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Sample records for mg oral dose

  1. Effects of a single, oral 60 mg caffeine dose on attention in healthy adult subjects.

    Science.gov (United States)

    Wilhelmus, Micha Mm; Hay, Justin L; Zuiker, Rob Gja; Okkerse, Pieter; Perdrieu, Christelle; Sauser, Julien; Beaumont, Maurice; Schmitt, Jeroen; van Gerven, Joop Ma; Silber, Beata Y

    2017-02-01

    Caffeine induces positive effects on sustained attention, although studies assessing the acute effects of low caffeine dose (caffeine on sustained attention in tests lasting up to 45 minutes using 82 low or non-caffeine-consuming healthy male ( n=41) and female ( n=41) adults aged between 40 and 60 years. Vigilance was measured using Mackworth Clock test, Rapid Visual Information Processing Test, adaptive tracking test, saccadic eye movement and attention switch test. Effects on mood and fatigue were analysed using Bond and Lader and Caffeine Research visual analogue scales, and Samn-Perelli questionnaire. Saliva sampling was performed for both compliance and caffeine pharmacokinetic analysis. Administration of a 60 mg caffeine dose resulted in a significant improvement in sustained attention compared with the placebo. Also a significantly improved peak saccadic velocity and reaction time performance was found, and decreased error rate. Significantly increased feelings of alertness, contentment and overall mood after caffeine treatment compared with placebo were observed. This study demonstrated that in healthy adult subjects oral administration of a single 60 mg caffeine dose elicited a clear enhancement of sustained attention and alertness, measured both in multiple objective performances and in subjective scales.

  2. Bioequivalence of a single 400-mg dose of imatinib 100-mg oral tablets and a 400-mg tablet in healthy adult Korean volunteers.

    Science.gov (United States)

    Lee, Hae Won; Seong, Sook Jin; Park, Sung Min; Lee, Joomi; Gwon, Mi-Ri; Kim, Hyun-Ju; Lim, Sung Mook; Lim, Mi-Sun; Kim, Woomi; Yang, Dong Heon; Yoon, Young-Ran

    2015-06-01

    Imatinib mesylate (IM) is a selective tyrosine kinase inhibitor for the treatment of chronic myeloid leukemia and gastrointestinal stromal tumors. A new once-daily 400-mg film-coated tablet of imatinib has been developed by a pharmaceutical company in Korea. The present study was designed to assess and compare the PK parameters, bioavailability, and bioequivalence of the new imatinib 400-mg formulation (test) versus the conventional 100-mg formulation (reference) administered as a single 400-mg dose in healthy adult male volunteers. This randomized, open-label, single-dose, two-way crossover study was conducted in healthy Korean male volunteers. Eligible subjects were randomly assigned in a 1 : 1 ratio to receive 400 mg of the test (one 400-mg tablet) or reference (four 100-mg tablets) formulation, followed by a 2-week washout period and administration of the alternate formulation. Serial blood samples were collected at 0 (predose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 48, and 72 hours after administration. Plasma imatinib concentrations were determined using liquid chromatography coupled with tandem mass spectrometry. The formulations were to be considered bioequivalent if the 90% confidence intervals (CIs) of the adjusted geometric mean ratios for Cmax, AUC(0-t), and AUC(0-∞)ž were within the predetermined range of 0.80 - 1.25. In total, 35 subjects completed the study. No serious adverse event was reported during the study. The 90% CIs of the adjusted geometric mean ratios of the test formulation to the reference formulation for C(max), AUC(0-t) and AUC(0-∞)ž of imatinib were all within the bioequivalence criteria range of 0.8 - 1.25. The test formulation of imatinib met the Korean regulatory requirements for bioequivalence. Both imatinib formulations were well-tolerated in all subjects.

  3. Efficacy and safety of a single oral 150 mg dose of fluconazole for the treatment of vulvovaginal candidiasis in Japan.

    Science.gov (United States)

    Mikamo, Hiroshige; Matsumizu, Miyako; Nakazuru, Yoshiomi; Okayama, Akifumi; Nagashima, Masahito

    2015-07-01

    Vulvovaginal candidiasis is the second most common cause of vaginal infections following bacterial vaginosis. For the treatment of vulvovaginal candidiasis, antifungal agents are used either as topical (vaginal tablets and cream) or oral formulations. A single oral 150 mg dose of fluconazole has been recommended as the standard therapy for uncomplicated, acute vulvovaginal candidiasis in global guidelines; however, in Japan oral fluconazole therapy has not been approved. We conducted a phase 3 study to evaluate the efficacy and safety of a single oral 150 mg dose of fluconazole in Japanese subjects with vulvovaginal candidiasis for regulatory submission. A total of 157 subjects received a single oral 150 mg dose of fluconazole. Candida species (104 strains) were identified by fungal culture from 102 subjects at baseline, including Candida albicans (100 strains). The efficacy rate for the therapeutic outcome (assessed based on a comprehensive evaluation of the clinical and mycological efficacy in each subject) was 74.7% (74/99) on Day 28 in the modified Intent-To-Treat (m-ITT) population. Concerning the clinical and mycological efficacy on Day 28 in the m-ITT population, the cure, cure or improvement, and eradication rates were 81.6%, 95.9%, and 85.9%, respectively. The most common treatment-related adverse events were diarrhea and nausea (1.9% for each). No clinically significant safety issues were reported. A single oral 150 mg dose of fluconazole demonstrated excellent therapeutic efficacy and was well tolerated in Japanese subjects with vulvovaginal candidiasis. NCT01806623. Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  4. Tramadol hydrochloride 75 mg/dexketoprofen 25 mg oral fixed-dose combination in moderate-to-severe acute pain: sustained analgesic effect over a 56-h period in the postoperative setting.

    Science.gov (United States)

    Montero Matamala, A; Bertolotti, M; Contini, M P; Guerrero Bayón, C; Nizzardo, A; Paredes Lario, I; Pizà Vallespir, B; Scartoni, S; Tonini, G; Capriati, A; Pellacani, A

    2017-06-01

    Multimodal analgesia constitutes a common strategy in pain management. A tramadol hydrochloride 75 mg/dexketoprofen 25 mg oral fixed combination (TRAM/DKP 75 mg/25 mg) has been recently registered and released in Europe for the treatment of moderate-to-severe acute pain. This paper provides additional analyses on the results of two phase III clinical trials (DEX-TRA-04 and DEX-TRA-05) on postoperative pain to document its sustained effect. The analysis was applied to a modified intention-to-treat population (mITT, n = 933) of patients undergoing active treatment from the first dose, to assess the sustained effect of TRAM/DKP 75 mg/25 mg on pain intensity (PI-VAS 0-100) over 56 h from first drug intake. The superior analgesic effect of TRAM/DKP 75 mg/25 mg over 56 h in terms of difference in PI-VAS (mean [SE]) was shown for DEX-TRA-04 (-11.0 [0.55] over dexketoprofen 25 mg and -9.1 [0.55] over tramadol 100 mg, P ≤ 0.0001) and for DEX-TRA-05 (-10.4 [0.51] over dexketoprofen 25 mg and -8.3 [0.51] over tramadol 100 mg, P ≤ 0.0001). The statistical analysis performed on data coming from both studies confirms the superior sustained analgesia of TRAM/DKP 75 mg/25 mg over tramadol 100 mg and dexketoprofen 25 mg. These results are consistent with the previously published data obtained on the ITT population and strongly support the role of this oral fixed-dose combination in the treatment of moderate-to-severe acute pain. Copyright 2017 Clarivate Analytics.

  5. Concentrations of garenoxacin in plasma, bronchial mucosa, alveolar macrophages and epithelial lining fluid following a single oral 600 mg dose in healthy adult subjects.

    Science.gov (United States)

    Andrews, J; Honeybourne, D; Jevons, G; Boyce, M; Wise, R; Bello, A; Gajjar, D

    2003-03-01

    A microbiological assay was used to measure concentrations of garenoxacin (BMS-284756) in plasma, bronchial mucosa (BM), alveolar macrophages (AM) and epithelial lining fluid (ELF), following a single 600 mg oral dose. Twenty-four healthy subjects were allocated into four nominal time intervals after the dose, 2.5-3.5, 4.5-5.5, 10.5-11.5 and 23.5-24.5 h. Mean concentrations in plasma, BM, AM and ELF, respectively, for the four nominal time windows were for 2.5-3.5 h 10.0 mg/L (S.D. 2.8), 7.0 mg/kg (S.D. 1.3), 106.1 mg/L (S.D. 60.3) and 9.2 mg/L (S.D. 3.6); 4.5-5.5 h 8.7 mg/L (S.D. 2.2), 6.0 mg/kg (S.D. 1.9), 158.6 mg/L (S.D. 137.4) and 14.3 mg/L (S.D. 8.2); 10.5-11.5 h 6.1 mg/L (S.D. 1.9), 4.0 mg/kg (S.D. 1.4), 76.0 mg/L (S.D. 47.7) and 7.9 mg/L (S.D. 4.6); and 23.5-24.5 h 2.1 mg/L (S.D. 0.5), 1.7 mg/kg (S.D. 0.7), 30.7 mg/L (S.D. 12.9) and 3.3 mg/L (S.D. 2.3). Concentrations at all sites exceeded MIC(90)s for the common respiratory pathogens Haemophilus influenzae (0.03 mg/L), Moraxella catarrhalis (0.015 mg/L) and Streptococcus pneumoniae (0.06 mg/L). These data suggest that garenoxacin should be effective in the treatment of community-acquired pneumonia and chronic obstructive pulmonary disease.

  6. Fixed-Dose Combination Gel of Adapalene and Benzoyl Peroxide plus Doxycycline 100 mg versus Oral Isotretinoin for the Treatment of Severe Acne: Efficacy and Cost Analysis.

