FU level as did mucositis itself. 5-FU clearance was found to be non-linear in this dose region but did not appear influenced by radiation to any part of the body

  4. Gastroesophageal Reflux Disease Relief in Patients Treated with Rabeprazole 20 mg versus Omeprazole 20 mg: A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    X. M. Xia

    2013-01-01

    Full Text Available Background. Randomized controlled trials (RCTs have been conducted comparing the efficacy of rabeprazole 20 mg or omeprazole 20 mg once daily for patients with erosive gastroesophageal reflux disease (GERD. Until now, no study has synthesized all available data examining this issue. Method. Medline, Embase, and the Cochrane central register of controlled trials were searched (through December 2012. Eligible RCTs recruited adults with erosive GERD and reported endoscopic and symptomatic relief rates at the last point of follow-up. The effect of rabeprazole versus omeprazole was reported as relative risk (RR of relief with a 95% confidence interval (CI. Results. The search identified 605 citations, and six RCTs containing 1,895 patients were eligible. Endoscopic relief rates were not significantly different between rabeprazole 20 mg and omeprazole 20 mg in treatment trials of up to 8 weeks. Heartburn relief rates were significantly different between the two groups for 8-week treatment trials. Adverse events were not significantly different between the two groups for 8-week treatment trials. Conclusion. These data suggest that rabeprazole demonstrates a clinical advantage over omeprazole in symptomatic relief but no significant difference in endoscopic relief of erosive GERD for up to 8 weeks of treatment. Rabeprazole and omeprazole were both tolerated by GERD patients.

  5. Thrombolytic treatment for acute ischemic cerebral stroke: intraarterial urokinase infusion vs. intravenous heparin and urokinase infusion

    International Nuclear Information System (INIS)

    Ko, Gi Young; Suh, Dae Chul; Lee, Jae Hong; Kim, Jun Hyoung; Choi, Choong Gon; Lee, Ho Kyu; Lee, Myoung Chong

    1996-01-01

    To evaluate the efficacy and limitation of intra-arterial urokinase (IAUK) infusion for treatment of acute cerebral stroke. Twenty-seven acute cerebral stroke patients treated with IAUK infusion within six hours of stroke onset were reviewed. All patients showed normal initial brain findings on CT. In 21 patients, urokinase(5-15 x 10 5 IU) was administered through a microcatheter placed into or proximal to occluded segment. Mechanical disruption of thrombus by guidewire was performed in 17 patients. Angiographic and clinical responses and complications after IAUK infusion, were evaluated and the results were compared with those of intravenous heparin(N=19) and urokinase infusion(N=19). Complete or partial angiographic recanalization of occluded segment was found in 18 patients (67%), and neurologic improvement was followed in 14 patients(52%). The degree of improvement on the stroke scale score after IAUK infusion was statistically more significant(p<0.05) than that shown after intravenous heparin and urokinase infusion. Complications after IAUK infusion were large(15%) and small amount intracerebral hemorrhage(15%), contrast leakage into brain parenchyma(11%), and gastrointestinal bleeding(4%). Between the IAVK and the intravenous urokinase infusion group, differences in extent and types of complications were statistically insignificant, but were significantly higher in those two groups than in the intravenous heparin infusion group. IAUK infusion may be effective for the treatment of acute cerebral stroke

  6. Effect of tumor necrosis factor-alpha infusion on the incretin effect in healthy volunteers

    DEFF Research Database (Denmark)

    Nielsen, Signe Tellerup; Lehrskov-Schmidt, Louise; Krogh-Madsen, Rikke

    2013-01-01

    Type 2 diabetes mellitus (T2DM) is associated with peripheral insulin resistance, impaired incretin effect, and increased plasma levels of tumor necrosis factor-alpha (TNF-α). Whereas TNF-α infusion at a dose that induces systemic inflammation in healthy volunteers has been demonstrated to induce...

  7. Unpredictability of regression of analgesia during the continuous postoperative extradural infusion of bupivacaine

    DEFF Research Database (Denmark)

    Mogensen, T; Hjortsø, N C; Bigler, D

    1988-01-01

    Twenty-four otherwise healthy patients scheduled for elective major abdominal surgery received general anaesthesia plus lumbar extradural analgesia. A loading dose of 0.5% plain bupivacaine was given to produce sensory analgesia (pin prick) from T4 to S5 and followed by a continuous infusion of 0...

  8. Efficacy and Safety of Pertuzumab and Trastuzumab Administered in a Single Infusion Bag, Followed by Vinorelbine

    DEFF Research Database (Denmark)

    Andersson, Michael; López-Vega, José M; Petit, Thierry

    2017-01-01

    and trastuzumab may reduce clinic time and medical resource utilization. We report results from Cohort 2, in which pertuzumab and trastuzumab were co-infused, followed by vinorelbine. PATIENTS AND METHODS: During cycle 1, patients with HER2-positive locally advanced or MBC received loading doses of pertuzumab...

  9. Localized infusion of IGF-I results in skeletal muscle hypertrophy in rats

    Science.gov (United States)

    Adams, G. R.; McCue, S. A.

    1998-01-01

    Insulin-like growth factor I (IGF-I) peptide levels have been shown to increase in overloaded skeletal muscles (G. R. Adams and F. Haddad. J. Appl. Physiol. 81: 2509-2516, 1996). In that study, the increase in IGF-I was found to precede measurable increases in muscle protein and was correlated with an increase in muscle DNA content. The present study was undertaken to test the hypothesis that direct IGF-I infusion would result in an increase in muscle DNA as well as in various measurements of muscle size. Either 0.9% saline or nonsystemic doses of IGF-I were infused directly into a non-weight-bearing muscle of rats, the tibialis anterior (TA), via a fenestrated catheter attached to a subcutaneous miniosmotic pump. Saline infusion had no effect on the mass, protein content, or DNA content of TA muscles. Local IGF-I infusion had no effect on body or heart weight. The absolute weight of the infused TA muscles was approximately 9% greater (P muscles. IGF-I infusion resulted in significant increases in the total protein and DNA content of TA muscles (P hypertrophied TA was similar to that of the contralateral muscles. These results suggest that IGF-I may be acting to directly stimulate processes such as protein synthesis and satellite cell proliferation, which result in skeletal muscle hypertrophy.

  10. Effects of leucine, isoleucine, or threonine infusion on leucine metabolism in humans

    International Nuclear Information System (INIS)

    Schwenk, W.F.; Haymond, M.W.

    1987-01-01

    Leucine and/or its α-keto acid, α-ketoisocaproate (KIC), have been reported to spare protein in humans. To determine whether specific amino acid infusions affect whole-body protein metabolism as estimated by changes in leucine flux and oxidation, five groups of normal subjects were infused with saline, leucine, isoleucine, or threonine. Independent estimates of leucine metabolism were obtained using simultaneous infusions of [ 3 H]-leucine and α-[ 14 C]ketoisocaproate. Nearly identical results were obtained using either tracer compared with the saline controls. Compared with the saline controls, leucine infusion (1) had no effect on estimated rates of appearance of endogenous leucine, (2) stimulated leucine oxidation, (3) decreased plasma concentrations of other amino acids, and (4) stimulated nonoxidized leucine disappearance in a dose-dependent fashion. In contrast, isoleucine and threonine infusions had no effect on leucine metabolism. Assuming the validity of the isotope model employed, these data suggest that the purported anabolic effect of leucine infusion on whole-body protein metabolism is mediated via stimulation of protein synthesis rather than decreased proteolysis

  11. Propofol Infusion Syndrome: A Retrospective Analysis at a Level 1 Trauma Center

    Directory of Open Access Journals (Sweden)

    James H. Diaz

    2014-01-01

    Full Text Available Objectives. The propofol infusion syndrome (PRIS, a rare, often fatal, condition of unknown etiology, is defined by development of lipemic serum, metabolic acidosis, rhabdomyolysis, hepatomegaly, cardiac arrhythmias, and acute renal failure. Methods. To identify risk factors for and biomarkers of PRIS, a retrospective chart review of all possible PRIS cases during a 1-year period was conducted at a level 1 trauma hospital in ICU patients over 18 years of age receiving continuous propofol infusions for ≥3 days. Additional study inclusion criteria included vasopressor support and monitoring of serum triglycerides and creatinine. Results. Seventy-two patients, 61 males (84.7% and 11 females (15.3%, satisfied study inclusion criteria; and of these, 3 males met the study definition for PRIS, with 1 case fatality. PRIS incidence was 4.1% with a case-fatality rate of 33%. The mean duration of propofol infusion was 6.96 days. A positive linear correlation was observed between increasing triglyceride levels and infusion duration, but no correlation was observed between increasing creatinine levels and infusion duration. Conclusions. Risk factors for PRIS were confirmed as high dose infusions over prolonged periods. Increasing triglyceride levels may serve as reliable biomarkers of impending PRIS, if confirmed in future investigations with larger sample sizes.

  12. Home therapy with continuous infusion of factor VIII after minor surgery or serious haemorrhage.

    Science.gov (United States)

    Varon, D; Schulman, S; Bashari, D; Martinowitz, U

    1996-10-01

    Administration of factor VIII (F VIII) concentrates by continuous infusion is now routinely used at several haemophilia centers but almost exclusively for hospitalized patients. We evaluated various aspects of home therapy with continuous infusion of an immunoaffinity purified F VIII concentrate (Monoclate P®, Armour) in patients who would normally have been treated with high doses in bolus injections or with continuous infusion as in-patients. Twenty haemophilia A patients, eight after minor surgery and 12 for serious haemorrhage, received continuous infusion with undiluted F VIII by a minipump for a mean of 0.9 days in the hospital, followed by 3.3 days at home. Infusion bags were exchanged every 2.5 days. No haemorrhagic complications occurred, and five haemorrhages that had been resistant to treatment with bolus injections responded promptly to the continuous infusion. There were no technical problems and patient compliance and acceptance was good. We find this mode of therapy safe, efficacious and convenient for the patients as well as for the staff.

  13. Pharmacokinetics, pharmacodynamics, and safety of esomeprazole injection/infusion in healthy Chinese volunteers: a five-way crossover study.

    Science.gov (United States)

    Yang, Hong; Li, Jingnan; Zhao, Qian; Li, Ji; Shen, Kai; Yang, Xiaoou; Jiang, Ji; Hu, Pei; Qian, Jiaming

    2013-12-01

    Esomeprazole provides effective and long lasting inhibition of gastric acid secretion. However, the pharmacokinetics and pharmacodynamics of intravenous esomeprazole in the Chinese population remain unclear. To compare the pharmacokinetics and pharmacodynamics of intravenous esomeprazole (injection and infusion) and their clinical safety and tolerability in healthy Chinese subjects. A randomized, single-center, open-label, five-way crossover study was conducted in 20 healthy volunteers. CYP2C19 metabolizer genotype and Helicobacter pylori status were examined. Five dosing regimens were used: single 40 mg injection, 40 mg infusion every 12 h, 40 mg infusion followed by continuous infusion at 8 mg/h, 80 mg infusion followed by continuous infusion at 4 or 8 mg/h. Intragastric pH was recorded within 24 h. Plasma concentration-time curve, maximum plasma concentration (Cmax ), steady state concentration, and total plasma clearance were determined. Adverse events were also recorded. Continuous infusion resulted in a higher mean area under the curve and Cmax than injection. There were no significant differences among the four infusion groups in terms of percentages of time at pH > 4, > 5, > 6, > 7 within 24 h and pH > 6 within the first 3 h. There were no significant differences in pharmacokinetic or pH values among variants of CYP2C19 genotype. The pH value within 24 h was unaffected by H. pylori infection in subjects with continuous infusion. Esomeprazole administrated by infusion produces better pharmacokinetic and intragastric pH profiles compared with those by injection. The optimal administration schedule for esomeprazole in Chinese subjects is infusion with 40 mg/12 h. © 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  14. Continuous infusion of amphotericin B: preliminary experience at Faculdade de Medicina da Fundação ABC.

    Science.gov (United States)

    Uehara, Roberto Palermo; Sá, Victor Hugo Lara de; Koshimura, Erika Tae; Prudente, Fernanda Vilas Boas; Tucunduva, Luciana Tomanik Cardozo de Mello; Gonçalves, Marina Sahade; Samano, Eliana Sueco Tibana; del Giglio, Auro

    2005-09-01

    Intravenous amphotericin B deoxycholate (AmB-D) infusions, usually given over 4 hours, frequently induce nephrotoxicity and undesirable infusion-related side effects such as rigors and chills. There is evidence in the literature that the use of AmB-D in the form of continuous 24-hour infusion is less toxic than the usual four-hour infusion of this drug. Our objective was to evaluate the efficacy and safety of continuous infusion of AmB-D for the treatment of persistent fever in neutropenic patients with hematological malignancies after chemotherapy. Observational retrospective analysis of our experience with continuous infusion of AmB-D, at Faculdade de Medicina da Fundação ABC and Hospital Estadual Mário Covas in Santo André. From October 2003 to May 2004, 12 patients with hematological malignancies and chemotherapy-induced neutropenia received 13 cycles of continuous infusion of AmB-D. The median dose of AmB-D was 0.84 mg/kg/day (0.33 to 2.30 mg/kg/day). Concomitant use of nephrotoxic medications occurred in 92% of the cycles. Nephrotoxicity occurred in 30.76% of the cycles, hypokalemia in 16.67%, hepatotoxicity in 30% and adverse infusion-related events in 23%. All patients survived for at least seven days after starting continuous infusion of AmB-D, and clinical resolution occurred in 76% of the cycles. Continuous infusion of AmB-D can be used in our Institution as an alternative to the more toxic four-hour infusion of AmB-D and possibly also as an alternative to the more expensive liposomal formulations of the drug.

  15. Cotreatment with dichloroacetate and omeprazole exhibits a synergistic antiproliferative effect on malignant tumors

    Science.gov (United States)

    ISHIGURO, TATSUAKI; ISHIGURO, MIYU; ISHIGURO, RYUMEI; IWAI, SAYURI

    2012-01-01

    It has been reported that treating cancer cells with dichloroacetate (DCA), an approved treatment for congenital lactic acidosis, reverses the Warburg effect and inhibits tumor growth). Furthermore, omeprazole (OMP) is a well-known agent that enhances the effects of anticancer drugs. The aim of this study was to find clinically-used drugs that enhance the effects of DCA. The combination of DCA and OMP exhibited a more potent antitumor activity than DCA alone in HT1080 fibrosarcoma cells and RKO colon cancer cells, while the drugs did not affect the proliferation of WI-38 human fibroblasts. The inhibitory effect of DCA combined with OMP was reversed with vitamin E and Z-VAD-FMK; therefore conventional caspase-dependent cell growth inhibition through superoxide production was suggested as the mechanism for inhibition. The combination of these drugs also had an effect on HT1080 fibrosarcoma cells inoculated into mice. Since OMP and DCA may be administered orally and have been used clinically for several years without major side effects, we believe that this combination therapy could be readily translated to treat malignant tumors. PMID:22740984

  16. Histamine stimulates chloride secretion in omeprazole-inhibited frog gastric mucosa

    International Nuclear Information System (INIS)

    McGreevy, J.; Barton, R.; Housinger, T.

    1986-01-01

    Omeprazole (OME) stops hydrogen ion (H) secretion in the histamine (HIST)-stimulated gastric mucosa while the chloride (Cl) which had accompanied the H continues to be pumped into the lumen. This finding suggests that the Cl pump is independent of the H/K ATP-ase driven H pump. To test this hypothesis, 16 Ussing-chambered frog mucosas were exposed to OME prior to HIST stimulation. If the Cl pump is independent, HIST should stimulate Cl secretion in the OME-inhibited mucosa. A 1 hr control (CON) interval preceded exposure to OME (10 -4 M) in the nutrient solution. Potential difference (PD), short-circuit current (Isc), resistance (R), H flux (J/sup H/) and Cl flux (J/sup Cl/ with 36 Cl) were measured every 15 min. After 1 hr of OME exposure, HIST (10 -5 M) was added to the nutrient solution. The findings demonstrate that HIST stimulates Cl secretion in the OME-inhibited bullfrog gastric mucosa

  17. The Protective Effect of Omeprazole Against Traumatic Brain Injury: An Experimental Study.

    Science.gov (United States)

    Özay, Rafet; Türkoğlu, Mehmet Erhan; Gürer, Bora; Dolgun, Habibullah; Evirgen, Oya; Ergüder, Berrin İmge; Hayırlı, Nazlı; Gürses, Levent; Şekerci, Zeki

    2017-08-01

    The development of secondary brain injury via oxidative stress after traumatic brain injury (TBI) is a well-known entity. Consequently, the aim of the present study was to evaluate the role of omeprazole (OM) on rat model of TBI. A total of 24 male rats were used and divided into 4 groups as follows; control, trauma, OM, and methylprednisolone (MP). The trauma, OM, and MP groups were subjected to closed-head contusive weight-drop injuries. Rats received treatment with saline, OM, or MP, respectively. All the animals were sacrificed at 24 hours after trauma and brain tissues were extracted. The oxidant/antioxidant parameters (malondialdehyde, glutathione peroxidase, superoxide dismutase, nitric oxide) and caspase-3 in the cerebral tissue were analyzed, and histomorphologic evaluation of the cerebral tissue was performed. Levels of MDA and activity of caspase-3 were significantly reduced in the OM and MP groups compared with the trauma group. Glutathione peroxidase and superoxide dismutase levels were increased both in the OM and MP groups compared with the trauma group. The pathology scores were statistically lower in the OM and MP groups than the trauma group. The results of the present study showed that OM was as effective as MP in protecting brain from oxidative stress, and apoptosis in the early phase of TBI. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Honeycomb structural composite polymer network of gelatin and functional cellulose ester for controlled release of omeprazole.

    Science.gov (United States)

    Zhuang, Chen; Shi, Chengmei; Tao, Furong; Cui, Yuezhi

    2017-12-01

    The functionalized cellulose ester MCN was firstly synthesized and used to cross-link gelatin by amidation between -NH 2 in gelatin and active ester groups in MCN to form a composite polymer network Gel-MCN, which was confirmed by Van Slyke method, FTIR, XRD and TGA-DTG spectra. The model drug omeprazole was loaded in Gel-MCN composites mainly by electrostatic interaction and hydrogen bonds, which were certified by FTIR, XRD and TGA-DSC. Thermal stability, anti-biodegradability, mechanical property and surface hydrophobicity of the composites with different cross-linking extents and drug loading were systematically investigated. SEM images demonstrated the honeycomb structural cells of cross-linked gelatin networks and this ensured drug entrapment. The drug release mechanism was dominated by a combined effect of diffusion and degradation, and the release rate decreased with cross-linking degree increased. The developed drug delivery system had profound significance in improving pesticide effect and bioavailability of drugs. Copyright © 2017. Published by Elsevier B.V.

  19. Histamine stimulates chloride secretion in omeprazole-inhibited frog gastric mucosa

    Energy Technology Data Exchange (ETDEWEB)

    McGreevy, J.; Barton, R.; Housinger, T.

    1986-03-05

    Omeprazole (OME) stops hydrogen ion (H) secretion in the histamine (HIST)-stimulated gastric mucosa while the chloride (Cl) which had accompanied the H continues to be pumped into the lumen. This finding suggests that the Cl pump is independent of the H/K ATP-ase driven H pump. To test this hypothesis, 16 Ussing-chambered frog mucosas were exposed to OME prior to HIST stimulation. If the Cl pump is independent, HIST should stimulate Cl secretion in the OME-inhibited mucosa. A 1 hr control (CON) interval preceded exposure to OME (10/sup -4/M) in the nutrient solution. Potential difference (PD), short-circuit current (Isc), resistance (R), H flux (J/sup H/) and Cl flux (J/sup Cl/ with /sup 36/Cl) were measured every 15 min. After 1 hr of OME exposure, HIST (10/sup -5/M) was added to the nutrient solution. The findings demonstrate that HIST stimulates Cl secretion in the OME-inhibited bullfrog gastric mucosa.

  20. Efeito do omeprazol e do pantoprazol sobre a regeneração hepática após hepatectomia parcial em ratos Effect of omeprazole and pantoprazole on liver regeneration after partial hepatectomy in rats

    Directory of Open Access Journals (Sweden)

    Gustavo Barreto de Melo

    2003-12-01

    Full Text Available OBJETIVO: Avaliar os efeitos do omeprazol e do pantoprazol sobre a regeneração hepática após hepatectomia parcial. MÉTODOS: Cinqüenta e oito ratos Wistar machos foram divididos em 4 grupos: Grupo SHAM, Grupo HP, Grupo PANTO e Grupo OMEP. Eles foram submetidos a hepatectomia parcial de 67% (Grupos HP, PANTO e OMEP ou laparotomia (Grupo SHAM. Os fígados foram removidos 32 e 56 horas após a operação. Depois, os animais foram sacrificados. Em todos os grupos, as substâncias (solução salina, omeprazol e pantoprazol foram aplicadas diariamente a partir do momento em que foram operados até o sacrifício. RESULTADOS: O índice de mitose no Grupo SHAM não foi significativo. Trinta e duas horas após a hepatectomia, a contagem de mitoses foi de 1,2 ± 1,09 para o Grupo HP, 1,2 ± 1,6 para o Grupo OMEP e 2,6 ± 3,2 para o Grupo PANTO. Na análise após 56 horas, os valores foram 1,6 ± 0,89 para o HP, 2 ± 1,8 para o OMEP e 2,6 ± 0,54 para o PANTO. Esses resultados não foram estatisticamente significativos. CONCLUSÃO: O omeprazol e o pantoprazol, agentes inibidores da bomba de prótons (H+, K+-ATPase, não interferem na regeneração hepática 32 e 56 horas após hepatectomia parcial a 67% em ratos.PURPOSE: To assess the effects of omeprazole and pantoprazole on liver regeneration after partial hepatectomy. METHODS: Fifty eight male Wistar rats were divided into 4 groups: SHAM, HP, PANTO and OMEP Groups. They were submitted to 67% partial hepatectomy (HP, PANTO and OMEP Groups or laparotomy (SHAM Group. Their livers were removed 32 and 56 hours after the operation. Then, the animals were sacrificed. In all groups, the substances (saline solution, omeprazole and pantoprazole were injected once daily from the moment they were operated on until the time of sacrifice. RESULTS: In SHAM Group the mitotic index was not significant. Thirty two hours after hepatectomy, the mitosis index was 1.2 ± 1.09 in HP Group, 1.2 ± 1.6 in OMEP Group and 2

  1. Carbon Nanotube Infused Launch Vehicle Structures

    Data.gov (United States)

    National Aeronautics and Space Administration — For the past 5 years Orbital ATK has been investing in, prototyping, and testing carbon nanotube infused composite structures to evaluate their impact on launch...

  2. New single capsule of bismuth, metronidazole and tetracycline given with omeprazole versus quadruple therapy consisting of bismuth, omeprazole, amoxicillin and clarithromycin for eradication of Helicobacter pylori in duodenal ulcer patients: a Chinese prospective, randomized, multicentre trial.

    Science.gov (United States)

    Xie, Yong; Pan, Xiaolin; Li, Yan; Wang, Huahong; Du, Yiqi; Xu, Jianming; Wang, Jiangbin; Zeng, Zhirong; Chen, Ye; Zhang, Guoxin; Wu, Kaichun; Liu, Dongsheng; Lv, Nonghua

    2018-03-27

    To assess the efficacy and safety of omeprazole given with the new single capsule of bismuth, metronidazole and tetracycline (OBMT) compared with quadruple treatment consisting of omeprazole, bismuth, amoxicillin and clarithromycin (OBAC) for Helicobacter pylori eradication in duodenal ulcer patients. This single-blind, randomized multicentre trial was conducted in 10 tertiary hospitals in China between January 2013 and April 2014. Patients were randomized to receive 10 days of OBMT therapy or 10 days of OBAC therapy. Our primary outcome was the H. pylori eradication rate, confirmed by negative [13C]urea breath tests 20-25 days after the end of omeprazole maintenance. Antibiotic resistance was determined by Etest. This study is registered with ClinicalTrials.gov, number ChiCTR-TRC-13003143. One hundred and ninety-two patients received OBMT therapy and 192 received OBAC therapy. There was no significant difference between the eradication rates achieved by OBMT and OBAC in either the ITT analysis (86.46% versus 87.50%, P = 0.762) or the PP analysis (94.58% versus 93.06%, P = 0.563). The efficacies of OBMT and OBAC were not affected by metronidazole or clarithromycin resistance. Treatment-emergent adverse events (TEAEs) for both treatments were similar; gastrointestinal and CNS symptoms were the most commonly reported. The new single-capsule OBMT quadruple therapy is as effective and well tolerated as the widely used OBAC therapy for treatment of H. pylori in clinical practice in China. In addition, this OBMT therapy largely overcomes H. pylori metronidazole and clarithromycin resistance.

  3. Infusion Antihypoxants in Children with Critical Conditions

    Directory of Open Access Journals (Sweden)

    Yu. S. Aleksandrovich

    2014-01-01

    Full Text Available Hypoxia and mitochondrial damage are a key component of the pathogenesis and tanatogenesis of a critical condition, suggesting the need for its prevention and maximally rapid elimination. Objective: to analyze the efficacy and safety of infusion antihypoxants used in critically ill children from the results of researches. Materials and methods. Available investigations dealing with infusion therapy in children and papers on the use of infusion antihypoxants in adults in 2005 to 2013 were sought in the medical databases PubMed and Cochrane Library with their free availability and analyzed. Results. The analysis included 70 trials. The pathophysiology and pathobiochemistry of hypoxia in critically ill children are given; the current principles of its correction by infusion therapy are considered in detail. Particular emphasis is placed on trials evaluating the efficacy and safety of succinic acid solutions in children. Main indications for and contraindications to their use are demonstrated. Conclusion. The use of Krebs cycle substrate-based infusion antihypoxants (malate, succinate is an effective and promising procedure for the intensive therapy and correction of hypoxia in both adults and children with critical conditions. Considering the fact that papers on the use of infusion antihypoxants in children are scanty, there is a need for further investigations. 

  4. A Prospective, Placebo-Controlled Pilot Evaluation of the Effect of Omeprazole on Serum Calcium, Magnesium, Cobalamin, Gastrin Concentrations, and Bone in Cats.

    Science.gov (United States)

    Gould, E; Clements, C; Reed, A; Giori, L; Steiner, J M; Lidbury, J A; Suchodolski, J S; Brand, M; Moyers, T; Emery, L; Tolbert, M K

    2016-05-01

    Chronic proton pump inhibitor administration has been associated with electrolyte and cobalamin deficiency, disrupted bone homeostasis, hypergastrinemia, and rebound acid hypersecretion in humans. It is unknown if this occurs in cats. Prolonged oral omeprazole results in altered bone mineral density or content, serum calcium, magnesium, cobalamin, and gastrin concentrations in healthy cats. Six healthy adult DSH cats. In a within subjects, before and after design, cats received placebo followed by omeprazole (0.83-1.6 mg/kg PO q12h) for 60 days each. Analysis of serum calcium, magnesium, cobalamin, and gastrin concentrations was performed on days 0, 30, and 60. Bone density and content were evaluated on days 0 and 60 of each intervention. Continuous data were analyzed using a two-way ANOVA (α = 0.006). On day 60 of omeprazole administration, continuous intragastric pH monitoring was performed in 2 cats to evaluate the effects of abrupt withdrawal of omeprazole. No significant changes were detected between treatments for any variables, except serum gastrin, which was significantly higher during omeprazole treatment in comparison to placebo (P = 0.002). Evidence of gastric hyperacidity was seen in both cats in which intragastric pH monitoring was performed following cessation of omeprazole. Although further studies with larger populations of cats will be needed to draw any definitive conclusions, these preliminary results suggest that prolonged PPI treatment results in hypergastrinemia and abrupt PPI withdrawal might result in RAH in cats. Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  5. Omeprazole induces heme oxygenase-1 in fetal human pulmonary microvascular endothelial cells via hydrogen peroxide-independent Nrf2 signaling pathway.