    Science.gov (United States)

    Penna, Pete; Meckfessel, Matthew H; Preston, Norman

    2014-01-01

    Acne vulgaris is a chronic skin disease with a high prevalence. Left untreated or inadequately treated, acne vulgaris can lead to psychological and physical scarring, as well as to unnecessary medical expenses. Oral isotretinoin is an effective treatment for severe resistant nodular and conglobate acne vulgaris. A regimen consisting of a fixed-dose combination of adapalene and benzoyl peroxide gel, 0.1%/2.5% (A-BPO) with oral doxycycline 100 mg (A-BPO/D) has been demonstrated to be efficacious and well tolerated in patients with severe acne and may be an alternative to oral isotretinoin for some patients with severe acne. The objective of this analysis was to compare the relative efficacy and associated costs of A-BPO/D versus oral isotretinoin. In this analysis, comparisons of relative efficacy were made using previously published studies involving similar patient populations with severe acne that warrant the use of oral isotretinoin. The pricing for oral doxycycline and oral isotretinoin was estimated based on the maximum allowable cost from 9 states, and the pricing for A-BPO was calculated as the range between the average wholesale price and the wholesale acquisition cost. For this analysis, 2 treatment models were generated to compare costs: (1) a basic treatment model that examined the costs of an initial regimen of either A-BPO/D or oral isotretinoin without considering probable outcomes, and (2) a long-term model that factored in likely treatment outcomes and subsequent treatments into associated costs. The basic treatment model assumed that patients would be prescribed a single regimen of A-BPO/D for 12 weeks or oral isotretinoin for 20 weeks. The long-term model considered the probability of each treatment successfully managing patients' acne, as well as likely additional regimens of A-BPO monotherapy or an additional regimen of oral isotretinoin. As a result of different treatment durations, the costs for each treatment were normalized to weekly cost of

  7. Average bioequivalence of single 500 mg doses of two oral formulations of levofloxacin: a randomized, open-label, two-period crossover study in healthy adult Brazilian volunteers

    Directory of Open Access Journals (Sweden)

    Eunice Kazue Kano

    2015-03-01

    Full Text Available Average bioequivalence of two 500 mg levofloxacin formulations available in Brazil, Tavanic(c (Sanofi-Aventis Farmacêutica Ltda, Brazil, reference product and Levaquin(c (Janssen-Cilag Farmacêutica Ltda, Brazil, test product was evaluated by means of a randomized, open-label, 2-way crossover study performed in 26 healthy Brazilian volunteers under fasting conditions. A single dose of 500 mg levofloxacin tablets was orally administered, and blood samples were collected over a period of 48 hours. Levofloxacin plasmatic concentrations were determined using a validated HPLC method. Pharmacokinetic parameters Cmax, Tmax, Kel, T1/2el, AUC0-t and AUC0-inf were calculated using noncompartmental analysis. Bioequivalence was determined by calculating 90% confidence intervals (90% CI for the ratio of Cmax, AUC0-t and AUC0-inf values for test and reference products, using logarithmic transformed data. Tolerability was assessed by monitoring vital signs and laboratory analysis results, by subject interviews and by spontaneous report of adverse events. 90% CIs for Cmax, AUC0-t and AUC0-inf were 92.1% - 108.2%, 90.7% - 98.0%, and 94.8% - 100.0%, respectively. Observed adverse events were nausea and headache. It was concluded that Tavanic(c and Levaquin(c are bioequivalent, since 90% CIs are within the 80% - 125% interval proposed by regulatory agencies.

  8. Safety and pharmacokinetics of single and multiple intravenous bolus doses of diclofenac sodium compared with oral diclofenac potassium 50 mg: A randomized, parallel-group, single-center study in healthy subjects.

    Science.gov (United States)

    Munjal, Sagar; Gautam, Anirudh; Okumu, Franklin; McDowell, James; Allenby, Kent

    2016-01-01

    In a randomized, parallel-group, single-center study in 42 healthy adults, the safety and pharmacokinetic parameters of an intravenous formulation of 18.75 and 37.5 mg diclofenac sodium (DFP-08) following single- and multiple-dose bolus administration were compared with diclofenac potassium 50 mg oral tablets. Mean AUC0-inf values for a 50-mg oral tablet and an 18.75-mg intravenous formulation were similar (1308.9 [393.0]) vs 1232.4 [147.6]). As measured by the AUC, DFP-08 18.75 mg and 37.5 mg demonstrated dose proportionality for extent of exposure. One subject in each of the placebo and DFP-08 18.75-mg groups and 2 subjects in the DFP-08 37.5-mg group reported adverse events that were considered by the investigator to be related to the study drug. All were mild in intensity and did not require treatment. Two subjects in the placebo group and 1 subject in the DFP-08 18.75-mg group reported grade 1 thrombophlebitis; no subjects reported higher than grade 1 thrombophlebitis after receiving a single intravenous dose. The 18.75- and 37.5-mg doses of intravenous diclofenac (single and multiple) were well tolerated for 7 days. Additional efficacy and safety studies are required to fully characterize the product. © 2015, The American College of Clinical Pharmacology.

  9. Bioequivalence of 250 mg lysine clonixinate tablets after a single oral dose in a healthy female Mexican population under fasting conditions.

    Science.gov (United States)

    Marcelín-Jiménez, G; Angeles, A C P; García, A; Morales, M; Rivera, L; Martín-Del-Campo, A

    2010-05-01

    To evaluate the bioequivalence between two 250 mg-tablets of lysine clonixinate, Dorixina Forte (Siegfried Rhein, México) as reference product, and Prestodol (Farmaceúticos Rayere, S.A., México) as test formulation. 26 healthy adult female Mexican volunteers received a single oral dose of 250-mg lysine clonixinate under fasting conditions. The drug was administered following a randomized, two-period, two-sequence, cross-over design. Twelve serial blood samples were collected up to 8 h after dosing, and clonixin (CLX) was measured by ultra-performance liquid chromatography (UPLC) coupled with tandem mass spectrometry. Decimal logarithm values of Cmax and area under the curve (AUC) were used to construct a classic confidence interval at 90% (90% CI). Bioequivalence was established if 90% CI of mean ratios (test/reference) fall within the 0.8-1.25 range. Volunteers formed a homogeneous population in terms of age (27.2 +/- 6.3 years), weight (55.9 +/- 6.5 kg), height (1.6 +/- 0.04 m), and body mass index (BMI) (22.91 +/- 2.03 kg/m(2)). Reference formulation exhibited the following pharmacokinetics: C(max) (32.39 +/- 8.32 microg/ml); t(max) (0.64 +/- 0.2 h); AUC0-8h (48.92 +/- 16.51 microg x h/ml); t1/2 (1.3 +/- 0.24 h); CLapp (5.64 +/- 1.99 l/h), and Vdapp (10.22 +/- 2.9 l). Concerning bioequivalence, 90% CI were: C(max) (82.32 - 98.79), AUC0-t (94.59-106.29), and AUC(0-inf) (94.61-106.42), with a statistical power of > 0.90 at every tested interval. This single-dose study found that both 250-mg immediate-release tablets of lysine clonixinate met the Mexican regulatory criteria for bioequivalence in these volunteers.

  10. Concentrations of moxifloxacin in serum and pulmonary compartments following a single 400 mg oral dose in patients undergoing fibre-optic bronchoscopy.

    Science.gov (United States)

    Soman, A; Honeybourne, D; Andrews, J; Jevons, G; Wise, R

    1999-12-01

    The concentrations of moxifloxacin achieved after a single 400 mg dose were measured in serum, epithelial lining fluid (ELF), alveolar macrophages (AM) and bronchial mucosa (BM). Concentrations were determined using a microbiological assay. Nineteen patients undergoing fibre-optic bronchoscopy were studied. Mean serum, ELF, AM and BM concentrations at 2.2, 12 and 24 h were as follows: 2.2 h: 3.2 mg/L, 20.7 mg/L, 56.7 mg/L, 5.4 mg/kg; 12 h: 1.1 mg/L, 5.9 mg/L, 54.1 mg/L, 2.0 mg/kg; 24 h: 0.5 mg/L, 3.6 mg/L, 35.9 mg/L, 1.1 mg/kg, respectively. These concentrations exceed the MIC(90)s for common respiratory pathogens such as Streptococcus pneumoniae (0.25 mg/L), Haemophilus influenzae (0.03 mg/L), Moraxella catarrhalis (0.12 mg/L), Chlamydia pneumoniae (0.12 mg/L) and Mycoplasma pneumoniae (0. 12 mg/L) and indicate that moxifloxacin should be effective in the treatment of community-acquired, lower respiratory tract infections.

  11. 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

  12. Relative bioavailability of generic and branded 250-mg and 500-mg oral chlorphenesin carbamate tablets in healthy Korean volunteers: a single-dose, randomized-sequence, open-label, two-period crossover trial.

    Science.gov (United States)

    Yu, Ji-young; Song, Hyun Ho; Kim, Bo Gyeom; Park, Hyeon Ju; Choi, Kwang Sik; Kwon, Young Ee

    2009-11-01

    Chlorphenesin carbamate is a skeletal muscle relaxant approved in Korea for use in the treatment of pain and discomfort related to skeletal muscle trauma and inflammation. The aim of this study was to assess the bioequivalence of a generic formulation of chlorphenesin carbamate at doses of 250 and 500 mg and 2 branded formulations of the same doses in healthy Korean adults. This single-dose, randomized-sequence, open-label, 2-period crossover study was conducted in healthy Korean male and female volunteers. Subjects were assigned to receive, in a randomized sequence, a single dose of the generic (test) and branded (reference) formulations of chlorphenesin carbamate at a dose of 250 or 500 mg. Blood samples were drawn at 0, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 9, 12, and 15 hours after administration. Pharmacokinetic properties (C(max), T(max), AUC(0-t) AUC(0-infinity), t(1/2), and ke) were determined using HPLC. The formulations were to be considered bioequivalent if the 90% CIs of the treatment ratios of the geometric means of C(max) and AUC(0-t) were within a predetermined range of log 0.80 to log 1.25 based on regulatory criteria. Tolerability was assessed by monitoring for adverse events (AEs) on physical examination and/or e-mail and personal interview at the beginning and end of each study period. Twenty-eight subjects (22 men, 6 women) received chlorphenesin carbamate at the 250-mg dose, and 24 male subjects received the 500-mg dose. The mean (SD) ages of the subjects were 24.0 (2.6) and 24.0 (1.9) years in the 250- and 500-mg groups, respectively. No significant differences were found between the test and reference formulations (90% CIs: C(max), 1.0048-1.1153 with the 250-mg dose and 0.9630-1.1189 with the 500-mg dose; AUC(0-t), 0.9882-1.0546 and 0.9842-1.0578, respectively). No clinically significant AEs (upper gastric pain, abdominal bloating, pyrexia, edema, nausea, heartburn, constipation, headache, dizziness, drowsiness, or fatigue) were reported throughout

  13. Lung concentrations of telithromycin after oral dosing.

    Science.gov (United States)

    Khair, O A; Andrews, J M; Honeybourne, D; Jevons, G; Vacheron, F; Wise, R

    2001-06-01

    Concentrations of telithromycin were measured in plasma, bronchial mucosa (BM), epithelial lining fluid (ELF) and alveolar macrophages (AM) following multiple oral doses. Concentrations were determined using a microbiological assay. There were 20 subjects in the study, allocated to three nominal time periods: 2, 12 and 24 h. Mean concentrations in plasma, BM, ELF and AM for 2, 12 and 24 h were as follows: 2 h, 1.86 mg/L, 3.88 mg/kg, 14.89 mg/L and 69.32 mg/L; 12 h, 0.23 mg/L, 1.41 mg/kg, 3.27 mg/L and 318.1 mg/L; and 24 h, 0.08 mg/L, 0.78 mg/kg, 0.97 mg/L and 161.57 mg/L. These concentrations of telithromycin in BM and ELF exceeded for 24 h the mean MIC90s of the common respiratory pathogens Streptococcus pneumoniae (0.12 mg/L) and Moraxella catarrhalis (0.03 mg/L), as well as the atypical microorganism Mycoplasma pneumoniae (0.001 mg/L), and suggest that telithromycin may be effective for the treatment of community-acquired pneumonia and chronic obstructive pulmonary disease.

  14. The concentrations of clinafloxacin in alveolar macrophages, epithelial lining fluid, bronchial mucosa and serum after administration of single 200 mg oral doses to patients undergoing fibre-optic bronchoscopy.