    Science.gov (United States)

    Patel, Ananddeep; Zhang, Shaojie; Shrestha, Amrit Kumar; Maturu, Paramahamsa; Moorthy, Bhagavatula; Shivanna, Binoy

    2016-11-15

    Omeprazole (OM) is an aryl hydrocarbon receptor (AhR) agonist and a proton pump inhibitor that is used to treat humans with gastric acid related disorders. Recently, we showed that OM induces NAD (P) H quinone oxidoreductase-1 (NQO1) via nuclear factor erythroid 2-related factor 2 (Nrf2)-dependent mechanism. Heme oxygenase-1 (HO-1) is another cytoprotective and antioxidant enzyme that is regulated by Nrf2. Whether OM induces HO-1 in fetal human pulmonary microvascular endothelial cells (HPMEC) is unknown. Therefore, we tested the hypothesis that OM will induce HO-1 expression via Nrf2 in HPMEC. OM induced HO-1 mRNA and protein expression in a dose-dependent manner. siRNA-mediated knockdown of AhR failed to abrogate, whereas knockdown of Nrf2 abrogated HO-1 induction by OM. To identify the underlying molecular mechanisms, we determined the effects of OM on cellular hydrogen peroxide (H 2 O 2 ) levels since oxidative stress mediated by the latter is known to activate Nrf2. Interestingly, the concentration at which OM induced HO-1 also increased H 2 O 2 levels. Furthermore, H 2 O 2 independently augmented HO-1 expression. Although N-acetyl cysteine (NAC) significantly decreased H 2 O 2 levels in OM-treated cells, we observed that OM further increased HO-1 mRNA and protein expression in NAC-pretreated compared to vehicle-pretreated cells, suggesting that OM induces HO-1 via H 2 O 2 -independent mechanisms. In conclusion, we provide evidence that OM transcriptionally induces HO-1 via AhR - and H 2 O 2 - independent, but Nrf2 - dependent mechanisms. These results have important implications for human disorders where Nrf2 and HO-1 play a beneficial role. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Modeling the cost-effectiveness of ilaprazole versus omeprazole for the treatment of newly diagnosed duodenal ulcer patients in China.

    Science.gov (United States)

    Xuan, J W; Song, R L; Xu, G X; Lu, W Q; Lu, Y J; Liu, Z

    2016-11-01

    To evaluate the cost-effectiveness of 10 mg ilaprazole once-daily vs 20 mg omeprazole once-daily to treat newly-diagnosed duodenal ulcer patients in China. A decision tree model was constructed and the treatment impact was projected up to 1 year. The CYP2C19 polymorphism distribution in the Chinese population, the respective cure rates in the CYP2C19 genotype sub-groups, the impact of Duodenal Ulcer (DU) on utility value and drug-related side-effect data were obtained from the literature. The total costs of medications were calculated to estimate the treatment costs based on current drug retail prices in China. Expert surveys were conducted when published data were not available. Probabilistic sensitivity analysis was performed to gauge the robustness of the results. Ilaprazole, when compared with omeprazole, achieved a better overall clinical efficacy. For the overall population, ilaprazole achieved an incremental cost effectiveness ratio (ICER) of ¥132 056 per QALY gained. This is less than the WHO recommended threshold of 3-times the average GDP per capita in China (2014). Furthermore, sub-group analysis showed that ilaprazole is cost-effective in every province in CYP2C19 hetEM patients and in the most developed provinces in CYP2C19 homEM patients. Probabilistic sensitivity analysis suggests that the results are robust with 97% probability that ilaprozole is considered cost-effective when a threshold of 3-times China's average GDP per capita is considered. This study didn't have the data of ilaprazole combined with Hp eradication therapy. Caution should be taken when extrapolating these findings to DU patients with an Hp eradication therapy. The cost-effectiveness analysis results demonstrated that ilaprazole would be considered a cost-effective therapy, compared with omeprazole, in Chinese DU patients based on the efficacy projections in various CYP2C19 polymorphism types.

  7. A Case-Control Study of Esomeprazole plus Rebamipide vs. Omeprazole plus Rebamipide on Post-ESD Gastric Ulcers

    Directory of Open Access Journals (Sweden)

    Maki Bunno

    2013-01-01

    Full Text Available Objectives Endoscopic submucosal dissection (ESD is useful for treating gastric tumors. Several trials have shown the efficacy of 4 or 8 weeks of proton pump inhibitor (PPI administration for post-ESD ulcers. However, if the size of the post-ESD ulcer is larger than predicted, PPI administration alone might not be sufficient for the ulcer to heal within 4 weeks. There is no report about the efficacy of post-ESD gastric ulcers by esomeprazole. We examined retrospectively the efficacy of a combination therapy of esomeprazole plus rebamipide, a mucosal-protective antiulcer drug, on the acceleration of post-ESD ulcer healing comparing with omeprazole plus rebamipide. Methods We reviewed the medical records of patients who underwent ESD for gastric neoplasia. We conducted a case-control study to compare the healing rates within 4 weeks effected by esomeprazole plus rebamipide (group E and omeprazole plus rebamipide (group O. The sizes of the artificial ulcers were divided into normal-sized or large-sized. Results The baseline characteristics did not differ significantly between the two groups except age and sex. Stage S1 disease was observed in 27.6% and 38.7% of patients after 4 weeks of treatment in the group E and O, respectively. In large-sized artificial ulcers, the healing rate of stage S1 in group E is significantly higher than that in group O in 4 weeks.(25% VS 0%: P = 0.02 Conclusions The safety and efficacy profiles of esomeprazole plus rebamipide and omeprazole and rebamipide are similar for the treatment of ESD-induced ulcers. In large-sized ulcers, esomeprazole plus rebamipide promotes ulcer healing.

  8. Therapeutic usage of omeprazole and corticoid in a dog with hydrocephalus unresponsive to conventional therapyUso terapêutico da associação do omeprazol com corticóide em um cão com hidrocefalia não-responsiva ao tratamento convencional

    Directory of Open Access Journals (Sweden)

    Alexandre Mendes Amude

    2013-05-01

    Full Text Available Medical therapy for hydrocephalus includes the administration of medications to limit the production of the cerebrospinal fluid (CSF resulting in reduced intracranial pressure (ICP. This report describes the clinical findings in one dog with congenital hydrocephalus that was unresponsive to conventional medical treatment with steroids, but demonstrated good response to omeprazole when this drug was added to the steroid. Omeprazole might decrease the CSF production by about 26% according to experimental studies with healthy dogs, but the usage of the omeprazole in clinical trials with affected dogs such as hydrocephalic animals is lacking. The results of this report might suggest that omeprazole can be used added to steroids to ameliorate the neurological status in dogs with increased ICP by hydrocephalus.O tratamento médico para a hidrocefalia inclui a administração de medicamentos para limitar a produção do fluido cerebroespinhal (FCE, resultando em redução da pressão intracraniana (PIC. Este trabalho descreve os achados clínicos em um cão com hidrocefalia congênita não responsiva ao tratamento médico convencional com esteróides mas que apresentou boa resposta à associação omeprazolesteróides. O omeprazol pode diminuir a produção de FCE em cerca de 26% de acordo com estudos experimentais realizados com cães saudáveis. Porém, o uso do omeprazol em ensaios clínicos com cães enfermos, como os animais hidrocefálicos, não é descrito. Os resultados deste trabalho sugerem que o omeprazol pode ser empregado em associação ao corticóide para melhorar o estado neurológico em cães com aumento da PIC devido à hidrocefalia.

  9. Dexmedetomidine Infusion Associated with Transient Adrenal Insufficiency in a Pediatric Patient: A Case Report

    Directory of Open Access Journals (Sweden)

    Elizabeth W. Tucker

    2013-01-01

    Full Text Available Dexmedetomidine is a highly selective α2-adrenoceptor agonist used for sedation due to its anxiolytic and analgesic properties without respiratory compromise. Due to its structural similarity to etomidate, there has been concern that dexmedetomidine may cause adrenal insufficiency. This concern was initially supported by animal studies, but subsequent human studies demonstrated mixed results. We describe the case of transient adrenal insufficiency in a 1-year-old male who presented with 24% total body surface 2nd degree burns. He required sedation with a prolonged, high-dose dexmedetomidine infusion with a peak infusion dose of 2.7 mcg/kg/hr and duration of 6.5 days. The patient developed lethargy and hypotension four days after discontinuation of his infusion. He had a random cortisol level which was low at 0.4 mcg/dL, and the concern for adrenal suppression was confirmed with an ACTH stimulation test with the baseline cortisol of 0.4 mcg/dL and inappropriate 60 minute post-ACTH stimulation cortisol of 7.8 mcg/dL. While further studies will be needed to clarify the risk of adrenal suppression secondary to dexmedetomidine, this case suggests that caution should be taken when administering dexmedetomidine to pediatric patients and highlights the need for future studies to look at appropriate dosing and duration of dexmedetomidine infusions.

  10. Decreasing the infusion rate reduces the proarrhythmic risk of NS-7

    DEFF Research Database (Denmark)

    Detre, Elke; Thomsen, Morten Bækgaard; Beekman, Jet D

    2005-01-01

    1 The rate of infusion has been suggested to be important for drug-induced torsades de pointes (TdP) arrhythmias. We investigated the repolarisation-prolonging effects and proarrhythmic properties of NS-7, a neuroprotective drug in development, using two different infusion rates. 2 A fast (5 min...... intravenously (i.v.)) escalating dosing regimen (0.3 and 3.0 mg kg(-1), n=4) of NS-7 was investigated in anaesthetised control dogs in sinus rhythm (SR). This was compared to a slow infusion (60 min i.v.) of one dose (3.0 mg kg(-1), n=4) NS-7. The similar dosing regimens were investigated in anaesthetised dogs...... with chronic, complete AV block (CAVB), an animal model of TdP (n=6). 3 No electrophysiological effects were seen after 0.3 mg kg(-1) NS-7. Fast infusion of 3.0 mg kg(-1) caused prolongation of repolarisation, for example, heart rate corrected QT interval (QT(c)): in SR: 6+/-1%; in CAVB: 10+/-7%, which...

  11. Complications Following Balloon-Occluded Arterial Infusion Chemotherapy for Pelvic Malignancies

    International Nuclear Information System (INIS)

    Sugimoto, Koji; Hirota, Shozo; Imanaka, Kazufumi; Kawabe, Tetsuya; Nakayama, Yoshiharu; Takeuchi, Yasuhito

    1999-01-01

    Purpose: To evaluate the incidence and causes of complications associated with balloon-occluded arterial infusion chemotherapy (BOAI) for pelvic malignancies. Methods: In 34 courses of BOAI in 22 patients with pelvic malignancies, we analyzed the incidence of complications as well as the effect of the dose of the anticancer drugs, the infusion site, and the number of BOAI administrations on these complications. Complications were divided into two categories: cystitis-like symptoms and neurological complications such as pain, numbness, and paresthesia of the lower extremities and the hip. Results: Eleven patients (50%) suffered from complications, seven (31.8%) from neurological complications and four (18.2%) from cystitis-like symptoms. The complications appeared in 14 courses (42.4%) of BOAI, neurological complications in 10 (30.3%) and cystitis-like symptoms in four (12.1%). A high dose of anti-cancer drugs and infusion from the anterior division tended to induce neurological complications more frequently; however, the cystitis-like symptoms were not related to any factors. Conclusion: Our results indicate that a smaller dose of anti-cancer drugs should be infused from the bilateral internal iliac arteries for safer pelvic BOAI

  12. A remote drip infusion monitoring system employing Bluetooth.

    Science.gov (United States)

    Amano, Hikaru; Ogawa, Hidekuni; Maki, Hiromichi; Tsukamoto, Sosuke; Yonezawa, Yoshiharu; Caldwell, W Morton

    2012-01-01

    We have developed a remote drip infusion monitoring system for use in hospitals. The system consists of several infusion monitoring devices and a central monitor. The infusion monitoring device employing a Bluetooth module can detect the drip infusion rate and an empty infusion solution bag, and then these data are sent to the central monitor placed at the nurses' station via the Bluetooth. The central monitor receives the data from several infusion monitoring devices and then displays graphically them. Therefore, the developed system can monitor intensively the drip infusion situation of the several patients at the nurses' station.

  13. Subcutaneous insulin infusion: change in basal infusion rate has no immediate effect on insulin absorption rate

    International Nuclear Information System (INIS)

    Hildebrandt, P.; Birch, K.; Jensen, B.M.; Kuehl, C.

    1986-01-01

    Eight insulin-dependent diabetic patients were simultaneously given subcutaneous infusions (1.12 IU/h each) of 125 I-labeled Actrapid insulin in each side of the abdominal wall. After 24 h of infusion, the size of the infused insulin depots was measured by external counting for 5 h. The basal infusion rate was then doubled in one side and halved in the other for the next 4 h. Finally, 1.12 IU/h of insulin was given in both sides of the abdominal wall for an additional 3 h. The changes in the size of the depots were measured, and the absorption rates for each hour were calculated. During the first 5 h of infusion, the depot size was almost constant (approximately 5 IU) with an absorption rate that equaled the infusion rate. Doubling the infusion rate led to a significant increase in depot size, but the absorption rate remained unchanged for the first 3 h, and only thereafter was a significant increase seen. When the infusion rate was reduced to the initial 1.12 IU/h, the absorption rate remained elevated during the next 3 h. Correspondingly, when the infusion rate was decreased, the depot size also decreased, but the absorption rate remained unchanged for the first 3 h. The results show that a change in the basal insulin infusion rate does not lead to any immediate change in the insulin absorption rate. This should be considered when planning an insulin-infusion program that includes alteration(s) in the basal-rate setting

  14. Effects of omeprazole or pantoprazole on platelet function in non-ST-segment elevation acute coronary syndrome patients receiving clopidogrel.

    Science.gov (United States)

    Gu, Ruo-Xi; Wang, Xiao-Zeng; Li, Jing; Deng, Jie; Li, Xing-Xing; Wang, Jiao

    2016-01-01

    This study evaluated the effect of omeprazole or pantoprazole on platelet reactivity in non-ST-segment elevation acute coronary syndrome (NSTE-ACS) patients receiving clopidogrel. Consecutive patients with NSTE-ACS ( n  = 620) from general hospital of Shenyang Military Command were randomized to the omeprazole or pantoprazole (20 mg/d) group (1:1), and received routine dual antiplatelet treatment. Patients' reversion rate of adenosine diphosphate-induced platelet aggregation (ADP-PA) was assessed at baseline, 12 to 24 h after administration of medication, and after 72 h of percutaneous coronary intervention (PCI). The primary endpoint of the study was platelet reactivity assessed with ADP-PA at 30 days after PCI. Adverse events (AEs) were recorded for 30-day and 180-day follow-up periods. There were no significant differences between both the groups in platelet response to clopidogrel at 12-24 h after drug administration (54.09% ± 18.90% vs 51.62% ± 19.85%, P  = 0.12), 72 h after PCI (52.15% ± 19.45% vs 49.66% ± 20.05%, P  = 0.18), and 30 days after PCI (50.44% ± 14.54% vs 48.52% ± 15.08%, P  = 0.17). The rate of AEs did not differ significantly between groups during the 30-day (15.2% vs 14.8%, P  = 0.91) and 180-day (16.5% vs 14.5%, P  = 0.50) follow-up periods after PCI. The addition of omeprazole or pantoprazole to clopidogrel did not restrict the effect of platelet aggregation by reducing the conversion of clopidogrel. Compared with clopidogrel alone, pantoprazole-clopidogrel and omeprazole-clopidogrel combinations did not increase the incidence of adverse clinical events during 30-day and 180-day follow-up periods after PCI. The study is registered in the National Institutes of Health website with identifier NCT01735227. Registered 14 November 2012.

  15. Effectiveness of high dose remifentanil in preventing coughing and laryngospasm in non-paralyzed patients for advanced bronchoscopic procedures

    Directory of Open Access Journals (Sweden)

    Basavana Gouda Goudra

    2014-01-01

    Conclusions: High dose of remifentanil infusion is associated with a lower incidence of coughing and laryngospasms during bronchoscopy. Simultaneously, it improves Pulmonologist′s satisfaction and procedural conditions.

  16. Síndrome da infusão do propofol Síndrome de la infusión del propofol Propofol infusion syndrome

    Directory of Open Access Journals (Sweden)

    Fabiano Timbó Barbosa

    2007-10-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: A síndrome da infusão do propofol tem sido descrita como uma síndrome rara e quase sempre fatal que ocorre após infusão prolongada desse fármaco. Ela pode resultar em acidose metabólica grave, rabdomiólise, colapso cardiovascular e morte. O objetivo deste artigo foi mostrar aspectos relacionados com a síndrome da infusão do propofol por meio da revisão de literatura. CONTEÚDO: Estão definidas as características da síndrome da infusão do propofol quanto à fisiopatologia, características clínicas, tratamento e recomendações de dose para pacientes gravemente enfermos. CONCLUSÕES: O propofol deve ser usado com cautela quando se planeja seu uso sob regime de infusão contínua por períodos prolongados. O surgimento de sinais sugestivos da síndrome da infusão do propofol indica a suspensão imediata do fármaco e início de medidas de suporte.JUSIFICATIVA Y OBJETIVOS: El síndrome de la infusión del propofol ha sido descrito como un síndrome raro y frecuentemente fatal que ocurre después de la infusión prolongada de ese fármaco. Puede resultar en acidez metabólica grave, rabdomiólisis, colapso cardiovascular y deceso. El objetivo de este artículo fue mostrar aspectos relacionados al síndrome de la infusión del propofol a través de la revisión de la literatura. CONTENIDO: Están definidas las características del síndrome de la infusión del propofol en cuanto a la fisiopatología, características clínicas, tratamiento y recomendaciones de dosis para pacientes gravemente enfermos. CONCLUSIONES: El propofol debe ser usado con cautela cuando se planea su uso bajo el régimen de infusión continua por períodos prolongados. El aparecimiento de señales sugestivas del síndrome de la infusión del propofol indica la suspensión inmediata del fármaco y el inicio de medidas de soporte.BACKGROUND AND OBJECTIVES: Propofol infusion syndrome has been described as a rare, and frequently fatal

  17. A Solid-Contact Indium(III) Sensor based on a Thiosulfinate Ionophore Derived from Omeprazole

    Energy Technology Data Exchange (ETDEWEB)

    Abbas, Mohammad Nooredeen; Hend Samy Amer [National Research Centre, Cairo (Egypt)

    2013-04-15

    A novel solid-contact indium(III)-selective sensor based on bis-(1H-benzimidazole-5-methoxy-2-[(4-methoxy-3, 5-dimethyl-1-pyridinyl) 2-methyl]) thiosulfinate, known as an omeprazole dimer (OD) and a neutral ionophore, was constructed, and its performance characteristics were evaluated. The sensor was prepared by applying a membrane cocktail containing the ionophore to a graphite rod pre-coated with polyethylene dioxythiophene (PEDOT) conducting polymer as the ion-to-electron transducer. The membrane contained 3.6% OD, 2.3% oleic acid (OA) and 62% dioctyl phthalate (DOP) as the solvent mediator in PVC and produced a good potentiometric response to indium(III) ions with a Nernstian slope of 19.09 mV/decade. The constructed sensor possessed a linear concentration range from 3 Χ 10{sup -7} to 1 Χ 10{sup -2} M and a lower detection limit (LDL) of 1 Χ 10{sup -7} M indium(III) over a pH range of 4.0-7.0. It also displayed a fast response time and good selectivity for indium(III) over several other ions. The sensor can be used for longer than three months without any considerable divergence in potential. The sensor was utilized for direct and flow injection potentiometric (FIP) determination of indium(III) in alloys. The parameters that control the flow injection method were optimized. Indium(III) was quantitatively recovered, and the results agreed with those obtained using atomic absorption spectrophotometry, as confirmed by the f and t values. The sensor was also utilized as an indicator electrode for the potentiometric titration of fluoride in the presence of chloride, bromide, iodide and thiocyanate ions using indium(III) nitrate as the titrant.

  18. A Solid-Contact Indium(III) Sensor based on a Thiosulfinate Ionophore Derived from Omeprazole

    International Nuclear Information System (INIS)

    Abbas, Mohammad Nooredeen; Hend Samy Amer

    2013-01-01

    A novel solid-contact indium(III)-selective sensor based on bis-(1H-benzimidazole-5-methoxy-2-[(4-methoxy-3, 5-dimethyl-1-pyridinyl) 2-methyl]) thiosulfinate, known as an omeprazole dimer (OD) and a neutral ionophore, was constructed, and its performance characteristics were evaluated. The sensor was prepared by applying a membrane cocktail containing the ionophore to a graphite rod pre-coated with polyethylene dioxythiophene (PEDOT) conducting polymer as the ion-to-electron transducer. The membrane contained 3.6% OD, 2.3% oleic acid (OA) and 62% dioctyl phthalate (DOP) as the solvent mediator in PVC and produced a good potentiometric response to indium(III) ions with a Nernstian slope of 19.09 mV/decade. The constructed sensor possessed a linear concentration range from 3 Χ 10 -7 to 1 Χ 10 -2 M and a lower detection limit (LDL) of 1 Χ 10 -7 M indium(III) over a pH range of 4.0-7.0. It also displayed a fast response time and good selectivity for indium(III) over several other ions. The sensor can be used for longer than three months without any considerable divergence in potential. The sensor was utilized for direct and flow injection potentiometric (FIP) determination of indium(III) in alloys. The parameters that control the flow injection method were optimized. Indium(III) was quantitatively recovered, and the results agreed with those obtained using atomic absorption spectrophotometry, as confirmed by the f and t values. The sensor was also utilized as an indicator electrode for the potentiometric titration of fluoride in the presence of chloride, bromide, iodide and thiocyanate ions using indium(III) nitrate as the titrant

  19. New Sensitive Kinetic Spectrophotometric Methods for Determination of Omeprazole in Dosage Forms

    Directory of Open Access Journals (Sweden)

    Ashraf M. Mahmoud

    2009-01-01

    Full Text Available New rapid, sensitive, and accurate kinetic spectrophotometric methods were developed, for the first time, to determine omeprazole (OMZ in its dosage forms. The methods were based on the formation of charge-transfer complexes with both iodine and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ. The variables that affected the reactions were carefully studied and optimized. The formed complexes and the site of interaction were examined by UV/VIS, IR, and 1H-NMR techniques, and computational molecular modeling. Under optimum conditions, the stoichiometry of the reactions between OMZ and the acceptors was found to be 1 : 1. The order of the reactions and the specific rate constants were determined. The thermodynamics of the complexes were computed and the mechanism of the reactions was postulated. The initial rate and fixed time methods were utilized for the determination of OMZ concentrations. The linear ranges for the proposed methods were 0.10–3.00 and 0.50–25.00 g mL−1 with the lowest LOD of 0.03 and 0.14 g mL−1 for iodine and DDQ, respectively. Analytical performance of the methods was statistically validated; RSD was <1.25% for the precision and <1.95% for the accuracy. The proposed methods were successfully applied to the analysis of OMZ in its dosage forms; the recovery was 98.91–100.32% ± 0.94–1.84, and was found to be comparable with that of reference method.

  20. Does treatment of gastro-esophageal reflux disease with omeprazole decrease allergic rhinitis symptoms?

    Directory of Open Access Journals (Sweden)

    Afshin Shirkani

    2014-08-01

    Full Text Available Background: Allergic rhinitis is the most common type of allergic disease among population. Its accurate treatment is very important for cutting of allergic march. On the other hand, gasteroesophageal reflux disease (GERD is one of the most common gastrointestinal problems among allergic patients mainly asthmatic cases. It might conflict treatment. Despite of asthma, a few studies have been conducted on the impact of GERD treatment on allergic rhinitis symptoms. In this study, we assessed GERD treatment and its effects on improving of allergic rhinitis patients with GERD. Materials and Methods: In a prospective cross-sectional study, March - September 2012, 103 consecutive patients with persistent moderate to severe seasonal allergic rhinitis enrolled. For allergic rhinitis patients with GERD 20 mg omeperazole once daily for 6 weeks prescribed, empirically. Conventional allergy treatment continued and finally the allergic rhinitis symptoms were assessed clinically and recorded before, 5th, 10th and 30th days of omeprazole treatment period. Results: Our study included 103 patients with seasonal allergic rhinitis who were divided into GERD (n=33, 38% and non-GERD (n=70, 68% groups with the mean age 28 and 25.7 years, respectively. The first group developed significant improvement for GERD symptoms on days 5, 10 and 30 after beginning of therapy (P=0.03. No association was found between GERD treatment and relief of allergic symptoms or TNSS improvement (P>0.05. Data analyzed by Epi info (ver 7 and SPSS software (ver 11.5, and by Chi squeare test and paired T test. P lower than 0.05 was considered as significant. Conclusion: This study showed no significant association between empirical treatment of GERD and improvement of allergic symptoms in patients with allergic rhinitis. However, further studies with a larger sample size might be needed.

  1. Development of an optimal lidocaine infusion strategy for neonatal seizures.

    Science.gov (United States)

    Malingré, Mirte M; Van Rooij, Linda G M; Rademaker, Carin M A; Toet, Mona C; Ververs, Tessa F F T; van Kesteren, Charlotte; de Vries, Linda S

    2006-09-01

    Lidocaine is an effective drug for the treatment of neonatal convulsions not responding to traditional anticonvulsant therapy. However, one of the side-effects is a risk of cardiac arrhythmias. The aim of this study was to develop an optimal dosing strategy with minimal risk of cardiac arrhythmias. As a first step, we studied 20 neonates during routine treatment of neonatal seizures with lidocaine. All were given a loading dose of 2 mg/kg in 10 min, followed by the continuous infusion of 6 mg/kg per hour for 12 h, 4 mg/kg per hour for 12 h and finally 2 mg/kg per hour for 12 h. Effectiveness, cardiac toxicity and lidocaine plasma concentrations were then determined. No cardiac arrhythmias were observed, and lidocaine was effective in 76% of the treatments. In most of the treatments (13 out of 20) maximal lidocaine plasma concentrations were >9 mg/L. Plasma levels >9 mg/L have been related to cardiac toxicity when used as an anti-arrhythmic drug in adults. It was of interest that all preterm infants showed high lidocaine plasma levels. Secondly, we developed the optimal dosing regimen, which was defined as an infusion regimen at which maximal lidocaine plasma concentrations are neonates (16 treatments) were studied. No cardiac arrhythmias were observed, and lidocaine was effective in 78% of the treatments. In most of the treatments (11 out of 16) maximal lidocaine plasma concentrations were arrhythmias and appears to be as effective in term infants. For preterm infants the optimal regimen needs to be determined.

  2. Treatment of metastatic renal cell carcinoma by continuous intravenous infusion of recombinant interleukin-2

    DEFF Research Database (Denmark)

    Geertsen, P F; Hermann, G G; von der Maase, H

    1992-01-01

    PURPOSE: A single-center phase II study was performed to evaluate the efficacy of recombinant interleukin-2 (rIL-2) administered by continuous infusion to patients with metastatic renal cell carcinoma (RCC). PATIENTS AND METHODS: Thirty-one patients with RCC were entered onto the study. rIL-2...... (Proleukin; Eurocetus Corp, Amsterdam, The Netherlands) was administered intravenously in a dose of 18 x 10(6) IU/m2 per 24 hours. A maximum of two induction cycles and four maintenance cycles were given. Each induction cycle consisted of two rIL-2 infusion periods of 120 hours and 108 hours duration......, respectively; these were separated by a 6-day rest period. Each maintenance cycle consisted of a 120 hours rIL-2 infusion period. RESULTS: Six of 30 assessable patients (20%) responded; two (7%) with a complete response (CR) and four (13%) with a partial response (PR). The response duration for patients...

  3. The effects of norepinephrine infusion on oxygen consumption in a patient with septic shock.

    Science.gov (United States)

    Bouffard, Y; Tissot, S; Viale, J P; Delafosse, B; Annat, G; Bachmann, P; Motin, J

    1990-01-01

    A 65-year-old man developed postsurgical septic shock, unresponsive to plasma volume expansion and administration of dopamine and dobutamine. A continuous norepinephrine infusion was then started and the dose increased to 0.62 micrograms.kg-1.min-1 until the mean arterial pressure was 70 mmHg. Prior to and during the norepinephrine infusion, oxygen consumption was continuously measured with a mass spectrometer system. There was a parallel increase in mean arterial pressure and oxygen consumption (+ 35%). There was also an increase in cardiac index and oxygen delivery. Systemic vascular resistance was only transiently increased. In this case with septic shock, norepinephrine infusion improved hemodynamic variables with an associated increase in oxygen consumption.