    Science.gov (United States)

    Honeybourne, D; Andrews, J M; Cunningham, B; Jevons, G; Wise, R

    1999-01-01

    The concentrations of clinafloxacin were measured in serum, bronchial mucosa, alveolar macrophages and epithelial lining fluid after single 200 mg oral doses of clinafloxacin had been administered to 15 subjects who were undergoing bronchoscopy. Concentrations were measured using a microbiological assay method. Mean concentrations in serum, bronchial mucosa, alveolar macrophages and epithelial lining fluid at a mean of 1.27 h post-dose were 1.54, 2.65, 15.60 and 2.71 mg/L respectively. These site concentrations exceeded the MIC90 for common respiratory pathogens and indicate that clinafloxacin is likely to be effective in the treatment of a wide range of respiratory tract infections.

  15. Relative bioavailability of two oral formulations of risperidone 2 mg: A single-dose, randomized-sequence, open-label, two-period crossover comparison in healthy Brazilian volunteers.

    Science.gov (United States)

    Belotto, Karisa Cristina Rodrigues; Raposo, Nádia Rezende Barbosa; Ferreira, Aline Siqueira; Gattaz, Wagner Farid

    2010-11-01

    Risperidone (RSP) is a benzisoxazole antipsychotic agent used to treat schizophrenia and other psychiatric illnesses in adults and children (including those with autism). After oral administration, RSP is completely absorbed from the gastrointestinal tract and undergoes hydroxylation to yield 9-hydroxyrisperidone (9-OH-RSP), an active metabolite that has a pharmacologic profile and potency similar to RSP. The aims of this study were to compare the relative bioavailability of a pharmaceutical-equivalent (test) formulation with a reference formulation of oral RSP 2 mg, both available commercially on the Brazilian pharmaceutical market, and to generate data regarding the oral bioavailability of the tested drug in healthy Brazilian volunteers. This single-dose, randomized-sequence, open-label, 2-period crossover study was conducted in healthy Brazilian volunteers from August to December 2008. Subjects were randomly assigned to receive the test formulation followed by the reference formulation or vice versa, with a 30-day washout period between doses. Study drugs were administered after a 12-hour overnight fast. For pharmacokinetic analysis, blood samples were drawn at 0 (baseline), 0.25, 0.5, 1, 1.5, 3, 5, 8, 12, 24, 48, 72, 96, and 120 hours after administration. Plasma concentrations of RSP and 9-OH-RSP were determined using LC-MS/MS. The test and reference formulations were to be considered bioequivalent if the 90% CIs for the geometric mean test/reference ratios were within a predetermined range of 80% to 125%, in accordance with the policies of the Brazilian Sanitary Surveillance Agency and the US Food and Drug Administration. Tolerability was determined using clinical assessments, monitoring of vital signs, analysis of laboratory test results, and subject interviews regarding adverse events. A total of 22 subjects were enrolled (11 men, 11 women; mean [SD] age, 32 [12] years [range, 1858 years]; weight, 70.4 [11.9] kg [range, 50-103 kg]; height, 1.67 [0.08] m

  16. Split high-dose oral levothyroxine treatment as a successful therapy option in myxedema coma.

    Science.gov (United States)

    Charoensri, Suranut; Sriphrapradang, Chutintorn; Nimitphong, Hataikarn

    2017-10-01

    High-dose intravenous thyroxine (T4) is the preferable treatment for myxedema coma. We describe the clinical course of a 69-year-old man who presented with myxedema coma and received oral levothyroxine (LT4) therapy (1 mg) in a split dose. This suggests split high-dose oral LT4 as a therapeutic option in myxedema coma.

  17. Oral desensitization to milk: how to choose the starting dose!

    Science.gov (United States)

    Mori, Francesca; Pucci, Neri; Rossi, Maria Elisabetta; de Martino, Maurizio; Azzari, Chiara; Novembre, Elio

    2010-01-01

    Mori F, Pucci N, Rossi ME, de Martino M, Azzari C, Novembre E. Oral desensitization to milk: how to choose the starting dose! Pediatr Allergy Immunol 2010: 21: e450–e453. © 2009 John Wiley & Sons A/S A renewed interest in oral desensitization as treatment for food allergy has been observed in the last few years. We studied a novel method based on the end point skin prick test procedure to establish the starting dose for oral desensitization in a group of 30 children higly allergic to milk. The results (in terms of reactions to the first dose administered) were compared with a group of 20 children allergic to milk as well. Such control group started to swallow the same dose of 0.015 mg/ml of milk. None reacted to the first dose when administered according to the end point skin prick test. On the other side, ten out of 20 children (50%) from the control group showed mild allergic reactions to the first dose of milk. In conclusion the end point skin prick test procedure results safe and easy to be performed in each single child in order to find out the starting dose for oral desensitization to milk, also by taking into account the individual variability. PMID:19624618

  18. The effects of intranasal esketamine (84 mg) and oral mirtazapine (30 mg) on on-road driving performance : a double-blind, placebo-controlled study

    NARCIS (Netherlands)

    van de Loo, Aurora J A E; Bervoets, Adriana C; Mooren, Loes; Bouwmeester, Noor H; Garssen, Johan; Zuiker, Rob; van Amerongen, Guido; van Gerven, Joop; Singh, Jaskaran; der Ark, Peter Van; Fedgchin, Maggie; Morrison, Randall; Wajs, Ewa; Verster, Joris

    2017-01-01

    RATIONALE: The purpose of this study is to evaluate the single dose effect of intranasal esketamine (84 mg) compared to placebo on on-road driving performance. Mirtazapine (oral, 30 mg) was used as a positive control, as this antidepressant drug is known to negatively affect driving performance.

  19. Pharmacokinetics of Escalating Doses of Oral Psilocybin in Healthy Adults.

    Science.gov (United States)

    Brown, Randall T; Nicholas, Christopher R; Cozzi, Nicholas V; Gassman, Michele C; Cooper, Karen M; Muller, Daniel; Thomas, Chantelle D; Hetzel, Scott J; Henriquez, Kelsey M; Ribaudo, Alexandra S; Hutson, Paul R

    2017-12-01

    Psilocybin is a psychedelic tryptamine that has shown promise in recent clinical trials for the treatment of depression and substance use disorders. This open-label study of the pharmacokinetics of psilocybin was performed to describe the pharmacokinetics and safety profile of psilocybin in sequential, escalating oral doses of 0.3, 0.45, and 0.6 mg/kg in 12 healthy adults. Eligible healthy adults received 6-8 h of preparatory counseling in anticipation of the first dose of psilocybin. The escalating oral psilocybin doses were administered at approximately monthly intervals in a controlled setting and subjects were monitored for 24 h. Blood and urine samples were collected over 24 h and assayed by a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for psilocybin and psilocin, the active metabolite. The pharmacokinetics of psilocin were determined using both compartmental (NONMEM) and noncompartmental (WinNonlin) methods. No psilocybin was found in plasma or urine, and renal clearance of intact psilocin accounted for less than 2% of the total clearance. The pharmacokinetics of psilocin were linear within the twofold range of doses, and the elimination half-life of psilocin was 3 h (standard deviation 1.1). An extended elimination phase in some subjects suggests hydrolysis of the psilocin glucuronide metabolite. Variation in psilocin clearance was not predicted by body weight, and no serious adverse events occurred in the subjects studied. The small amount of psilocin renally excreted suggests that no dose reduction is needed for subjects with mild-moderate renal impairment. Simulation of fixed doses using the pharmacokinetic parameters suggest that an oral dose of 25 mg should approximate the drug exposure of a 0.3 mg/kg oral dose of psilocybin. Although doses of 0.6 mg/kg are in excess of likely therapeutic doses, no serious physical or psychological events occurred during or within 30 days of any dose. NCT02163707.

  20. SODIUM BICARBONATE FACILITATES LOW-DOSE ORAL TOLERANCE TO PEANUT IN MICE

    Science.gov (United States)

    Rationale: Oral tolerance specifically inhibits production of allergic IgE antibody and is therefore a potential method for suppressing food allergy. We have previously demonstrated that a single oral dose of one mg is sufficient to induce oral tolerance to egg white but not pean...

  1. Single dose oral flurbiprofen for acute postoperative pain in adults

    Science.gov (United States)

    Sultan, Asquad; McQuay, Henry J; Moore, R Andrew; Derry, Sheena

    2014-01-01

    Background Flurbiprofen is a non-selective non-steroidal anti-inflammatory drug (NSAID), related to ibuprofen and naproxen, used to treat acute and chronic painful conditions. There is no systematic review of its use in acute postoperative pain. Objectives To assess efficacy, duration of action, and associated adverse events of single dose oral flurbiprofen in acute postoperative pain in adults. Search methods We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies to January 2009. Selection criteria Randomised, double blind, placebo-controlled trials of single dose orally administered flurbiprofen in adults with moderate to severe acute postoperative pain. Data collection and analysis Two review authors independently assessed trial quality and extracted data. Pain relief or pain intensity data were extracted and converted into the dichotomous outcome of number of participants with at least 50% pain relief over 4 to 6 hours, from which relative risk (RR) and number needed to treat to benefit (NNT) were calculated. Numbers of participants using rescue medication over specified time periods, and time to use of rescue medication, were sought as additional measures of efficacy. Information on adverse events and withdrawals were collected. Main results Eleven studies compared flurbiprofen (699 participants) with placebo (362 participants) in studies lasting 6 to 12 hours. Studies were of adequate reporting quality, and most participants had pain following dental extractions. The dose of flurbiprofen used was 25 mg to 100 mg, with most information for 50 mg and 100 mg. The NNT for at least 50% pain relief over 4 to 6 hours for flurbiprofen 50 mg compared with placebo (692 participants) was 2.7 (2.3 to 3.3) and for 100 mg (416 participants) it was 2.5 (2.0 to 3.1). With flurbiprofen 50 mg and 100 mg 65% to 70% of participants experienced at least 50% pain relief, compared with 25% to 30% with placebo. Rescue medication was used by 25

  2. Bioequivalence of 2 Formulations of Sildenafil Oral Soluble Film 100 mg and Sildenafil Citrate (Viagra) 100 mg Oral Tablets in Healthy Male Volunteers.

    Science.gov (United States)

    Dadey, Eric

    Sildenafil citrate tablets (VIAGRA; Pfizer Inc) have been used since 1998 as an oral therapy for the treatment of erectile dysfunction. However, in some cases, patients may have difficulty in swallowing tablets, and the need to use water to aid in the oral administration of the tablets has the potential to interrupt the sexual encounter, reduce spontaneity, and therefore decrease the quality of the experience. Two oral soluble film (OSF) formulations of sildenafil were developed using MonoSol Rx's proprietary PharmFilm technology. Both films were formulated to dissolve rapidly on the tongue, thereby releasing the drug into the oral cavity, whereupon it is swallowed without the use of water. From a patient perspective, it is anticipated that the film formulations of sildenafil citrate will provide a more compliant and discreet dosage form. The purpose of this clinical study was to compare the bioequivalence of the 2 sildenafil OSF 100 mg formulations (MonoSol Rx, LLC) with the sildenafil citrate 100 mg tablets. The design was a single-dose, randomized, open-label, 3-period, 6-sequence, 3-treatment, single-center, crossover study conducted in 18 healthy, nonsmoking male volunteers under fasting conditions, with each treatment period separated by a 7-day washout period. Plasma sildenafil concentrations were measured predose and then periodically to 24 hours after dosing. The 90% confidence intervals for plasma sildenafil AUC0-t, AUC0-∞, and Cmax for both sildenafil OSF formulations as compared with sildenafil citrate tablets were all within the 80%-125% range, indicating bioequivalence of both film formulations to sildenafil citrate tablets. Overall, the demonstrated bioequivalence coupled with the performance advantages of an OSF dosage form (ie, rapid dissolution in the mouth, can be taken without water, and can be dosed discreetly) suggest that the sildenafil OSF may provide an attractive alternative to sildenafil citrate oral tablets.

  3. Three-way, three-period, crossover bioequivalence study of single oral dose of three brands of 300 mg phenytoin sodium tablets marketed in India, on healthy Indian human volunteers.

    Science.gov (United States)

    Doshi, Maulik S; Naik, Anuja A; Mehta, Mohit R; Gogtay, Nithya J; Thatte, Urmila M; Menon, Mala D

    2013-10-01

    To compare the bioavailability of two brands of phenytoin sodium tablets available in the Indian market using Eptoin™ as the reference. A randomized, assessor-blind, three-way crossover design study was carried out over a period of 6 months after approval from the Institutional Review Board (IRB). Twenty-two healthy male participants received a single oral 300 mg oral tablet of either of the formulations with a 2-week washout. Blood samples were collected predose and at regular intervals postdose. Plasma phenytoin levels were estimated by high-performance liquid chromatography. Calculation of Cmax, AUC0-t, and AUC0-∞ was done by the linear trapezoidal rule and 90-110% margin (90% confidence interval (CI)) was used to assess bioequivalence. Twenty volunteers completed the study. It was seen that the log-transformed values of Cmax, AUC0-t, and AUC0-∞ of the test formulations were not within the specified limits. Bioinequivalence of available phenytoin brands indicates that switching brands could lead to variations in blood concentrations and thus impact safety and efficacy. If a brand switch is done for any reason, stringent drug-level monitoring is advised.

  4. Split high‐dose oral levothyroxine treatment as a successful therapy option in myxedema coma

    OpenAIRE

    Charoensri, Suranut; Sriphrapradang, Chutintorn; Nimitphong, Hataikarn

    2017-01-01

    Key Clinical Message High‐dose intravenous thyroxine (T4) is the preferable treatment for myxedema coma. We describe the clinical course of a 69‐year‐old man who presented with myxedema coma and received oral levothyroxine (LT4) therapy (1 mg) in a split dose. This suggests split high‐dose oral LT4 as a therapeutic option in myxedema coma.

  5. Single dose oral piroxicam for acute postoperative pain

    Science.gov (United States)

    Moore, R Andrew; Edwards, Jayne; Loke, Yoon; Derry, Sheena; McQuay, Henry J

    2014-01-01

    Background This is an updated version of the original Cochrane review published in Issue 2, 2000. Piroxicam is a non-steroidal anti-inflammatory drug (NSAID) with analgesic properties, and is used mainly for treating rheumatic disorders. Some drugs have been directly compared against each other within a trial setting to determine their relative efficacies, whereas other have not. It is possible, however, to compare analgesics indirectly by examining the effectiveness of each drug against placebo when used in similar clinical situations. Objectives To determine the analgesic efficacy and adverse effects of single-dose piroxicam compared with placebo in moderate to severe postoperative pain. To compare the effects of piroxicam with other analgesics. Search methods Published studies were identified from systematic searching of MEDLINE, Biological Abstracts, EMBASE, CENTRAL and the Oxford Pain Relief Database in December 2007. Additional studies were identified from the reference lists of retrieved reports. Selection criteria The following inclusion criteria were used: full journal publication, randomised placebo controlled trial, double-blind design, adult participants, postoperative pain of moderate to severe intensity at the baseline assessment, postoperative administration of oral or intramuscular piroxicam. Data collection and analysis Summed pain intensity and pain relief data were extracted and converted into dichotomous information to yield the number of participants obtaining at least 50% pain relief. This was used to calculate estimates of relative benefit and number-needed-to-treat-to-benefit (NNT) for one participant to obtain at least 50% pain relief. Information was collected on adverse effects and estimates of relative risk and number-needed-to-treat-to-harm (NNH) were calculated. Main results In this update no further studies were found. The original search identified three studies (141 participants) which compared oral piroxicam 20 mg with placebo and

  6. High dose rate brachytherapy for oral cancer

    International Nuclear Information System (INIS)

    Yamazaki, Hideya; Yoshida, Ken; Yoshioka, Yasuo; Shimizutani, Kimishige; Koizumi, Masahiko; Ogawa, Kazuhiko; Furukawa, Souhei

    2013-01-01

    Brachytherapy results in better dose distribution compared with other treatments because of steep dose reduction in the surrounding normal tissues. Excellent local control rates and acceptable side effects have been demonstrated with brachytherapy as a sole treatment modality, a postoperative method, and a method of reirradiation. Low-dose-rate (LDR) brachytherapy has been employed worldwide for its superior outcome. With the advent of technology, high-dose-rate (HDR) brachytherapy has enabled health care providers to avoid radiation exposure. This therapy has been used for treating many types of cancer such as gynecological cancer, breast cancer, and prostate cancer. However, LDR and pulsed-dose-rate interstitial brachytherapies have been mainstays for head and neck cancer. HDR brachytherapy has not become widely used in the radiotherapy community for treating head and neck cancer because of lack of experience and biological concerns. On the other hand, because HDR brachytherapy is less time-consuming, treatment can occasionally be administered on an outpatient basis. For the convenience and safety of patients and medical staff, HDR brachytherapy should be explored. To enhance the role of this therapy in treatment of head and neck lesions, we have reviewed its outcomes with oral cancer, including Phase I/II to Phase III studies, evaluating this technique in terms of safety and efficacy. In particular, our studies have shown that superficial tumors can be treated using a non-invasive mold technique on an outpatient basis without adverse reactions. The next generation of image-guided brachytherapy using HDR has been discussed. In conclusion, although concrete evidence is yet to be produced with a sophisticated study in a reproducible manner, HDR brachytherapy remains an important option for treatment of oral cancer. (author)

  7. High dose rate brachytherapy for oral cancer.

    Science.gov (United States)

    Yamazaki, Hideya; Yoshida, Ken; Yoshioka, Yasuo; Shimizutani, Kimishige; Furukawa, Souhei; Koizumi, Masahiko; Ogawa, Kazuhiko

    2013-01-01

    Brachytherapy results in better dose distribution compared with other treatments because of steep dose reduction in the surrounding normal tissues. Excellent local control rates and acceptable side effects have been demonstrated with brachytherapy as a sole treatment modality, a postoperative method, and a method of reirradiation. Low-dose-rate (LDR) brachytherapy has been employed worldwide for its superior outcome. With the advent of technology, high-dose-rate (HDR) brachytherapy has enabled health care providers to avoid radiation exposure. This therapy has been used for treating many types of cancer such as gynecological cancer, breast cancer, and prostate cancer. However, LDR and pulsed-dose-rate interstitial brachytherapies have been mainstays for head and neck cancer. HDR brachytherapy has not become widely used in the radiotherapy community for treating head and neck cancer because of lack of experience and biological concerns. On the other hand, because HDR brachytherapy is less time-consuming, treatment can occasionally be administered on an outpatient basis. For the convenience and safety of patients and medical staff, HDR brachytherapy should be explored. To enhance the role of this therapy in treatment of head and neck lesions, we have reviewed its outcomes with oral cancer, including Phase I/II to Phase III studies, evaluating this technique in terms of safety and efficacy. In particular, our studies have shown that superficial tumors can be treated using a non-invasive mold technique on an outpatient basis without adverse reactions. The next generation of image-guided brachytherapy using HDR has been discussed. In conclusion, although concrete evidence is yet to be produced with a sophisticated study in a reproducible manner, HDR brachytherapy remains an important option for treatment of oral cancer.

  8. Single and Multiple Ascending-dose Studies of Oral Delafloxacin: Effects of Food, Sex, and Age.

    Science.gov (United States)

    Hoover, Randall; Hunt, Thomas; Benedict, Michael; Paulson, Susan K; Lawrence, Laura; Cammarata, Sue; Sun, Eugene

    2016-01-01

    The objective of this report is describe the results of 2 studies that examined the pharmacokinetic parameters, safety profile, and tolerability of single and multiple ascending doses of oral delafloxacin and the effects of food, sex, and age on oral delafloxacin pharmacokinetic parameters, safety profile, and tolerability. The first study contained 3 parts and used unformulated delafloxacin in a capsule. Part 1 was a randomized, double-blind, placebo-controlled, single (50, 100, 200, 400, 800, 1200, and 1600 mg) ascending-dose study of oral delafloxacin in healthy men. Part 2 was a single-dose crossover study in which 20 men received 250 mg delafloxacin with or without food. Part 2 also included a parallel group, double-blind, placebo-controlled study in 16 women and 16 elderly men and women who were randomized (3:1) to receive 250 mg delafloxacin or placebo. Part 3 was a randomized, double-blind, placebo-controlled, multiple (100, 200, 400, 800, 1200 mg once daily for 5 days) ascending-dose study of oral delafloxacin in healthy men. The second study was a single-dose, randomized, 3-period crossover study in which participants received 900 mg delafloxacin (2 × 450-mg tablets) under fasted conditions, with a high-fat meal, or fasted with a high-fat meal 2 hours after dosing. Serial blood samples were collected, and plasma pharmacokinetic parameters of delafloxacin were determined. Delafloxacin Cmax and AUC0-∞ increased with increasing oral dose over the dose range of 50 to 1600 mg. The increases in delafloxacin AUC0-∞ were dose proportional at doses of ≥200 mg. Steady state was reached by day 3 of dosing with minimal accumulation of delafloxacin. The Cmax of delafloxacin was decreased slightly in the presence of food. No sex difference in delafloxacin pharmacokinetic parameters was observed. In the elderly men and women, mean delafloxacin Cmax and AUC0-∞ were 35% higher than observed for young adults, which could be partially explained by a decrease in

  9. Bioavailability of higher dose methotrexate comparing oral and subcutaneous administration in patients with rheumatoid arthritis

    NARCIS (Netherlands)

    Hoekstra, Monique; Haagsma, C.; Neef, C; Proost, Johannes H; Knuif, A.; van der Laar, M.