  4. A randomised controlled trial of two infusion rates to decrease reactions to antivenom.

    Directory of Open Access Journals (Sweden)

    Geoffrey K Isbister

    Full Text Available BACKGROUND: Snake envenoming is a major clinical problem in Sri Lanka, with an estimated 40,000 bites annually. Antivenom is only available from India and there is a high rate of systemic hypersensitivity reactions. This study aimed to investigate whether the rate of infusion of antivenom reduced the frequency of severe systemic hypersensitivity reactions. METHODS AND FINDINGS: This was a randomized comparison trial of two infusion rates of antivenom for treatment of non-pregnant adult patients (>14 y with snake envenoming in Sri Lanka. Snake identification was by patient or hospital examination of dead snakes when available and confirmed by enzyme-immunoassay for Russell's viper envenoming. Patients were blindly allocated in a 11 randomisation schedule to receive antivenom either as a 20 minute infusion (rapid or a two hour infusion (slow. The primary outcome was the proportion with severe systemic hypersensitivity reactions (grade 3 by Brown grading system within 4 hours of commencement of antivenom. Secondary outcomes included the proportion with mild/moderate hypersensitivity reactions and repeat antivenom doses. Of 1004 patients with suspected snakebites, 247 patients received antivenom. 49 patients were excluded or not recruited leaving 104 patients allocated to the rapid antivenom infusion and 94 to the slow antivenom infusion. The median actual duration of antivenom infusion in the rapid group was 20 min (Interquartile range[IQR]:20-25 min versus 120 min (IQR:75-120 min in the slow group. There was no difference in severe systemic hypersensitivity reactions between those given rapid and slow infusions (32% vs. 35%; difference 3%; 95%CI:-10% to +17%;p = 0.65. The frequency of mild/moderate reactions was also similar. Similar numbers of patients in each arm received further doses of antivenom (30/104 vs. 23/94. CONCLUSIONS: A slower infusion rate would not reduce the rate of severe systemic hypersensitivity reactions from current high

  5. Omeprazole preserves the RER in chief cells and enhances re-epithelialization of parietal cells with SOD and AQP-4 up-regulation in ethanol-induced gastritis rats.

    Science.gov (United States)

    Kengkoom, Kanchana; Tirawanchai, Napatara; Angkhasirisap, Wannee; Ampawong, Sumate

    2017-12-01

    Gastric mucosal cells, particularly parietal and chief cells, are usually affected by exogenous, and endogenous stimuli-induced gastritis. The integrity of these cells and their alterations are involved in the pathogenesis of numerous gastric disorders. Omeprazole, a gastric acid secretion blocker, is commonly used for gastrointestinal diseases due to its antioxidative stress and anti-inflammatory properties. Little is known regarding how omeprazole modulates the re-epithelialized effect on gastric mucosal cells associated with gastrointestinal disorders. The present study aimed to determine whether omeprazole attenuates parietal and chief cell damage in association with its antioxidative property. An in vivo ethanol-induced gastritis rat model was used. Histopathological, scanning and transmission electron microscopic, and immunohistochemical studies were performed. The results revealed that omeprazole improved the gastric mucosal surface, and reduced the severity of mucosal inflammation and hemorrhaging. Notably, ethanol-induced gastritis caused dysmorphic rough endoplasmic reticulum (RER) in chief cells, which was accompanied by mitochondrial swelling. This alteration was modulated by omeprazole due to its antioxidant effect characterized by upregulation of superoxide dismutase in gastric mucosal cells. In addition, expression of aquaporin-4 was increased in the omeprazole treatment group, which may be due to the expansion of regenerative parietal cells and acid suppression. The results of the present study suggest that omeprazole preserves the RER in chief cells and enhances parietal cell regeneration through its antioxidative property by exerting anti-inflammatory effects.

  6. Infusion reactions associated with rituximab treatment for childhood-onset complicated nephrotic syndrome.

    Science.gov (United States)

    Kamei, Koichi; Ogura, Masao; Sato, Mai; Ito, Shuichi; Ishikura, Kenji

    2018-02-09

    Infusion reaction (IR) is defined as an adverse event within 24 h after monoclonal antibody infusion. In non-Hodgkin lymphoma, IR incidence following rituximab treatment is high (77-80%), but there are no data in complicated nephrotic syndrome. Records of rituximab infusions in patients with complicated nephrotic syndrome between February 2006 and December 2014 at the National Center for Child Health and Development were reviewed. Rituximab was administered at doses of 375 mg/m 2 . The severity of IR was evaluated using the Common Terminology Criteria for Adverse Events ver. 4.0. For 309 rituximab infusions in 159 patients (male, 110; median age, 12 years), IR was observed in 165 infusions (53.4%). Respiratory symptoms were most common (66% of all events). Ninety-five percent of the IR was observed within 3 h after rituximab infusion initiation. Sixty-eight percent of the events were classified as grade 1 and others classified as grade 2. Only 18% required medical intervention. CD20 cell count in patients with IR was significantly higher than in patients without IR. Incidence of IR was similar in subsequent rituximab treatment after B-cell recovery. Patients who experienced IR at first rituximab treatment were more likely to experience recurrent IR with subsequent treatments compared to those not having IR at initial treatment (odds ratio 3.64; p nephrotic syndrome, respiratory symptoms were the major type of IR, mostly observed within 3 h of infusion. Incidence of IR was lower and its severity milder in patients with complicated nephrotic syndrome than those with lymphoma.

  7. Evaluation of the pharmacokinetics and safety of single and multiple ceftaroline fosamil infusions in healthy Chinese and Western subjects.

    Science.gov (United States)

    Yang, Li; Sunzel, Maria; Xu, Peng; Edeki, Timi; Wilson, David; Li, Jianguo; Li, Haiyan

    2015-08-01

    Two phase I studies in healthy Chinese (NCT01458743) and Western (NCT01612507) subjects evaluated the pharmacokinetics (PK) and safety of single and multiple ceftaroline fosamil 600 mg infusions administered every 8 or 12 hours (q8h or q12h). Each study enrolled subjects sequentially into 1 of 2 cohorts (cohort 1: 60-minute infusions; cohort 2: 120-minute infusions). All subjects in the Chinese (n = 26) study received open label ceftaroline fosamil; in the Western study, subjects (n = 41) in each cohort were randomized 3 : 1 to ceftaroline fosamil or placebo infusions. Single infusions were administered on days 1 and 8. On days 2 - 7 (3 - 7 for Chinese study, cohort 1) subjects received q12h or q8h infusions. Plasma and urine were collected on days 1 and 8 for PK analysis. Ceftaroline PK was linear and time-independent following single and multiple doses of ceftaroline fosamil. The magnitude and timing of peak plasma concentrations of ceftaroline (active metabolite), ceftaroline fosamil (prodrug), and ceftaroline M-1 (inactive metabolite) varied according to the ceftaroline fosamil dosing schedule (q12h or q8h) and infusion duration (60 minutes or 120 minutes), but overall plasma ceftaroline exposures within the respective dosing intervals were broadly similar across cohorts. The most frequent adverse events were rash/drug eruption, most of which were of mild-moderate intensity and considered related to treatment. Ceftaroline PK was broadly similar in healthy Chinese and Western subjects receiving equivalent dose regimens. The tolerability profile of ceftaroline fosamil in Chinese and Western subjects was consistent with previous clinical trials.

  8. Effects of intra-arterial infusion therapy or systemic chemotherapy with docetaxel for VX2 tumor in rabbit hind limb

    International Nuclear Information System (INIS)

    Qian Yuanxin; Wu Xiaomei; He Miao; Liu Tao; Deng Duo

    2010-01-01

    Objective: To discuss the efficacy and safety of intra-arterial infusion therapy with docetaxel. Methods: Animal model of VX2 tumor in rabbit hind limb was set up. Intra-arterial infusion therapy or systemic chemotherapy with docetaxel was performed. Concentrations of docetaxel in VX2 tumor, wall of stomach, liver, kidney and plasma of rabbits with VX2 tumors in hind limbs were determined. Difference of drug concentrations between intra-arterial infusion therapy and systemic chemotherapy was compared using Student t-test. Results: Concentrations of docetaxel in VX2 tumor and wall of stomach of rabbits with intra-arterial infusion therapy were significantly higher than those with systemic chemotherapy (p<0.05). The drug concentration in VX2 tumor of rabbits with intra-arterial infusion was 14 times higher than that with systemic chemotherapy. Concentration of docetaxel in plasma of rabbits with intra-arterial infusion therapy was not significantly lower than that with systemic chemotherapy (P<0.05). Conclusion: Intra-arterial infusion therapy with docetaxel for tumor is effective. However, there is increased risk of toxicity and the dose should adjusted accordingly. (authors)

  9. Home infusion: overcoming the barriers to entry.

    Science.gov (United States)

    Franklin, David M

    2010-01-01

    The field of pharmacy service is evolving rapidly, as is the delivery of healthcare in general. From patients with infectious diseases dying because there was nothing available to fight the infections, to the involvement of an episodic-based model of care with patients traversing inpatient- and outpatient-based delivery systems, to the new frontier of chronic care and with supports such as the one by the Centers for Disease Control that hospital-acquired infections are killing about 100,000 Americans every year, the home infusion business has become a major alternative to in-hospital treatment. This article discusses the barriers to entry into the home infusion business and assists in the evaluation of a home infusion reimbursement organization.

  10. Design of Infusion Schemes for Neuroreceptor Imaging

    DEFF Research Database (Denmark)

    Feng, Ling; Svarer, Claus; Madsen, Karine

    2016-01-01

    for bolus infusion (BI) or programmed infusion (PI) experiments. Steady-state quantitative measurements can be made with one short scan and venous blood samples. The GABAA receptor ligand [(11)C]Flumazenil (FMZ) was chosen for this purpose, as it lacks a suitable reference region. Methods. Five bolus [(11)C...... state was attained within 40 min, which was 8 min earlier than the optimal BI (B/I ratio = 55 min). Conclusions. The system can design both BI and PI schemes to attain steady state rapidly. For example, subjects can be [(11)C]FMZ-PET scanned after 40 min of tracer infusion for 40 min with venous...

  11. Forearm metabolism during infusion of adrenaline

    DEFF Research Database (Denmark)

    Simonsen, L; Stefl, B; Bülow, J

    2000-01-01

    Human skeletal muscle metabolism is often investigated by measurements of substrate fluxes across the forearm. To evaluate whether the two forearms give the same metabolic information, nine healthy subjects were studied in the fasted state and during infusion of adrenaline. Both arms were...... catheterized in a cubital vein in the retrograde direction. A femoral artery was catheterized for blood sampling, and a femoral vein for infusion of adrenaline. Forearm blood flow was measured by venous occlusion strain-gauge plethysmography. Forearm subcutaneous adipose tissue blood flow was measured...... by the local 133Xe washout method. Metabolic fluxes were calculated as the product of forearm blood flow and a-v differences of metabolite concentrations. After baseline measurements, adrenaline was infused at a rate of 0.3 nmol kg-1 min-1. No difference in the metabolic information obtained in the fasting...

  12. Supramolecular separation mechanism of pentafluorophenyl column using ibuprofen and omeprazole as markers: LC-MS and simulation study.

    Science.gov (United States)

    Hussain, Afzal; AlAjmi, Mohamed F; Ali, Imran

    2018-02-12

    The pentafluorophenyl (PFP) column is emerging as a new advancement in separation science to analyze a wide range of analytes and, thus, its separation mechanism at supramolecular level is significant. We developed a mechanism for the separation of ibuprofen and omeprazole using different combinations (ranging from 50:50 to 60:40) of water-acetonitrile containing 0.1% formic acid as the mobile phase. The column used was Waters Acquity UPLC HSS PFP (75 × 2.1 mm, 1.8 μm). The reverse order of elution was observed in different combinations of the mobile phases. The docking study indicated hydrogen bonding between ibuprofen and PFP stationary phase (binding energy was -11.30 kJ/mol). Separation at PFP stationary phase is controlled by hydrogen bonding along with π-π interactions. This stationary phase may be used to analyze both aromatic and aliphatic analytes. The developed mechanism will be useful to separate various analytes by considering the possible interactions, leading to saving of energy, time and money. In addition, this work will be highly useful in preparative chromatography where separation is the major problem at a large scale. Moreover, the developed LC-MS-QTOF method may be used to analyze ibuprofen and omeprazole in an unknown sample owing to the low value of detection limits. Copyright © 2018 John Wiley & Sons, Ltd.

  13. Effectiveness differences of ranitidine and omeprazole in prevention of stress ulcer and its effect on pneumonia occurrence and outcome of acute stroke patients

    Science.gov (United States)

    Batubara, C. A.; Ritarwan, K.; Rambe, A. S.

    2018-03-01

    Stress ulcer is one ofacute stroke complications. Giving ranitidine or omeprazole may prevent stress ulcer, but may increase the occurrence of pneumonia. Thus, it will affect the outcome of acute stroke. The method was experimental with a randomized control-group pretest - posttest design. This study divided the subjects into two groups, ranitidine 300mg and omeprazole 20mg group.We observed the patients whether stress ulcer or pneumonia occurred during hospitalization. Then, we measured the outcome by the National Institutes of Health Stroke Scaleand modified Rankin Scale. There were 32 subjects in this study. Only 1 (3.1%) subject suffered stress ulcer, and 3 (3.1%) suffered pneumonia in ranitidine group. Moreover, 2 (6.2%) subjects suffered pneumonia in omeprazole group. The differences were not significant between the two groups (p = 0.31 and p = 0.54). There was no significant effect and difference effect on the administration of both medications to the outcome at day 14. These results indicate that ranitidine and omeprazole have anequal effectiveness in the prevention of stress ulcer and also have equal effect on the occurrence of pneumonia, and both have no effect on the outcome of acute stroke patients.

  14. A Pharmacoeconomic Comparison of the Efficacy and costs of Pantoprazole and Omeprazole for the Treatment of Peptic Ulcer or Gastroesophageal Reflux Disease in the Netherlands

    NARCIS (Netherlands)

    van Hout, BA; Klok, RM; Brouwers, JRBJ; Postma, MJ

    Background: The focus of treatment of patients with peptic ulcer or gastroesophageal reflux disease has changed during the last 15 years, with a shift from histamine(2)-receptor antagonists to proton-pump inhibitors (PPIs). From 1993 to 2000, expenditures for omeprazole (90% of total market share of

  15. Investigating the presence of omeprazole in waters by liquid chromatography coupled to low and high resolution mass spectrometry. (I) Degradation experiments.

    NARCIS (Netherlands)

    Boix, C; Ibáñez, M.; Zamora, T.; Sancho, J.V.; Niessen, W.M.A.; Hernández, F.