    Objective. To determine the bioavailability of higher oral doses of methotrexate (MTX) in adult patients with rheumatoid arthritis (RA). Methods. A pharmacokinetic analysis was performed in 15 patients with RA taking a stable dose of MTX (greater than or equal to25 mg weekly). Separated by 2 weeks,

  10. Preoperative chemoradiotherapy with oral doxifluridine plus low-dose oral leucovorin in unresectable primary rectal cancer

    International Nuclear Information System (INIS)

    Seong, Jinsil; Cho, Jae Ho; Kim, Nam Kyu; Min, Jin Sik; Suh, Chang Ok

    2001-01-01

    Purpose: The use of oral chemotherapeutic agents in chemoradiotherapy provides several advantages. Doxifluridine, an oral 5-FU prodrug, has been shown to be effective in colorectal cancer. We attempted a Phase II trial of preoperative chemoradiotherapy with doxifluridine plus a low-dose oral leucovorin in unresectable primary rectal cancer patients. In this study, toxicity and efficacy were evaluated. Methods and Materials: There were 23 patients with primary unresectable rectal cancer in this trial, 21 of whom were available for analysis. The patients were treated with oral doxifluridine (900 mg/day) plus oral leucovorin (30 mg/day) from days 1 to 35, and pelvic radiation of 45 Gy over 5 weeks. Surgical resection was performed 5-6 weeks after the treatment. Results: Acute toxicity involved thrombocytopenia, nausea/vomiting, diarrhea, and skin reaction. All were in Grade 1/2, except diarrhea, which was not only the most frequent (7 patients, 33.3%), but also the only toxicity of Grade 3 (2 patients). The clinical tumor response was shown in 5 patients (23.8%) as a complete response and 13 patients (61.9%) as a partial response. A complete resection with negative resection margin was done in 18 patients (85.7%), in 2 of whom a pathologic complete response was shown (9.5%). The overall downstaging rate in the T- and N-stage groupings was 71.4% (15 patients). Conclusion: This study demonstrated the efficacy and low toxicity of chemoradiotherapy with doxifluridine. Currently, a Phase III randomized trial of chemoradiotherapy is ongoing at our institute to compare the therapeutic efficacy of oral 5-FU with respect to i.v. 5-FU in locally advanced and unresectable rectal cancer

  11. Comparison of initial loading doses of 5 mg and 10 mg for warfarin therapy

    Directory of Open Access Journals (Sweden)

    Sidnei Lastória

    2014-03-01

    Full Text Available CONTEXT: The question of what is the best loading dosage of warfarin when starting anticoagulant treatment has been under discussion for ten years. We were unable to find any comparative studies of these characteristics conducted here in Brazil. OBJECTIVE: To compare the safety and efficacy of two initial warfarin dosage regimens for anticoagulant treatment. METHODS: One-hundred and ten consecutive patients of both sexes, with indications for anticoagulation because of venous or arterial thromboembolism, were analyzed prospectively. During the first 3 days of treatment, these patients were given adequate heparin to keep aPTT (activated partial thromboplastin time between 1.5 and 2.5, plus 5 mg of warfarin. From the fourth day onwards, their warfarin doses were adjusted using International Normalized Ratios (INR; target range: 2 to 3. This prospective cohort was compared with a historical series of 110 patients had been given 10 mg of warfarin on the first 2 days and 5 mg on the third day with adjustments based on INR thereafter. Outcomes analyzed were as follows: recurrence of thromboembolism, bleeding events and time taken to enter the therapeutic range. RESULTS: Efficacy, safety and length of hospital stay were similar in both samples. The sample that were given 10 mg entered the therapeutic range earlier (means: 4.5 days vs. 5.8 days, were on lower doses at discharge and had better therapeutic indicators at the first return appointment. CONCLUSIONS: The 10 mg dosage regimen took less time to attain the therapeutic range and was associated with lower warfarin doses at discharge and better INR at first out-patients follow-up visit.

  12. Disposition of 2,4-dichlorophenoxyacetic acid dimethylamine by Fischer 344 rats dosed orally and dermally

    International Nuclear Information System (INIS)

    Pelletier, O.; Ritter, L.; Caron, J.; Somers, D.

    1989-01-01

    The dimethylamine salt of 14C-ring-labeled 2,4-D was administered to Fischer 344 rats orally (1 and 0.4 mg/kg body weight) and dermally (10 mg/kg body weight). Absorption, distribution, and elimination were determined from 14C-labeled 2,4-D in blood, tissues, and excreta. Quantitatively, most of the orally administered dose (94-96%) became systemically available within 6 h. Following dermal administration 10% of the dose became systemically available over 72 h. However, peak concentrations in blood and kidneys were achieved within 30 min of dosing by either route. By 1.5 h after dosing, 2,4-D concentrations in blood, muscle, liver, and kidneys had decreased in both the orally dosed and dermally dosed animals. Between 2 and 8 h, the blood, muscle, liver and kidney concentrations in dermally dosed animals maintained a plateau while urinary excretion increased, presumably due to continued absorption of 2,4-D from the skin. The concentrations in orally dosed animals continued to decrease. Following 7 h of dermal exposure, skin cleansing removed about 63% of the applied dose; about 17% of the applied dose remained at the site of dermal dosing. At 8 h, 2,4-D concentrations in blood, muscle, liver, and kidneys of dermally dosed animals began to decrease, most likely a result of the removal of the reservoir on the skin. However, 2,4-D continued to be absorbed from skin site, resulting in a slower decline of the 2,4-D concentrations in these tissues over remainder of the 72-h study period. By comparison, in animals that had been orally dosed, the absorbed dose was almost completely excreted within 24 h

  13. Continuous low-dose oral chemotherapy in recurrent and persistent carcinoma of cervix following chemoradiation: A comparative study between prolonged oral cyclophosphamide and oral etoposide

    Directory of Open Access Journals (Sweden)

    Upasana Baruah

    2014-01-01

    Full Text Available Aim: To compare the efficacy and toxicities of low-dose oral cyclophosphamide and oral etoposide in patients with persistent and recurrent cervical cancer with gross pelvic disease following full course of chemoradiation therapy. Materials and Methods: 30 patients with recurrent and persistent cervical cancer with gross pelvic disease were enrolled in this trial. The patients were randomly divided into two groups of 15 patients each with one group receiving low dose oral cyclophosphamide (100 mg/day and the other group receiving low-dose oral etoposide (50 mg/day. Results were statistically analysed by IBM SPSS Statistics 19. Results: Oral etoposide was not well tolerated with grade 2 neutropenia occurring in 33.3% and grade 3 neutropenia in 6.6% and thrombocytopenia occurring in 13.3%. Oral cyclophosphamide group on the other hand was better tolerated with none of the patients having thrombocytopenia and 6.6% patients having grade 2 neutropenia. There were two complete response (15.38% and one partial response at the end of study (7.6% in the cyclophosphamide group whereas there was no complete response and two partial response (16.6% in the oral etoposide group. Conclusion: Long-term, low-dose oral etoposide was found to be less tolerated without any significant effect with patients with persistent and recurrent cervical cancer with gross pelvic disease following full course of chemoradiation therapy in contrast to oral cyclophosphamide which was found to be effective and well-tolerated by the patients.

  14. Mouse single oral dose toxicity test of bupleuri radix aqueous extracts.

    Science.gov (United States)

    Kim, Kyung-Hu; Gam, Cheol-Ou; Choi, Seong-Hun; Ku, Sae-Kwang

    2012-03-01

    The aim of this study was to evaluate the single oral dose toxicity of Bupleuri Radix (BR) aqueous extracts, it has been traditionally used as anti-inflammatory agent, in male and female mice. BR extracts (yield = 16.52%) was administered to female and male ICR mice as an oral dose of 2,000, 1,000 and 500 mg/kg (body weight) according to the recommendation of Korea Food and Drug Administration (KFDA) Guidelines. Animals were monitored for the mortality and changes in body weight, clinical signs and gross observation during 14 days after dosing, upon necropsy; organ weight and histopathology of 14 principal organs were examined. As the results, no BR extracts treatment related mortalities, clinical signs, changes on the body and organ weights, gross and histopathological observations against 14 principal organs were detected up to 2,000 mg/kg in both female and male mice, except for soft feces and related body weight decrease detected in male mice treated with 2,000 mg/kg. Therefore, LD50 (50% lethal dose) and approximate LD of BR aqueous extracts after single oral treatment in female and male mice were considered over 2000 mg/kg, respectively. Although it was also observed that the possibilities of digestive disorders, like soft feces when administered over 2,000 mg/kg of BR extracts in the present study, these possibilities of digestive disorders can be disregard in clinical use because they are transient in the highest dosages male only.

  15. Oral pulsed high-dose dexamethasone for myositis

    NARCIS (Netherlands)

    van der Meulen, M. F.; Hoogendijk, J. E.; Wokke, J. H.; de Visser, M.

    2000-01-01

    To study the short-term effect of oral pulsed high-dose dexamethasone for myositis we treated eight newly diagnosed patients with three 28-day cycles of oral dexamethasone. Primary outcome measures were muscle strength, pain, and serum creatine kinase activity. Six patients responded. Side effects

  16. [Individualization of low-dose oral contraceptives. Pharmacological principles and practical indications for oral contraceptives].

    Science.gov (United States)

    Cianci, A; De Leo, V

    2007-08-01

    water retention, weight gain and arterial hypertension often associated with oral contraceptive use. Recent comparative studies recorded weight loss that stabilized after 6 months of treatment with drospirenone/EE. Overweight women may therefore benefit from the formulation with 20 microg EE, whereas the formulation with at least 30 microg EE should be more appropriate for underweight women. Women with slight to moderate acne, the formulation with 30 microg EE has been found to be as effective as 2 mg cyproterone acetate combined with 35 micrig EE (Diane). Menstrual cycle characteristics, however, remain the main factor determining the choice of formulation. Randomised control studies comparing the new formulation with others containing second or third generation progesterones have found similar efficacy in cycle control and incidence of spotting. From this point of view, it is not advisable to prescribe more than 30 microg EE (Yasmin or Yasminelle) for women with normal menstrual cycles, whereas in cases of hypomenorrhea and/or amenorrhea at least this dose of EE plus drospirenone may be used. Women with hypermenorrhea run the risk of spotting if an inappropriate drug is chosen. A solution is to use 30 microg EE/drospirenone from day 5 of the cycle. To control so-called minor side-effects, the dose of EE must be appropriate. In women with premenstrual tension a dose of at least 30 microg EE associated with drospirenone reduces or even prevents symptoms. On the other hand, in cases of chronic headache or headache as a side-effect of oral contraceptive use, a lower dose of estrogen is beneficial, and doses below 20 microg may be used. Although the progesterone component is not considered to affect headache, good results have been obtained with drospirenone, the antimineralcorticoid effects of which reduce blood pressure and improve symptoms. Formulations with 20 microg EE and drospirenone are particularly indicated in women with pre-existing mastodynia, fibrocystic

  17. Phototransfered thermoluminescence for dose reassessment in LiF:mg,ti , LiF: mg,Cu,p TL detectors

    International Nuclear Information System (INIS)

    Rodriguez Otazo, M.; Baly, L.

    2001-01-01

    Phototransfered Thermoluminescence (PTTL) from LiF:Mg,Ti (TLD-100) and LiF: Mg,Cu,P (GR-200) was studied at different conditions using different sources of UV light for dose reassessment purposes. The TL dosimeters were irradiated with 137Cs in the range 2 mGy to 100 mGy. The convenience of using PTTL for dose reassessment was analyzed

  18. Bioavailibility of higher dose methotrexate comparing oral and subcutaneous route of administration in patients with rheumatoid arthritis

    NARCIS (Netherlands)

    Hoekstra, Monique; Hoekstra, M.; Haagsma, Cees; Neef, Cees; Proost, Johannes; van de Laar, Mart A F J; Knuif, Antonius

    2004-01-01

    OBJECTIVE: To determine the bioavailability of higher oral doses of methotrexate (MTX) in adult patients with rheumatoid arthritis (RA). METHODS: A pharmacokinetic analysis was performed in 15 patients with RA taking a stable dose of MTX (> or = 25 mg weekly). Separated by 2 weeks, a pharmacokinetic

  19. Single dose oral ketoprofen and dexketoprofen for acute postoperative pain in adults.

    Science.gov (United States)

    Barden, Jodie; Derry, Sheena; McQuay, Henry J; Moore, R Andrew

    2009-10-07

    Ketoprofen is a non-selective non-steroidal anti-inflammatory drug (NSAID) used to treat acute and chronic painful conditions. Dexketoprofen is the (S)-enantiomer, which is believed to confer analgesia. Theoretically dexketoprofen is expected to provide equivalent analgesia to ketoprofen at half the dose, with a consequent reduction in gastrointestinal adverse events. To assess efficacy, duration of action, and associated adverse events of single dose oral ketoprofen and dexketoprofen in acute postoperative pain in adults. We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies to August 2009. Randomised, double blind, placebo-controlled trials of single dose orally administered ketoprofen and dexketoprofen in adults with moderate to severe acute postoperative pain. Two review authors independently assessed trial quality and extracted data. Pain relief or pain intensity data were extracted and converted into the dichotomous outcome of number of participants with at least 50% pain relief over 4 to 6 hours, from which relative risk and number-needed-to-treat-to-benefit (NNT) were calculated. Numbers of participants using rescue medication over specified time periods, and time to use of rescue medication, were sought as additional measures of efficacy. Information on adverse events and withdrawals was collected. Fourteen studies compared ketoprofen (968 participants) at mainly 25 mg and 50 mg with placebo (520 participants). Seven studies compared dexketoprofen (681 participants) at mainly 10 mg to 25 mg with placebo (289 participants). Studies were of adequate reporting quality, and participants had pain following dental, orthopaedic, obstetric, gynaecological and general surgery. There was considerable clinical heterogeneity between studies in dental and other types of surgery, particularly bunionectomy, which limited analysis.Ketoprofen at doses between 12.5 mg and 100 mg produced NNTs for at least 50% pain relief over 4 to 6

  20. Pharmacokinetics of terbinafine after oral administration of a single dose to Hispaniolan Amazon parrots (Amazona ventralis).

    Science.gov (United States)

    Evans, Erika E; Emery, Lee C; Cox, Sherry K; Souza, Marcy J

    2013-06-01

    To determine pharmacokinetics after oral administration of a single dose of terbinafine hydrochloride to Hispaniolan Amazon parrots (Amazona ventralis). 6 healthy adult Hispaniolan Amazon parrots. A single dose of terbinafine hydrochloride (60 mg/kg) was administered orally to each bird, which was followed immediately by administration of a commercially available gavage feeding formula. Blood samples were collected at the time of drug administration (time 0) and 0.25, 0.5, 1, 2, 4, 8, 12, and 24 hours after drug administration. Plasma concentrations of terbinafine were determined via high-performance liquid chromatography. Data from 1 bird were discarded because of a possible error in the dose of drug administered. After oral administration of terbinafine, the maximum concentration for the remaining 5 fed birds ranged from 109 to 671 ng/mL, half-life ranged from 6 to 13.5 hours, and time to the maximum concentration ranged from 2 to 8 hours. No adverse effects were observed. Analysis of the results indicated that oral administration of terbinafine at a dose of 60 mg/kg to Amazon parrots did not result in adverse effects and may be potentially of use in the treatment of aspergillosis. Additional studies are needed to determine treatment efficacy and safety.

  1. Effect of repeated oral therapeutic doses of methylphenidate on food intake and growth rate in rats.

    Science.gov (United States)

    Alam, Nausheen; Najam, Rahila

    2015-01-01

    Central nervous system stimulants are known to produce anorexia. Previous data suggest that methylphenidate can have variable effects on caloric intake and growth rate. A dose-response study was performed to monitor caloric intake, liquid intake and growth rate in rats following repeated administration of human oral therapeutic doses 2 mg/kg/day, 5mg/kg/day and 8mg/kg/day of methylphenidate. We found that food intake and water intake, increased in all weeks and at all doses used in the study. Growth rate increased more at higher dose (8mg/kg/day) and at low dose (2mg/kg/day) of methylphenidate in 1(st) and 2(nd) week whereas more decreased by the above doses in 3(rd) week, suggesting that food stimulation leads to initial increase in growth rate but long term administration of methylphenidate attenuate growth rate that is not due to modulation of appetite but may be due to anxiety and increased activity produce by stimulants. A possible role of DA, 5HT receptors in modulation of appetite and anxiety is discussed.

  2. Pharmacokinetics after oral and intravenous administration of a single dose of tramadol hydrochloride to Hispaniolan Amazon parrots (Amazona ventralis).

    Science.gov (United States)

    Souza, Marcy J; Sanchez-Migallon Guzman, David; Paul-Murphy, Joanne R; Cox, Sherry K

    2012-08-01

    To determine pharmacokinetics after IV and oral administration of a single dose of tramadol hydrochloride to Hispaniolan Amazon parrots (Amazona ventralis). 9 healthy adult Hispaniolan Amazon parrots (3 males, 5 females, and 1 of unknown sex). Tramadol (5 mg/kg, IV) was administered to the parrots. Blood samples were collected from -5 to 720 minutes after administration. After a 3-week washout period, tramadol (10 and 30 mg/kg) was orally administered to parrots. Blood samples were collected from -5 to 1,440 minutes after administration. Three formulations of oral suspension (crushed tablets in a commercially available suspension agent, crushed tablets in sterile water, and chemical-grade powder in sterile water) were evaluated. Plasma concentrations of tramadol and its major metabolites were measured via high-performance liquid chromatography. Mean plasma tramadol concentrations were > 100 ng/mL for approximately 2 to 4 hours after IV administration of tramadol. Plasma concentrations after oral administration of tramadol at a dose of 10 mg/kg were 100 ng/mL for approximately 6 hours after administration. Oral administration of the suspension consisting of the chemical-grade powder resulted in higher plasma tramadol concentrations than concentrations obtained after oral administration of the other 2 formulations; however, concentrations differed significantly only at 120 and 240 minutes after administration. Oral administration of tramadol at a dose of 30 mg/kg resulted in plasma concentrations (> 100 ng/mL) that have been associated with analgesia in Hispaniolan Amazon parrots.

  3. Protective effects of orally applied fullerenol nano particles in rats after a single dose of doxorubicin

    Directory of Open Access Journals (Sweden)

    Ičević Ivana Đ.

    2011-01-01

    Full Text Available Polyhydroxylated, water soluble, fullerenol C60(OH24 nano particles (FNP in vitro and in vivo models, showed an expressive biological activity. The goal of this work was to investigate the potential protective effects of orally applied FNP on rats after a single dose of doxorubicin (DOX (8 mg/kg (i.p. 6 h after the last application of FNP. After the last drug administration, the rats were sacrificed, and the blood and tissues were taken for the analysis. Biochemical and pathological results obtained in this study indicate that fullerenol (FNP, in H2O:DMSO (80:20, w/w solution given orally in final doses of 10, 14.4, and 21.2 mg/kg three days successively, has the protective (hepatoprotective and nephroprotective effect against doxorubicin-induced cytotoxicity via its antioxidant properties.

  4. PHARMACOKINETICS OF SINGLE-DOSE ORALLY ADMINISTERED CIPROFLOXACIN IN CALIFORNIA SEA LIONS (ZALOPHUS CALIFORNIANUS).

    Science.gov (United States)

    Barbosa, Lorraine; Johnson, Shawn P; Papich, Mark G; Gulland, Frances

    2015-06-01

    Ciprofloxacin is commonly selected for clinical use due to its broad-spectrum efficacy and is a frequently administered antibiotic at The Marine Mammal Center, a marine mammal rehabilitation facility. Ciprofloxacin is used for treatment of California sea lions ( Zalophus californianus ) suffering from a variety of bacterial infections at doses extrapolated from other mammalian species. However, as oral absorption is variable both within and across species, a more accurate determination of appropriate dosage is needed to ensure effective treatment and avoid emergence of drug-resistant bacterial strains. A pharmacokinetic study was performed to assess plasma concentrations of ciprofloxacin in California sea lions after a single oral dose. Twenty healthy California sea lions received a single 10-mg/kg oral dose of ciprofloxacin administered in a herring fish. Blood was then collected at two of the following times from each individual: 0.5, 0.75, 1, 2, 4, 8, 10, 12, 18, and 24 hr postingestion. Plasma ciprofloxacin concentration was assessed via high-performance liquid chromatography. A population pharmacokinetics model demonstrated that an oral ciprofloxacin dose of 10 mg/kg achieved an area under the concentration vs. time curve of 6.01 μg hr/ml. Absorption was rapid, with ciprofloxacin detectable in plasma 0.54 hr after drug administration; absorption half-life was 0.09 hr. A maximum plasma concentration of 1.21 μg/ml was observed at 1.01 hr, with an elimination half-life of 3.09 hr. Ciprofloxacin administered orally at 10 mg/kg produced therapeutic antibacterial exposure for only some of the most susceptible bacterial organisms commonly isolated from California sea lions.

  5. Single oral dose toxicity test of platycodin d, a saponin from platycodin radix in mice.

    Science.gov (United States)

    Lee, Won-Ho; Gam, Cheol-Ou; Ku, Sae-Kwang; Choi, Seong-Hun

    2011-12-01

    The object of this study was to evaluate the single oral dose toxicity of platycodin D, a saponin from the root of Platycodon grandiflorum in male and female mice. Platycodin D was administered to female and male mice as an oral dose of 2000, 1000, 500, 250 and 125 mg/kg (body wt.). Animals were monitored for the mortality and changes in body weight, clinical signs and gross observation during 14 days after treatment, upon necropsy, organ weight and histopathology of 14 principle organs were examined. As the results, no platycodin D treatment related mortalities, clinical signs, changes on the body and organ weights, gross and histopathological observations against 14 principle organs were detected up to 2000 mg/kg in both female and male mice. Therefore, LD50 (50% lethal dose) and approximate LD of playtcodin D after single oral treatment in female and male mice were considered over 2000 mg/kg - the limited dosages recommended by KFDA Guidelines [2009-116, 2009], respectively.