    2013-01-01

    Omeprazole is one of the most consumed pharmaceuticals around the world. However, this compound is scarcely detected in urban wastewater and surface water. The absence of this pharmaceutical in the aquatic ecosystem might be due to its degradation in wastewater treatment plants, as well as in

  16. Randomized trial of omeprazole and clarithromycin combined with either metronidazole or amoxycillin in patients with metronidazole-resistant or -susceptible Helicobacter pylori strains

    NARCIS (Netherlands)

    Houben, M. H.; Hensen, E. F.; Rauws, E. A.; Hulst, R. W.; Hoff, B. W.; van der Ende, A.; ten Kate, F. J.; Tytgat, G. N.

    1999-01-01

    The impact of metronidazole resistance on the efficacy of proton pump inhibitor based triple therapies remains unclear. To study whether metronidazole resistance affects Helicobacter pylori eradication rates in patients treated for 1 week with either omeprazole 20 mg b.d., metronidazole 400 mg b.d.

  17. Urine metabolic ratio of omeprazole in relation to CYP2C19 polymorphisms in Russian peptic ulcer patients.

    Science.gov (United States)

    Denisenko, Natalia P; Sychev, Dmitriy A; Sizova, Zhanna M; Smirnov, Valeriy V; Ryzhikova, Kristina A; Sozaeva, Zhannet A; Grishina, Elena A

    2017-01-01

    CYP2C19 is known to be the main enzyme of biotransformation of proton pump inhibitors (PPIs), whereas the CYP2C19 gene is highly polymorphic. Genotyping and phenotyping together represent more reliable data about patient's CYP2C19 activity. The aim of the study was to investigate the applicability of urine metabolic ratio of omeprazole for CYP2C19 phenotyping in Russian peptic ulcer patients with different CYP2C19 genotypes. A total of 59 patients (19 men and 40 women) aged 18-91 years (mean age 53.5±15.1 years) from four Moscow clinics who were diagnosed with an endoscopically and histologically proven peptic ulcer or had a history of endoscopically and histologically proven ulcers in the past were recruited. Peripheral venous blood (6 mL) was collected for DNA extraction, and real-time polymerase chain reaction was performed for the analysis of CYP2C19*2 G681A (rs4244285), CYP2C19*3 G636A (rs4986893) and CYP2C19*17 C-806T (rs12248560) polymorphisms. Urine samples of patients were collected in the morning between 6 am and 9 am, before food or drug intake, after at least 3 days of twice daily (b.i.d.) omeprazole intake. Omeprazole and 5-hydroxyomeprazole concentrations in the urine were measured using high-performance liquid chromatography with mass spectrometry. Of the 59 patients, there were 27 (45.8%) extensive metabolizers (EMs; CYP2C19*1/*1), 16 (27.1%) ultrarapid metabolizers (UMs; CYP2C19*1/*17, CYP2C19*17/*17), 14 (23.7%) intermediate metabolizers (IMs; CYP2C19*1/*2, CYP2C19*2/*17, CYP2C19*3/*17) and two (3.4%) poor metabolizers (PMs; CYP2C19*2/*2). Median metabolic ratio (25%-75% percentiles) were 1.03 (0.69-1.36) for EMs, 1.95 (1.33-2.68) for UMs, 1.40 (0.78-2.13) for IMs+PMs and 1.26 (0.82-1.99) for the whole sample. A statistically significant difference in metabolic ratio (Mann-Whitney U test) was found between UMs and EMs ( p =0.001) and in the multiple comparison Kruskal-Wallis test ( p =0.005). We found a connection between particular CYP2C19

  18. Urine metabolic ratio of omeprazole in relation to CYP2C19 polymorphisms in Russian peptic ulcer patients

    Directory of Open Access Journals (Sweden)

    Denisenko NP

    2017-09-01

    Full Text Available Natalia P Denisenko,1–3 Dmitriy A Sychev,2 Zhanna M Sizova,3 Valeriy V Smirnov,4,5 Kristina A Ryzhikova,1 Zhannet A Sozaeva,1 Elena A Grishina1 1Research Center, Russian Medical Academy of Continuous Professional Education, Ministry of Healthcare, Moscow, Russia; 2Department of Clinical Pharmacology and Therapy, Russian Medical Academy of Continuous Professional Education, Ministry of Healthcare, Moscow, Russia; 3Department of Social Expertise, Urgent and Outpatient Therapy, First Moscow State Medical University (Sechenov University, Ministry of Healthcare, Moscow, Russia; 4Department of Pharmaceutical and Toxicological Chemistry, First Moscow State Medical University (Sechenov University, Ministry of Healthcare, Moscow, Russia; 5Laboratory of Clinical Pharmacology, National Research Centre, Institute of Immunology, Federal Medical Biological Agency, Moscow, Russia Background: CYP2C19 is known to be the main enzyme of biotransformation of proton pump inhibitors (PPIs, whereas the CYP2C19 gene is highly polymorphic. Genotyping and phenotyping together represent more reliable data about patient’s CYP2C19 activity.Purpose: The aim of the study was to investigate the applicability of urine metabolic ratio of omeprazole for CYP2C19 phenotyping in Russian peptic ulcer patients with different CYP2C19 genotypes.Patients and methods: A total of 59 patients (19 men and 40 women aged 18–91 years (mean age 53.5±15.1 years from four Moscow clinics who were diagnosed with an endoscopically and histologically proven peptic ulcer or had a history of endoscopically and histologically proven ulcers in the past were recruited. Peripheral venous blood (6 mL was collected for DNA extraction, and real-time polymerase chain reaction was performed for the analysis of CYP2C19*2G681A (rs4244285, CYP2C19*3G636A (rs4986893 and CYP2C19*17C-806T (rs12248560 polymorphisms. Urine samples of patients were collected in the morning between 6 am and 9 am, before food or

  19. Costs of Providing Infusion Therapy for Rheumatoid Arthritis in a Hospital-based Infusion Center Setting.

    Science.gov (United States)

    Schmier, Jordana; Ogden, Kristine; Nickman, Nancy; Halpern, Michael T; Cifaldi, Mary; Ganguli, Arijit; Bao, Yanjun; Garg, Vishvas

    2017-08-01

    Many hospital-based infusion centers treat patients with rheumatoid arthritis (RA) with intravenous biologic agents, yet may have a limited understanding of the overall costs of infusion in this setting. The purposes of this study were to conduct a microcosting analysis from a hospital perspective and to develop a model using an activity-based costing approach for estimating costs associated with the provision of hospital-based infusion services (preparation, administration, and follow-up) in the United States for maintenance treatment of moderate to severe RA. A spreadsheet-based model was developed. Inputs included hourly wages, time spent providing care, supply/overhead costs, laboratory testing, infusion center size, and practice pattern information. Base-case values were derived from data from surveys, published studies, standard cost sources, and expert opinion. Costs are presented in year-2017 US dollars. The base case modeled a hospital infusion center serving patients with RA treated with abatacept, tocilizumab, infliximab, or rituximab. Estimated overall costs of infusions per patient per year were $36,663 (rituximab), $36,821 (tocilizumab), $44,973 (infliximab), and $46,532 (abatacept). Of all therapies, the biologic agents represented the greatest share of overall costs, ranging from 87% to $91% of overall costs per year. Excluding infusion drug costs, labor accounted for 53% to 57% of infusion costs. Biologic agents represented the highest single cost associated with RA infusion care; however, personnel, supplies, and overhead costs also contributed substantially to overall costs (8%-16%). This model may provide a helpful and adaptable framework for use by hospitals in informing decision making about services offered and their associated financial implications. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  20. Epidural blood flow and regression of sensory analgesia during continuous postoperative epidural infusion of bupivacaine

    DEFF Research Database (Denmark)

    Mogensen, T; Højgaard, L; Scott, N B

    1988-01-01

    Epidural blood flow was measured in seven patients undergoing elective abdominal surgery during combined lumbar epidural and general anesthesia. After an initial dose of 20 ml plain bupivacaine 0.5%, a continuous epidural infusion of bupivacaine 0.5% (8 ml/hr) was given for 16 hours for postopera......Epidural blood flow was measured in seven patients undergoing elective abdominal surgery during combined lumbar epidural and general anesthesia. After an initial dose of 20 ml plain bupivacaine 0.5%, a continuous epidural infusion of bupivacaine 0.5% (8 ml/hr) was given for 16 hours...... surgery, and 8, 12, and 16 hours later during the continuous infusion. Initial blood flow was 6.0 +/- 0.7 ml/min per 100 g tissue (mean +/- SEM). After epidural bupivacaine, blood flow increased in all seven patients to 7.4 +/- 0.7 ml (P less than 0.02). Initial level of sensory analgesia was T4.5 +/- 0...... than 0.03) in the other five patients as the level of sensory analgesia regressed postoperatively. These data suggest that changes in epidural blood flow during continuous epidural infusion of bupivacaine, and thus changes in rates of vascular absorption of bupivacaine from the epidural space, may...

  1. Growth and descent of the testes in infants with hypogonadotropic hypogonadism receiving subcutaneous gonadotropin infusion.

    Science.gov (United States)

    Lambert, Anne-Sophie; Bougneres, Pierre

    2016-01-01

    One third of infants with congenital hypogonadotropic hypogonadism (CHH) are said to have micropenis and/or bilateral or unilateral cryptorchidism leading many of them to orchiopexy. Our previous study in two patients suggests that prolonged subcutaneous infusion of large doses of gonadotropins might normalize testicular function and growth. To confirm the effects of early and prolonged subcutaneous infusion of large doses of gonadotropins on growth and descent of the testes. Eight boys with CHH, aged 0.25-11 months. Testes were non-palpable in 5 or in high scrotal position in 3. CHH was isolated in 5 infants and part of a syndrome of combined pituitary hormonal deficits in the 3 others. In response to gonadotropin infusion, mean levels of testicular hormones were normalized. Complete testis descent occurred in 6 patients. Partial descent occurred in 2. Testes re-ascended in 1 patient. Testes and penis gained normal dimensions in all cases. Subcutaneous gonadotropin infusion seems able to induce testis descent in a large proportion of infants with CHH. If confirmed, this may allow patients to avoid testes surgery but studies in larger series are needed to evaluate the benefits of this treatment versus traditional orchiopexy.

  2. Intrathecal Trialing of Continuous Infusion Combination Therapy With Hydromorphone and Bupivacaine in Failed Back Surgery Patients.

    Science.gov (United States)

    Galica, Ryan J; Hayek, Salim M; Veizi, Elias; McEwan, Matthew T; Katta, Sivakanth; Ali, Omar; Aziz, Nida; Sondhi, Nidhi

    2017-12-05

    Intrathecal (IT) trial is a prognostic interventional pain management procedure employed to determine the potential success of treating intractable pain with an implantable infusion device system. There is a dearth of data regarding trials with continuous infusion of combination therapy (e.g. opioid combined with local anesthetic). The objective of the this study was to determine the overall outcomes of continuous infusion IT trials and factors influencing long-term success of IT therapy in patients with chronic intractable pain post-laminectomy. This is a retrospective analysis of all patients with lumbar failed back surgery syndrome (FBSS) who were trialed with a combination of hydromorphone and bupivacaine with a temporary externalized IT catheter from March 2007 to June 2014. From a cohort of 62 patients fulfilling the inclusion criteria, 54 (87.10%) patients had successful IT trials. No significant differences were found between successful and failed trial patients with regards to age, sex, pre-trial pain numeric rating scale scores, pre-trial morphine equivalent daily dose, or trial dosages. Significant positive correlations were found between pretrial oral opioid intake and end of trial hydromorphone dose and hydromorphone dose escalation at 12 months and 24 months. Patients with refractory low back pain due to FBSS who underwent successful combination IT trial with hydromorphone and bupivacaine infused through a temporary IT catheter had significantly improved pain intensity scores following permanent implant. Higher pre-trial MEDD was correlated with higher trial and post-implant opioid doses and higher rates of opioid dose escalation post-implant. © 2017 International Neuromodulation Society.

  3. Effect of steel and teflon infusion catheters on subcutaneous adipose tissue blood flow and infusion counter pressure in humans

    DEFF Research Database (Denmark)

    Højbjerre, Lise; Skov-Jensen, Camilla; Kaastrup, Peter

    2009-01-01

    BACKGROUND: Subcutaneous tissue is an important target for drug deposition or infusion. A local trauma may induce alterations in local microcirculation and diffusion barriers with consequences for drug bioavailability. We examined the influence of infusion catheters' wear time on local...... microcirculation and infusion counter pressure. METHODS: One steel catheter and one Teflon (Dupont, Wilmington, DE) catheter were inserted in subcutaneous, abdominal adipose tissue (SCAAT) in 10 healthy, lean men. The catheters were infused with isotonic saline at a rate of 10 microL/h for 48 h. Another steel...... catheter and a Teflon catheter were inserted contralateral to the previous catheters after 48 h. The infusion counter pressure was measured during a basal infusion rate followed by a bolus infusion. The measurements during a basal rate infusion were repeated after the bolus infusion. Adipose tissue blood...

  4. Thermodynamic models for determination of the solubility of omeprazole in pure and mixture organic solvents from T = (278.15 to 333.15) K

    International Nuclear Information System (INIS)

    Hu, Yonghong; Wu, Gang; Gu, Pengfei; Yang, Wenge; Wang, Chunxiao; Ding, Zhiwen; Cao, Yang

    2016-01-01

    Highlights: • The solubility increased with increasing temperature. • The data were fitted using the modified Apelblat equation and other models. • The Gibbs energy, enthalpy and entropy were calculated by the van’t Hoff analysis. - Abstract: Data on corresponding (solid + liquid) equilibrium of omeprazole in different solvents are essential for a preliminary study of industrial applications. In this paper, the (solid + liquid) equilibrium of omeprazole in water, methanol, ethanol, 1-butanol, acetonitrile, acetone, ethyl acetate, tetrahydrofuran pure solvents and (tetrahydrofuran + ethyl acetate) mixture solvents were explored within the temperatures from 278.15 K to 333.15 K under atmosphere pressure. For the temperature range investigated, the solubility of omeprazole in the solvents increased with increasing temperature. From (278.15 to 333.15) K, the solubility of omeprazole in tetrahydrofuran is superior to other selected pure solvents. The modified Apelblat model, the Buchowski–Ksiazaczak λh model, and the ideal model were adopted to describe and predict the change tendency of solubility. Computational results showed that the modified Apelblat model has advantages than the other two models. Numerical values of the solubility were fitted using a modified Apelblat equation, a variant of the combined nearly ideal binary solvent/Redich–Kister (CNIBS/R–K) model and Jouyban–Acree model in (tetrahydrofuran + ethyl acetate) binary solvent mixture. Computational results showed that the CNIBS/R–K model is superior to the other equations. In addition, the calculated thermodynamic parameters indicate that in each solvent studied the dissolution of omeprazole is endothermic, non-spontaneous and is an entropy-driven process.

  5. Physiological and Metabolic Responses Triggered by Omeprazole Improve Tomato Plant Tolerance to NaCl Stress.

    Science.gov (United States)

    Rouphael, Youssef; Raimondi, Giampaolo; Lucini, Luigi; Carillo, Petronia; Kyriacou, Marios C; Colla, Giuseppe; Cirillo, Valerio; Pannico, Antonio; El-Nakhel, Christophe; De Pascale, Stefania

    2018-01-01

    Interest in the role of small bioactive molecules (< 500 Da) in plants is on the rise, compelled by plant scientists' attempt to unravel their mode of action implicated in stimulating growth and enhancing tolerance to environmental stressors. The current study aimed at elucidating the morphological, physiological and metabolomic changes occurring in greenhouse tomato (cv. Seny) treated with omeprazole (OMP), a benzimidazole inhibitor of animal proton pumps. The OMP was applied at three rates (0, 10, or 100 μM) as substrate drench for tomato plants grown under nonsaline (control) or saline conditions sustained by nutrient solutions of 1 or 75 mM NaCl, respectively. Increasing NaCl concentration from 1 to 75 mM decreased the tomato shoot dry weight by 49% in the 0 μM OMP treatment, whereas the reduction was not significant at 10 or 100 μM of OMP. Treatment of salinized (75 mM NaCl) tomato plants with 10 and especially 100 μM OMP decreased Na + and Cl - while it increased Ca 2+ concentration in the leaves. However, OMP was not strictly involved in ion homeostasis since the K + to Na + ratio did not increase under combined salinity and OMP treatment. OMP increased root dry weight, root morphological characteristics (total length and surface), transpiration, and net photosynthetic rate independently of salinity. Metabolic profiling of leaves through UHPLC liquid chromatography coupled to quadrupole-time-of-flight mass spectrometry facilitated identification of the reprogramming of a wide range of metabolites in response to OMP treatment. Hormonal changes involved an increase in ABA, decrease in auxins and cytokinin, and a tendency for GA down accumulation. Cutin biosynthesis, alteration of membrane lipids and heightened radical scavenging ability related to the accumulation of phenolics and carotenoids were observed. Several other stress-related compounds, such as polyamine conjugates, alkaloids and sesquiterpene lactones, were altered in response to OMP. Although a

  6. Physiological and Metabolic Responses Triggered by Omeprazole Improve Tomato Plant Tolerance to NaCl Stress

    Directory of Open Access Journals (Sweden)

    Youssef Rouphael

    2018-02-01

    Full Text Available Interest in the role of small bioactive molecules (< 500 Da in plants is on the rise, compelled by plant scientists' attempt to unravel their mode of action implicated in stimulating growth and enhancing tolerance to environmental stressors. The current study aimed at elucidating the morphological, physiological and metabolomic changes occurring in greenhouse tomato (cv. Seny treated with omeprazole (OMP, a benzimidazole inhibitor of animal proton pumps. The OMP was applied at three rates (0, 10, or 100 μM as substrate drench for tomato plants grown under nonsaline (control or saline conditions sustained by nutrient solutions of 1 or 75 mM NaCl, respectively. Increasing NaCl concentration from 1 to 75 mM decreased the tomato shoot dry weight by 49% in the 0 μM OMP treatment, whereas the reduction was not significant at 10 or 100 μM of OMP. Treatment of salinized (75 mM NaCl tomato plants with 10 and especially 100 μM OMP decreased Na+ and Cl− while it increased Ca2+ concentration in the leaves. However, OMP was not strictly involved in ion homeostasis since the K+ to Na+ ratio did not increase under combined salinity and OMP treatment. OMP increased root dry weight, root morphological characteristics (total length and surface, transpiration, and net photosynthetic rate independently of salinity. Metabolic profiling of leaves through UHPLC liquid chromatography coupled to quadrupole-time-of-flight mass spectrometry facilitated identification of the reprogramming of a wide range of metabolites in response to OMP treatment. Hormonal changes involved an increase in ABA, decrease in auxins and cytokinin, and a tendency for GA down accumulation. Cutin biosynthesis, alteration of membrane lipids and heightened radical scavenging ability related to the accumulation of phenolics and carotenoids were observed. Several other stress-related compounds, such as polyamine conjugates, alkaloids and sesquiterpene lactones, were altered in response to OMP

  7. Evaluation of propylene glycol and glycerol infusions as treatments for ketosis in dairy cows.

    Science.gov (United States)

    Piantoni, P; Allen, M S

    2015-08-01

    vs. 6.58min×μIU/mL) compared with G, and tended to increase insulin AUC compared with 2G. Propylene glycol was not different from GPG for glucose, insulin, or BHBA responses. Propylene glycol decreased plasma BHBA concentration (-10.3 vs. -4.21mg/dL) and increased BHBA AUC (-1,578 vs. -1.42min ×mg/dL) compared with G, but not compared with 2G. In general, and compared with G, GPG decreased plasma NEFA concentrations after infusions and PG decreased plasma NEFA concentrations early but not late after infusions. We conclude that a 300-mL dose of PG is more effective at increasing plasma glucose concentration than G and at least as effective as 600mL of G or a combination of G and PG when administered in the cranial reticulorumen. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  8. Standard drug concentrations and smart-pump technology reduce continuous-medication-infusion errors in pediatric patients.

    Science.gov (United States)

    Larsen, Gitte Y; Parker, Howard B; Cash, Jared; O'Connell, Mary; Grant, MaryJo C

    2005-07-01

    To determine if combining standard drug concentrations with "smart-pump" technology reduces reported medication-infusion errors. Preintervention and postintervention comparison of reported medication errors related to infusion therapies during the calendar years 2002 and 2003. A 242-bed university-affiliated tertiary pediatric hospital. Change in continuous-medication-infusion process, comprising the adoption of (1) standard drug concentrations, (2) "smart" syringe pumps, and (3) human-engineered medication labels. Comparison of reported continuous-medication-infusion errors before and after the intervention. The number of reported errors dropped by 73% for an absolute risk reduction of 3.1 to 0.8 per 1000 doses. Preparation errors that occurred in the pharmacy decreased from 0.66 to 0.16 per 1000 doses; the number of 10-fold errors in dosage decreased from 0.41 to 0.08 per 1000 doses. The use of standard drug concentrations, smart syringe pumps, and user-friendly labels reduces reported errors associated with continuous medication infusions. Standard drug concentrations can be chosen to allow most neonates to receive needed medications without concerns related to excess fluid administration.

  9. Routine saline infusion sonohysterography prior to assisted ...

    African Journals Online (AJOL)

    53.85%), 8 (30.77%) and 4 (15.38%) respectively. The average duration of the procedure was 6 minutes with a range of 4-9 minutes. Saline infusion sonohysterography is a reliable, cost effective and safe diagnostic tool in the evaluation of the ...

  10. Forearm metabolism during infusion of adrenaline

    DEFF Research Database (Denmark)

    Simonsen, L; Stefl, B; Bülow, J

    2000-01-01

    Human skeletal muscle metabolism is often investigated by measurements of substrate fluxes across the forearm. To evaluate whether the two forearms give the same metabolic information, nine healthy subjects were studied in the fasted state and during infusion of adrenaline. Both arms were cathete...

  11. Comparison of infusion pumps calibration methods

    Science.gov (United States)

    Batista, Elsa; Godinho, Isabel; do Céu Ferreira, Maria; Furtado, Andreia; Lucas, Peter; Silva, Claudia

    2017-12-01

    Nowadays, several types of infusion pump are commonly used for drug delivery, such as syringe pumps and peristaltic pumps. These instruments present different measuring features and capacities according to their use and therapeutic application. In order to ensure the metrological traceability of these flow and volume measuring equipment, it is necessary to use suitable calibration methods and standards. Two different calibration methods can be used to determine the flow error of infusion pumps. One is the gravimetric method, considered as a primary method, commonly used by National Metrology Institutes. The other calibration method, a secondary method, relies on an infusion device analyser (IDA) and is typically used by hospital maintenance offices. The suitability of the IDA calibration method was assessed by testing several infusion instruments at different flow rates using the gravimetric method. In addition, a measurement comparison between Portuguese Accredited Laboratories and hospital maintenance offices was performed under the coordination of the Portuguese Institute for Quality, the National Metrology Institute. The obtained results were directly related to the used calibration method and are presented in this paper. This work has been developed in the framework of the EURAMET projects EMRP MeDD and EMPIR 15SIP03.

  12. Effect of intravenous dexmedetomidine infusion on some ...

    African Journals Online (AJOL)

    Background: This study was designed to evaluate the effect of intravenous dexmedetomidine infusion in patients undergoing major abdominal surgery on stress response markers as plasma interleukin-6, cortisol and blood glucose level. It also assessed its effect on recovery profile and postoperative pain. Methods: Thirty ...

  13. Bronchial arterial infusion versus bronchial combined pulmonary arterial infusion for pulmonary metastatic tumors

    International Nuclear Information System (INIS)

    Dong Sheng; Dong Weihua; Jia Ningyang; Zhang Dianbo; Xiao Xiangsheng

    2008-01-01

    Objective: To evaluate the pulmonary metastatic tumor response to different ways of transcatheter arterial infusion. Methods: Thirty-five patients with pulmonary metastatic tumors were randomized divided into two groups: 15 patients with 49 lesions treated with bronchial arterial infusion (BAI) and 20 patients with 65 lesions treated with bronchial arterial infusion (BM)combined with pulmonary arterial infusion (PAI). The therapeutic response was assessed by the WHO evaluation criteria. Results: The total effective rate(CR + PR) of BAI was 65.3% (32/49), PAI + BAI was 61.5%(40/65) showing no statistical difference. The median survival time of BAI was 9 mo, BAI + PAI was 11.5 mo, demonstrating no statistical significance. Conclusions: BAI should be the primary treatment for pulmonary metastatic tumor. (authors)

  14. A Randomized Trial Comparing Seven-Day Ranitidine Bismuth Citrate and Clarithromycin Dual Therapy to Seven-Day Omeprazole, Clarithromycin and Amoxicillin Triple Therapy for the Eradication of Helicobacter pylori

    Directory of Open Access Journals (Sweden)

    Sander Veldhuyzen van Zanten

    2003-01-01

    Full Text Available OBJECTIVE: To assess Helicobacter pylori eradication after one week dual ranitidine bismuth citrate-clarithromycin (RBC-C or triple omeprazole, clarithromycin and amoxicillin (OCA therapy.

  15. Effects of dexmedetomidine infusion during spinal anesthesia on ...

    African Journals Online (AJOL)

    Effects of dexmedetomidine infusion during spinal anesthesia on hemodynamics and sedation. ... Libyan Journal of Medicine ... evaluated the effects of intravenous dexmedetomidine during spinal anesthesia on hemodynamics, respiratory rate, oxygen saturation, sedpain, and compared them with those of saline infusion.

  16. Furazolidona, tetraciclina e omeprazol: uma alternativa de baixo custo para erradicação de Helicobacter pylori em crianças Furazolidone, tetracycline and omeprazole: a low-cost alternative for Helicobacter pylori eradication in children

    Directory of Open Access Journals (Sweden)

    Rodrigo Strehl Machado

    2008-04-01

    Full Text Available OBJETIVOS: Avaliar furazolidona, tetraciclina e omeprazol como tratamento de primeira linha para Helicobacter pylori em crianças com sintomas digestivos. MÉTODOS: Ensaio clínico aberto, prospectivo e consecutivo. O estudo incluiu pacientes acima de 8 anos com dispepsia funcional, dor abdominal funcional, anormalidades histológicas graves (metaplasia intestinal, atrofia gástrica ou linfoma do tecido linfóide associado às mucosas ou úlcera péptica. A presença de H. pylori foi definida com base em exame histológico e teste da urease. O regime medicamentoso consistiu de um tratamento de 7 dias com omeprazol, tetraciclina (ou doxiciclina e furazolidona duas vezes por dia. A erradicação foi avaliada através de endoscopia digestiva alta 2 meses após o tratamento (exame histológico e teste da urease. Avaliações clínicas posteriores foram realizadas 7 dias e 2 meses após o tratamento. RESULTADOS: Foram incluídos 36 pacientes (21 meninas/15 meninos. A idade variou de 8 a 19 anos (média de 12,94+2,89 anos. Na análise por intenção de tratar (n = 36, a taxa de erradicação foi de 83,3% (IC95% 77,1-89,5, ao passo que na análise por protocolo (n = 29, foi de 89,7% (IC95% 84,6-94,7. A adesão foi melhor quando se utilizou doxiciclina, mas as taxas de sucesso foram semelhantes para as duas tetraciclinas. Não houve nenhuma variável associada à falha no tratamento. Foram relatados efeitos colaterais em 17 pacientes (47,2%, principalmente dor abdominal (11/30,5%, náusea (sete/19,4% e vômitos (cinco/13,9%. CONCLUSÃO: A terapia tripla com furazolidona e tetraciclina é uma alternativa de baixo custo para o tratamento da infecção pelo H. pylori.OBJECTIVE: To evaluate furazolidone, tetracycline and omeprazole as first line therapy for Helicobacter pylori in children with digestive symptoms. METHODS: Prospective and consecutive open trial. The study included patients older than 8 years old with functional dyspepsia, functional

  17. Anestesi Infus Gravimetrik Ketamin dan Propofol pada Anjing (THE GRAVIMETRIC INFUSION ANAESTHESIA WITH KETAMINE AND PROPOFOL IN DOGS

    Directory of Open Access Journals (Sweden)

    I Gusti Ngurah Sudisma

    2014-08-01

    Full Text Available This study aim was to evaluate quality of anaesthesia by using gravimetric infusion anaesthesia withketamine and propofol in dogs. The quality of anaesthesia, duration of actions, and the physiological responsseof anaesthesia were evaluated in twenty domestic dogs. Anaesthesia was induced intramuscularly withatropine (0.03 mg/kg-xylazine (2 mg/kg (AX, intravenously ketamine-propofol (KP (4 mg/kg, andmaintained with continuous intravenous infusion with pre-mixed propofol (P and normal saline containing2 mg/ml of propofol and 2 mg/ml of ketamine (K. Domestic stray dogs were randomly divided into fivegroups. Groups AXKP-K2P2, AXKP-K4P4, and AXKP-K6P6 were treated with ketamine-propofol the dose0.2 mg/kg/minute, 0.4 and 0.6 mg/kg/minute respectively, while group AXKP-P4 was given propofol 0.4 mg/kg/minute and group AXKP-I was given isoflurane 1-2%. Heart rate (HR, respiratory rate (RR,electrocardiogram (ECG, blood oxygen saturation (SpO2, end tidal CO2 (ET CO2, and capillary refill time(CRT were measured. No significant difference (P>0.05 found between the groups in anaesthetion times.All groups showed rapid and smooth inductions, prolonged surgical stage, and rapid recovery. Groups AXKPK2P2and AXKP-K4P4 showed minimal physiological effect on the dogs. The HR, RR, ET CO2, SpO2, CRT,and ECG wave were stabl. Combination of AXKP-K6P6 induced SpO2 depression, increased and instabilityof HR, RR and ET CO2. Groups AXKP-P4 showed decreased of HR and respiratory depression. All anaestheticcombinations showed no significant influence (P>0.05 on the electricity of the dog’s heart. The combinationof ketamine-propofol at dose 0.2 and 0.4 mg/kg/minute were found to be better as an application formaintaining anaesthesia by gravimetric continuous intravenous infusion. The method is a suitablealternative for inhalation anaesthesia in dogs.