  6. The effect of high-dose dronabinol (oral THC) maintenance on cannabis self-administration.

    Science.gov (United States)

    Schlienz, Nicolas J; Lee, Dustin C; Stitzer, Maxine L; Vandrey, Ryan

    2018-06-01

    There is a clear need for advancing the treatment of cannabis use disorders. Prior research has demonstrated that dronabinol (oral THC) can dose-dependently suppress cannabis withdrawal and reduce the acute effects of smoked cannabis. The present study was conducted to evaluate whether high-dose dronabinol could reduce cannabis self-administration among daily users. Non-treatment seeking daily cannabis users (N = 13) completed a residential within-subjects crossover study and were administered placebo, low-dose dronabinol (120 mg/day; 40 mg tid), or high-dose dronabinol (180-240 mg/day; 60-80 mg tid) for 12 consecutive days (order counterbalanced). During each 12-day dronabinol maintenance phase, participants were allowed to self-administer smoked cannabis containing <1% THC (placebo) or 5.7% THC (active) under forced-choice (drug vs. money) or progressive ratio conditions. Participants self-administered significantly more active cannabis compared with placebo in all conditions. When active cannabis was available, self-administration was significantly reduced during periods of dronabinol maintenance compared with placebo maintenance. There was no difference in self-administration between the low- and high-dose dronabinol conditions. Chronic dronabinol dosing can reduce cannabis self-administration in daily cannabis users and suppress withdrawal symptoms. Cannabinoid agonist medications should continue to be explored for therapeutic utility in the treatment of cannabis use disorders. Copyright © 2018 Elsevier B.V. All rights reserved.

  7. Warfarin Dosing Algorithms Underpredict Dose Requirements in Patients Requiring ≥7 mg Daily: A Systematic Review and Meta-analysis.

    Science.gov (United States)

    Saffian, S M; Duffull, S B; Wright, Dfb

    2017-08-01

    There is preliminary evidence to suggest that some published warfarin dosing algorithms produce biased maintenance dose predictions in patients who require higher than average doses. We conducted a meta-analysis of warfarin dosing algorithms to determine if there exists a systematic under- or overprediction of dose requirements for patients requiring ≥7 mg/day across published algorithms. Medline and Embase databases were searched up to September 2015. We quantified the proportion of over- and underpredicted doses in patients whose observed maintenance dose was ≥7 mg/day. The meta-analysis included 47 evaluations of 22 different warfarin dosing algorithms from 16 studies. The meta-analysis included data from 1,492 patients who required warfarin doses of ≥7 mg/day. All 22 algorithms were found to underpredict warfarin dosing requirements in patients who required ≥7 mg/day by an average of 2.3 mg/day with a pooled estimate of underpredicted doses of 92.3% (95% confidence interval 90.3-94.1, I 2 = 24%). © 2017 American Society for Clinical Pharmacology and Therapeutics.

  8. Pharmacokinetics of sulfamethoxazole and trimethoprim in Pacific white shrimp, Litopenaeus vannamei, after oral administration of single-dose and multiple-dose.

    Science.gov (United States)

    Ma, Rongrong; Wang, Yuan; Zou, Xiong; Hu, Kun; Sun, Beibei; Fang, Wenhong; Fu, Guihong; Yang, Xianle

    2017-06-01

    The tissue distribution and depletion of sulfamethoxazole (SMZ) and trimethoprim (TMP) were studied in Pacific white shrimp, Litopenaeus vannamei, after single-dose and multiple-dose oral administration of SMZ-TMP (5:1) via medicated feed. In single-dose oral administration, shrimps were fed once at a dose of 100 mg/kg (drug weight/body weight). In multiple-dose oral administration, shrimps were fed three times a day for three consecutive days at a dose of 100mg/kg. The results showed the kinetic characteristic of SMZ was different from TMP in Pacific white shrimp. In the single-dose administration, the SMZ was widely distributed in the tissues, while TMP was highly concentrated in the hepatopancreas. The t 1/2z values of SMZ were larger and persist longer than TMP in Pacific white shrimp. In the multiple-dose administration, SMZ accumulated well in the tissues, and reached steady state level after successive administrations, while TMP did not. TMP concentration even appeared the downward trend with the increase of drug times. Compared with the single dose, the t 1/2z values of SMZ in hepatopancreas (8.22-11.33h) and muscle (6.53-10.92h) of Pacific white shrimps rose, but the haemolymph dropped (13.76-11.03) in the multiple-dose oral administration. Meanwhile, the corresponding values of TMP also rose in hepatopancreas (4.53-9.65h) and muscle (2.12-2.71h), and declined in haemolymph (7.38-5.25h) following single-dose and multiple-dose oral administration in Pacific white shrimps. In addition, it is worth mentioning that the ratios of SMZ and TMP were unusually larger than the general aim ratio. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Pharmacokinetics of voriconazole after oral administration of single and multiple doses in African grey parrots (Psittacus erithacus timneh).

    Science.gov (United States)

    Flammer, Keven; Nettifee Osborne, Julie A; Webb, Donna J; Foster, Laura E; Dillard, Stacy L; Davis, Jennifer L

    2008-01-01

    To determine the pharmacokinetics and safety of orally administered voriconazole in African grey parrots. 20 clinically normal Timneh African grey parrots (Psittacus erithacus timneh). In single-dose trials, 12 parrots were each administered 6, 12, and 18 mg of voriconazole/kg orally and plasma concentrations of voriconazole were determined via high-pressure liquid chromatography. In a multiple-dose trial, voriconazole (18 mg/kg) was administered orally to 6 birds every 12 hours for 9 days; a control group (2 birds) received tap water. Treatment effects were assessed via observation, clinicopathologic analyses (3 assessments), and measurement of trough plasma voriconazole concentrations (2 assessments). Voriconazole's elimination half-life was short (1.1 to 1.6 hours). Higher doses resulted in disproportional increases in the maximum plasma voriconazole concentration and area under the curve. Trough plasma voriconazole concentrations achieved in the multiple-dose trial were lower than those achieved after administration of single doses. Polyuria (the only adverse treatment effect) developed in treated and control birds but was more severe in the treatment group. In African grey parrots, voriconazole has dose-dependent pharmacokinetics and may induce its own metabolism. Oral administration of 12 to 18 mg of voriconazole/kg twice daily is a rational starting dose for treatment of African grey parrots infected with Aspergillus or other fungal organisms that have a minimal inhibitory concentration for voriconazole treatment. Safety and efficacy of various voriconazole treatment regimens in this species require investigation.

  10. Miltefosine Lipid Nanocapsules for Single Dose Oral Treatment of Schistosomiasis Mansoni: A Preclinical Study.

    Directory of Open Access Journals (Sweden)

    Maha M Eissa

    Full Text Available Miltefosine (MFS is an alkylphosphocholine used for the local treatment of cutaneous metastases of breast cancer and oral therapy of visceral leishmaniasis. Recently, the drug was reported in in vitro and preclinical studies to exert significant activity against different developmental stages of schistosomiasis mansoni, a widespread chronic neglected tropical disease (NTD. This justified MFS repurposing as a potential antischistosomal drug. However, five consecutive daily 20 mg/kg doses were needed for the treatment of schistosomiasis mansoni in mice. The present study aims at enhancing MFS efficacy to allow for a single 20mg/kg oral dose therapy using a nanotechnological approach based on lipid nanocapsules (LNCs as oral nanovectors. MFS was incorporated in LNCs both as membrane-active structural alkylphospholipid component and active antischistosomal agent. MFS-LNC formulations showed high entrapment efficiency (EE%, good colloidal properties, sustained release pattern and physical stability. Further, LNCs generally decreased MFS-induced erythrocyte hemolytic activity used as surrogate indicator of membrane activity. While MFS-free LNCs exerted no antischistosomal effect, statistically significant enhancement was observed with all MFS-LNC formulations. A maximum effect was achieved with MFS-LNCs incorporating CTAB as positive charge imparting agent or oleic acid as membrane permeabilizer. Reduction of worm load, ameliorated liver pathology and extensive damage of the worm tegument provided evidence for formulation-related efficacy enhancement. Non-compartmental analysis of pharmacokinetic data obtained in rats indicated independence of antischistosomal activity on systemic drug exposure, suggesting possible gut uptake of the stable LNCs and targeting of the fluke tegument which was verified by SEM. The study findings put forward MFS-LNCs as unique oral nanovectors combining the bioactivity of MFS and biopharmaceutical advantages of LNCs

  11. Single, 14-Day, and 13-Week Repeated Dose Toxicity Studies of Daily Oral Gelidium elegans Extract Administration to Rats.

    Science.gov (United States)

    Choi, Jia; Ryu, Su-Jung; Kim, Kui-Jin; Kim, Hyung-Min; Chung, Hee-Chul; Lee, Boo-Yong

    2018-01-20

    Gelidium elegans extract (GEE) is derived from a red alga from the Asia-Pacific region, which has antioxidant, anti-adipogenic, and anti-hyperglycemic effects. However, detailed studies of the toxicology of GEE have not been performed. We evaluated the single oral dose toxicity of GEE in male and female Sprague-Dawley (CD) rats. GEE did not cause deaths or have toxic effects at dosages of 5000 mg/kg/day, although compound-colored stools and diarrhea were observed in both sexes, which lasted 5000 mg/kg. We next evaluated the repeated oral dose toxicity of GEE in CD rats over 14 days and 13 weeks. GEE did not induce any significant toxicological changes in either sex at 2000 mg/kg/day. Repeated oral dose toxicity studies showed no adverse effects, in terms of clinical signs, mortality, body mass, food consumption, ophthalmic examination, urinalysis, hematology, serum biochemistry, necropsy, organ masses, or histopathology, at dosages of 500, 1000, or 2000 mg/kg/day. The no observed adverse effect level (NOAEL) for GEE is thus likely to be >2000 mg/kg/day, and no pathology was identified in potential target organs. Therefore, this study indicates that repeated oral dosing with GEE is safe in CD rats.

  12. Single, 14-Day, and 13-Week Repeated Dose Toxicity Studies of Daily Oral Gelidium elegans Extract Administration to Rats

    Directory of Open Access Journals (Sweden)

    Jia Choi

    2018-01-01

    Full Text Available Gelidium elegans extract (GEE is derived from a red alga from the Asia–Pacific region, which has antioxidant, anti-adipogenic, and anti-hyperglycemic effects. However, detailed studies of the toxicology of GEE have not been performed. We evaluated the single oral dose toxicity of GEE in male and female Sprague-Dawley (CD rats. GEE did not cause deaths or have toxic effects at dosages of 5000 mg/kg/day, although compound-colored stools and diarrhea were observed in both sexes, which lasted <2 days. Therefore, the LD50 of GEE is likely to be >5000 mg/kg. We next evaluated the repeated oral dose toxicity of GEE in CD rats over 14 days and 13 weeks. GEE did not induce any significant toxicological changes in either sex at 2000 mg/kg/day. Repeated oral dose toxicity studies showed no adverse effects, in terms of clinical signs, mortality, body mass, food consumption, ophthalmic examination, urinalysis, hematology, serum biochemistry, necropsy, organ masses, or histopathology, at dosages of 500, 1000, or 2000 mg/kg/day. The no observed adverse effect level (NOAEL for GEE is thus likely to be >2000 mg/kg/day, and no pathology was identified in potential target organs. Therefore, this study indicates that repeated oral dosing with GEE is safe in CD rats.