  18. Increasing LH pulsatility in women with hypothalamic amenorrhoea using intravenous infusion of Kisspeptin-54.

    Science.gov (United States)

    Jayasena, Channa N; Abbara, Ali; Veldhuis, Johannes D; Comninos, Alexander N; Ratnasabapathy, Risheka; De Silva, Akila; Nijher, Gurjinder M K; Ganiyu-Dada, Zainab; Mehta, Amrish; Todd, Catriona; Ghatei, Mohammad A; Bloom, Stephen R; Dhillo, Waljit S

    2014-06-01

    Hypothalamic amenorrhea (HA) is the one of the most common causes of period loss in women of reproductive age and is associated with deficient LH pulsatility. High-dose kisspeptin-54 acutely stimulates LH secretion in women with HA, but chronic administration causes desensitization. GnRH has paradoxical effects on reproductive activity; we therefore hypothesized that a dose-dependent therapeutic window exists within which kisspeptin treatment restores the GnRH/LH pulsatility in women with HA. The aim of the study was to determine whether constant iv infusion of kisspeptin-54 temporarily increases pulsatile LH secretion in women with HA. Five patients with HA each underwent six assessments of LH pulsatility. Single-blinded continuous iv infusion of vehicle or kisspeptin-54 (0.01, 0.03, 0.10, 0.30, or 1.00 nmol/kg/h) was administered. The LH pulses were detected using blinded deconvolution. Kisspeptin increased LH pulsatility in all patients with HA, with peak responses observed at different doses in each patient. The mean peak number of pulses during infusion of kisspeptin-54 was 3-fold higher when compared with vehicle (number of LH pulses per 8 h: 1.6 ± 0.4, vehicle; 5.0 ± 0.5, kisspeptin-54, P < .01 vs vehicle). The mean peak LH pulse secretory mass during kisspeptin-54 was 6-fold higher when compared with vehicle (LH pulse secretory mass in international units per liter: 3.92 ± 2.31, vehicle; 23.44 ± 12.59, kisspeptin-54; P < .05 vs vehicle). Kisspeptin-54 infusion temporarily increases LH pulsatility in women with HA. Furthermore, we have determined the dose range within which kisspeptin-54 treatment increases basal and pulsatile LH secretion in women with HA. This work provides a basis for studying the potential of kisspeptin-based therapies to treat women with HA.

  19. 75 FR 21641 - Infusion Pumps; Public Meeting; Request for Comments

    Science.gov (United States)

    2010-04-26

    ...] Infusion Pumps; Public Meeting; Request for Comments AGENCY: Food and Drug Administration, HHS. ACTION... announcing a public meeting regarding external infusion pumps. The purpose of the meeting is to inform the public about current problems associated with external infusion pump use, to help the agency identify...

  20. Continuous infusion of chemotherapy: focus on 5-fluorouracil and fluorodeoxyuridine

    NARCIS (Netherlands)

    Poorter, R. L.; Bakker, P. J.; Veenhof, C. H.

    1998-01-01

    Continuous infusion of chemotherapy is one of the developments to try to improve the treatment of metastatic cancer. There is a sound theoretical rationale to deliver cytotoxic drugs as a continuous infusion. Furthermore, the development of reliable venous access devices and portable infusion pumps

  1. An audit of hospital based outpatient infusions and a pilot program of community-based monoclonal antibody infusions.

    LENUS (Irish Health Repository)

    Doran, J-P

    2012-02-01

    INTRODUCTION: Infliximab, a chimeric monoclonal antibody to tumour necrosis factor alpha, is administered as an intravenous infusion requiring a costly hospital day case or inpatient admission. METHODS: An audit of all current therapies given by intravenous infusions in an outpatient setting in St Vincent\\'s University Hospital (SVUH) was undertaken. Furthermore, in conjunction with TCP homecare, we established in a general practise health clinic, the first Irish community infusion centre for the administration of infliximab in August 2006. RESULTS: All outpatient departments indicated that they would favour a centralized hospital infusion unit. There were no adverse events and the mean global satisfaction improved in the community infliximab infusion pilot programme of seven patients. CONCLUSION: This study suggests efficiencies in providing centralized infusion facilities, while the community based infusion of infliximab is feasible and safe in this small cohort and identifies the community infusion unit as a viable and cost efficient alternative for administration of infliximab.

  2. Comparative study between target-controlled-infusion and continuous-infusion anesthesia in dogs treated with methotrimeprazine and treated with propofol and remifentanil Estudo comparativo entre anestesia venosa total alvo-controlada e por infusão contínua em cães pré-tratados com levomepromazina e tratados com propofol e remifentanila

    Directory of Open Access Journals (Sweden)

    Eduardo Hatschbach

    2008-02-01

    Full Text Available PURPOSE: To compare two propofol infusion techniques in bitches subjected to ovaryhisterectomy by estimating the efficiency of the propofol target-dose, evaluating the cardiorespiratory and hemogasimetric attributes, and the bispectral scale index (BIS as well as the recovery period characteristics. METHODS: Twenty anesthetized bitches were divided into two groups of 10 each (G1, G2. Animals of G1 were pre-treated with methotrimeprazine and anesthetized with target-controlled propofol infusion by means of a Harvard infusion pump combined to remifentanil through a syringe pump. RESULTS: Bradycardia and light hypotension, hemogasimetric and respiratory stability besides a good myorelaxation, more evident during continuous infusion and good hypnosis. CONCLUSIONS: Dosis used in both techniques, after methotrimeprazine pre-treatment and combined to the opioid, were efficient for the surgery. The target-controlled anesthesia required a smaller anesthetic consumption (propofol with faster recovery periods.OBJETIVO: Comparar duas técnicas de infusão de propofol em cadelas submetidas à ovariohisterectomia, estudando a eficácia da dose alvo de propofol, avaliando os atributos cardiorrespiratórios, hemogasométricos e escala do índice bispectral, (BIS bem como as características do período de recuperação. MÉTODOS: Foram anestesiadas 20 cadelas, distribuídos em dois grupos (GI e GII. Em GI, os animais foram pré-tratados com levomepromazina e anestesiados com propofol por infusão alvo controlada, através de bomba de infusão Harvard pump, associado com remifentanila, através de bomba de seringa. Em GII, os animais receberam o mesmo tratamento de GI, só que ao invés de receberem o propofol por infusão alvo controlada, receberam o propofol em infusão contínua de velocidade fixa. RESULTADOS: Bradicardia e discreta hipotensão, estabilidade hemogasométrica e respiratória, além de um bom miorrelaxamento, mais evidente na infusão cont

  3. Extended interval between enzyme therapy infusions for adult patients with Gaucher′s disease type 1.

    Directory of Open Access Journals (Sweden)

    Pérez-Calvo J

    2003-01-01

    Full Text Available BACKGROUND: Enzyme replacement therapy (ERT for Gaucher′s disease with alglucerase or imiglucerase is efficacious, well-tolerated and safe. However, cost considerations, visits to medical facilities, potentially duration of theray for life, are issues of major concern to a proportion of treated patients and has, in some cases, led to the withdrawal of therapy. AIMS: To elucidate whether an extension of the interval between enzyme infusions to once every three weeks is as effective in maintaining the clinical responses achieved with the bi-monthly regimen. MATERIALS AND METHODS: Four patients with an optimal response to ERT (at 30 units/kg every two weeks for an average of 27 months, were subjected to enzyme dose/frequency changes that essentially constituted a reduction in cumulative dose over the treatment period. Patients were assessed every 6 months for alterations in haematological parameters, plasma chitotriosidase levels, liver and spleen size, and bone symptoms. RESULTS: All patients had to resume the previous infusion schedule of once every two weeks; one because of new bone marrow infiltrates, two because of visceral enlargement, and the fourth due to progressive anaemia. CONCLUSIONS: This limited experience suggests that a reduction in enzyme dose associated with an extended interval between infusions may lead to variable disease control, and underscores the need for individualization of enzyme therapy.

  4. Association with polymorphic marmoset cytochrome P450 2C19 of in vivo hepatic clearances of chirally separated R-omeprazole and S-warfarin using individual marmoset physiologically based pharmacokinetic models.

    Science.gov (United States)

    Kusama, Takashi; Toda, Akiko; Shimizu, Makiko; Uehara, Shotaro; Inoue, Takashi; Uno, Yasuhiro; Utoh, Masahiro; Sasaki, Erika; Yamazaki, Hiroshi

    2017-11-10

    1. Simulated clearances of R-warfarin and efavirenz were recently reported for individual cynomolgus monkeys genotyped for cytochrome P450 2C19 and 2C9, respectively. To expand and verify this modeling procedure, simulations of R/S-omeprazole and R/S-warfarin clearances after oral administrations in individual marmosets were performed using individual simplified physiologically based pharmacokinetic (PBPK) modeling consisting of gut, liver and central compartments. 2. Pharmacokinetics of R/S-omeprazole were chirally determined using the previously reported plasma microsamples in this study. The areas under the plasma concentration/time curves (AUC) of R-omeprazole and S-warfarin, but not S-omeprazole and R-warfarin, after oral administrations in the P450 2C19 homozygous mutant group were significantly higher than those in the wild-type group. These modeled hepatic intrinsic clearances were also significantly associated with the marmoset P450 2C19 genotypes. Other parameter values, e.g. absorption rate constants or systemic circulation volumes, were not likely determining factors. 3. The reported individual AUC values measured in 4-6 marmosets after oral R-omeprazole and S-warfarin administrations were significantly correlated with the AUC values predicted using the PBPK models after virtual administrations. 4. This study indicates that clearances of R-omeprazole, S-warfarin and related medicines associated with polymorphic P450 2C19 in individual marmosets can be simulated using simplified individual PBPK models.

  5. Comparative study of novel spectrophotometric methods manipulating ratio spectra: An application on pharmaceutical ternary mixture of omeprazole, tinidazole and clarithromycin

    Science.gov (United States)

    Lotfy, Hayam Mahmoud; Abdel-Monem Hagazy, Maha

    2012-10-01

    Three simple, specific, accurate and precise spectrophotometric methods manipulating ratio spectra are developed for simultaneous determination of omeprazole (OM), tinidazole (TN) and clarithromycin (CL) in tablets. Method A, is an extended ratio subtraction one (EXRSM). Method B is a ratio difference spectrophotometric one (RDSM), while method C is mean centering of ratio spectra (MCR). The calibration curves are linear over the concentration range of 1-20 μg/mL, 10-60 μg/mL and 0.25-1.0 mg/mL for OM, TN and CL, respectively. The specificity of the developed methods is investigated by analyzing laboratory prepared mixtures of the three drugs and their combined dosage form. Standard deviation values are less than 1.5 in the assay of raw materials and tablets. The three methods are validated as per ICH guidelines and accuracy, precision, repeatability and robustness are found to be within the acceptable limits.

  6. Retrospective Review of Hydrochloric Acid Infusion for the Treatment of Metabolic Alkalosis in Surgical Intensive Care Unit Patients.

    Science.gov (United States)

    Guffey, Jason D; Haas, Curtis E; Crowley, Amber; Connor, Kathryn A; Kaufman, David C

    2018-01-01

    Older reports of use of hydrochloric acid (HCl) infusions for treatment of metabolic alkalosis document variable dosing strategies and risk. This study sought to characterize use of HCl infusions in surgical intensive care unit patients for the treatment of metabolic alkalosis. This retrospective review included patients who received a HCl infusion for >8 hours. The primary end point was to evaluate the utility of common acid-base equations for predicting HCl dose requirements. Secondary end points evaluated adverse effects, efficacy, duration of therapy, and total HCl dose needed to correct metabolic alkalosis. Data on demographics, potential causes of metabolic alkalosis, fluid volume, and duration of diuretics as well as laboratory data were collected. A total of 30 patients were included, and the average HCl infusion rate was 10.5 ± 3.7 mEq/h for an average of 29 ± 14.6 hours. Metabolic alkalosis was primarily diuretic-induced (n = 26). Efficacy was characterized by reduction in the median total serum CO 2 from 34 to 27 mM/L ( P metabolic alkalosis, and no serious adverse events were seen. In this clinical setting, the baseline chloride ion deficit and SIDa were not useful for prediction of total HCl dose requirement, and serial monitoring of response is recommended.

  7. Anaphylaxis after intravenous infusion of dexketoprofen trometamol

    Directory of Open Access Journals (Sweden)

    Sertac Guler

    2016-09-01

    Full Text Available Dexketoprofen trometamol (DT, a nonsteroidal anti-inflammatory drug, is a highly water-soluble salt and active enantiomer of rac-ketoprofen. Its parenteral form is commonly used for acute pain management in emergency departments of our country. Side effects such as diarrhea, indigestion, nausea, stomach pain, and vomiting may be seen after the use of DT. Anaphylactic shock (AS secondary to infusion of DT is very rare and, to our knowledge, it is the first case report describing this side effect. This case report was presented to emphasize that AS may be seen after the use of DT. Keywords: Anaphylactic shock, Dexketoprofen trometamol, Intravenous infusion (MeSH database