  13. Vaxchora: A Single-Dose Oral Cholera Vaccine.

    Science.gov (United States)

    Cabrera, Adriana; Lepage, Jayne E; Sullivan, Karyn M; Seed, Sheila M

    2017-07-01

    To review trials evaluating the efficacy and safety of Vaxchora, a reformulated, single-dose, oral, lyophilized Vibrio cholerae CVD 103-HgR vaccine for the prevention of travel-related cholera caused by V cholerae serogroup O1. A literature search was conducted using MEDLINE (1946 to January week 3, 2017) and EMBASE (1996 to 2017 week 3). Keywords included oral cholera vaccine, single-dose, Vaxchora, and CVD 103-HgR. Limits included human, clinical trials published in English since 2010. ClinicalTrials.gov was used as a source for unpublished data. Additional data sources were obtained through bibliographic review of selected articles. Studies that addressed the safety and efficacy of Vaxchora, the reformulated, single-dose oral CVD 103-HgR cholera vaccine, were selected for analysis. Approval of Vaxchora, was based on efficacy of the vaccine in human trials demonstrating 90.3% protection among those challenged with V cholerae 10 days after vaccination and in immunogenicity studies with 90% systemic vibriocidal antibody conversion at 6 months after a single-dose of vaccine. Tolerability was acceptable, with the most common adverse effects reported to be fatigue, headache, and abdominal pain. Vaxchora is the only FDA-approved, single-dose oral vaccine for the prevention of cholera caused by V cholerae serogroup O1 in adult travelers from the United States going to cholera-affected areas. Safety and efficacy has not been established in children, immunocompromised persons, and pregnant or breastfeeding women or those living in cholera-endemic areas.

  14. Quality control and stability study of 100 mg/ml paracetamol oral drops

    International Nuclear Information System (INIS)

    Garcia Penna, Caridad M.; Montes de Oca Porto, Yanet; Salomon Izquierdo, Suslebys

    2013-01-01

    Paracetamol is an effective analgesic and antipyretic drug of the non-steroidal anti-inflammatory drug group. Paracetamol oral drops are indicated for use in infant population aged up to 5 years to relieve fever, headache, toothache and symptomatic relief of common cold. To validate two analytical methods for the quality control and the stability study and to study the stability of 100 mg/ml Paracetamol oral drops made in Cuba

  15. Single dose oral ketoprofen or dexketoprofen for acute postoperative pain in adults.

    Science.gov (United States)

    Gaskell, Helen; Derry, Sheena; Wiffen, Philip J; Moore, R Andrew

    2017-05-25

    % of the maximum possible pain relief over six hours, the median time to use of rescue medication, and the proportion of participants requiring rescue medication. We also collected information on adverse events and withdrawals. We assessed the quality of the evidence using GRADE, and created 'Summary of findings' tables. This updated review included 24 studies; six additional studies added 1001 participants involved in comparisons of ketoprofen or dexketoprofen and placebo, with a 12% increase in participants taking ketoprofen and a 65% increase for dexketoprofen. Most participants (70%) were women. Dental studies typically involved young participants (mean age 20 to 30 years); other types of surgery involved older participants (mean age 37 to 68 years). Overall, we judged the studies at high risk of bias only for small size, which can lead to an overestimation of benefit.Ketoprofen doses ranged between 6.5 mg and 150 mg. The proportion of participants achieving at least 50% pain relief over six hours with the usual ketoprofen oral dose of 50 mg was 57%, compared to 23% with placebo, giving an NNT of 2.9 (95% CI 2.4 to 3.7) (RR 2.5, 95% CI 2.0 to 3.1; 594 participants; 8 studies; high quality evidence). Efficacy was significantly better in dental studies (NNT 1.8) than other surgery (NNT 4.2). The proportion of participants using rescue medication within six hours was lower with ketoprofen (32%) than with placebo (75%), giving a number needed to treat to prevent use of rescue medication (NNTp) of 2.3 (95% CI 1.8 to 3.1); 263 participants; 4 studies; high quality evidence). Median time to remedication estimates were poorly reported. Reports of any adverse event were similar with ketoprofen (18%) and placebo (11%) (RR 1.6, 95% CI 0.98 to 2.8; 342 participants; 5 studies; high quality evidence). No study reported any serious adverse events (very low quality evidence).Dexketoprofen doses ranged between 5 mg and 100 mg. The proportion of participants achieving at least 50

  16. Guaifenesin Pharmacokinetics Following Single‐Dose Oral Administration in Children Aged 2 to 17 Years

    Science.gov (United States)

    Thompson, Gary A.; Solomon, Gail; Albrecht, Helmut H.; Reitberg, Donald P.

    2016-01-01

    Abstract This study characterized guaifenesin pharmacokinetics in children aged 2 to 17 years (n = 40) who received a single oral dose of guaifenesin (age‐based doses of 100‐400 mg) 2 hours after breakfast. Plasma samples were obtained before and for 8 hours after dosing and analyzed for guaifenesin using liquid chromatography‐tandem mass spectrometry. Pharmacokinetic parameters were estimated using noncompartmental methods, relationships with age were assessed using linear regression, and dose proportionality was assessed on 95% confidence intervals. Based on the upper dose recommended in the monograph (for both children and adolescents), area under the curve from time zero to infinity and maximum plasma concentration both increased with age. However, when comparing the upper dose for children aged 2 to 11 years with the lower dose for adolescents aged 12 to 17 years, similar systemic exposure was observed. As expected due to increasing body size, oral clearance (CLo) and terminal volume of distribution (Vz/F) increased with age. Due to a larger increase in Vz/F than CLo, an increase in terminal exponential half‐life was also observed. Allometric scaling indicated no maturation‐related changes in CLo and Vz/F. PMID:26632082

  17. The effects of intranasal esketamine (84 mg) and oral mirtazapine (30 mg) on on-road driving performance: a double-blind, placebo-controlled study.

    Science.gov (United States)

    van de Loo, Aurora J A E; Bervoets, Adriana C; Mooren, Loes; Bouwmeester, Noor H; Garssen, Johan; Zuiker, Rob; van Amerongen, Guido; van Gerven, Joop; Singh, Jaskaran; der Ark, Peter Van; Fedgchin, Maggie; Morrison, Randall; Wajs, Ewa; Verster, Joris C

    2017-11-01

    The purpose of this study is to evaluate the single dose effect of intranasal esketamine (84 mg) compared to placebo on on-road driving performance. Mirtazapine (oral, 30 mg) was used as a positive control, as this antidepressant drug is known to negatively affect driving performance. Twenty-six healthy volunteers aged 21 to 60 years were enrolled in this study. In the evening, 8 h after treatment administration, participants conducted the standardized 100-km on-road driving test. Primary outcome measure was the standard deviation of lateral position (SDLP), i.e., the weaving of the car. Mean lateral position, mean speed, and standard deviation of speed were secondary outcome measures. For SDLP, non-inferiority analyses were conducted, using +2.4 cm (relative to placebo) as a predefined non-inferiority margin for clinical relevant impairment. Twenty-four participants completed the study. No significant SDLP difference was found between esketamine and placebo (p = 0.7638), whereas the SDLP after mirtazapine was significantly higher when compared to placebo (p = 0.0001). The upper limit of the two-sided 95% confidence interval (CI) of the mean difference between esketamine and placebo was +0.86 cm, i.e., deviation of speed, and mean lateral position were observed between the active treatments and placebo. No significant difference in driving performance was observed 8 h after administering intranasal esketamine (84 mg) or placebo. In contrast, oral mirtazapine (30 mg) significantly impaired on road driving performance.

  18. Pharmacokinetics of orally administered low-dose rapamycin in healthy dogs.

    Science.gov (United States)

    Larson, Jeanne C; Allstadt, Sara D; Fan, Timothy M; Khanna, Chand; Lunghofer, Paul J; Hansen, Ryan J; Gustafson, Daniel L; Legendre, Alfred M; Galyon, Gina D; LeBlanc, Amy K; Martin-Jimenez, Tomas

    2016-01-01

    To determine the pharmacokinetics of orally administered rapamycin in healthy dogs. 5 healthy purpose-bred hounds. The study consisted of 2 experiments. In experiment 1, each dog received rapamycin (0.1 mg/kg, PO) once; blood samples were obtained immediately before and at 0.5, 1, 2, 4, 6, 12, 24, 48, and 72 hours after administration. In experiment 2, each dog received rapamycin (0.1 mg/kg, PO) once daily for 5 days; blood samples were obtained immediately before and at 3, 6, 24, 27, 30, 48, 51, 54, 72, 75, 78, 96, 96.5, 97, 98, 100, 102, 108, 120, 144, and 168 hours after the first dose. Blood rapamycin concentration was determined by a validated liquid chromatography-tandem mass spectrometry assay. Pharmacokinetic parameters were determined by compartmental and noncompartmental analyses. Mean ± SD blood rapamycin terminal half-life, area under the concentration-time curve from 0 to 48 hours after dosing, and maximum concentration were 38.7 ± 12.7 h, 140 ± 23.9 ng•h/mL, and 8.39 ± 1.73 ng/mL, respectively, for experiment 1, and 99.5 ± 89.5 h, 126 ± 27.1 ng•h/mL, and 5.49 ± 1.99 ng/mL, respectively, for experiment 2. Pharmacokinetic parameters for rapamycin after administration of 5 daily doses differed significantly from those after administration of 1 dose. Results indicated that oral administration of low-dose (0.1 mg/kg) rapamycin to healthy dogs achieved blood concentrations measured in nanograms per milliliter. The optimal dose and administration frequency of rapamcyin required to achieve therapeutic effects in tumor-bearing dogs, as well as toxicity after chronic dosing, need to be determined.

  19. Pharmacokinetics of orally administered low-dose rapamycin in healthy dogs: A pilot study

    Science.gov (United States)

    Larson, Jeanne C.; Allstadt, Sara D.; Fan, Timothy M.; Khanna, Chand; Lunghofer, Paul J.; Hansen, Ryan J.; Gustafson, Daniel L.; Legendre, Alfred M.; Galyon, Gina D.; LeBlanc, Amy K.; Martin-Jimenez, Tomas

    2017-01-01

    Objective To determine the pharmacokinetics of orally administered rapamycin in healthy dogs. Animals 5 healthy purpose-bred hounds. Procedures The study consisted of 2 experiments. In experiment 1, each dog received rapamycin (0.1 mg/kg, PO) once; blood samples were obtained immediately before and at 0.5, 1, 2, 4, 6, 12, 24, 48, and 72 hours after administration. In experiment 2, each dog received (0.1 mg/kg, PO) once daily for 5 days; blood samples were obtained immediately before and at 3, 6, 24, 27, 30, 48, 51, 54, 72, 75, 78, 96, 96.5, 97, 98, 100, 102, 108, 120, 144, and 168 hours after the first dose. Blood rapamycin concentration was determined by a validated liquid chromatography-tandem mass spectrometry assay. Pharmacokinetic parameters were determined by compartmental and non-compartmental analyses. Results Mean ± SD blood rapamycin terminal half-life, area under the concentration-time curve from 0 to 48 hours after dosing, and maximum concentration were 38.7 ± 12.7 h, 140 ± 23.9 ng•h/mL, and 8.39 ± 1.73 ng/mL, respectively, for experiment 1, and 99.5 ± 89.5 h, 126 ± 27.1 ng•h/mL, and 5.49 ± 1.99 ng/mL, respectively, for experiment 2. Pharmacokinetic parameters for rapamycin after administration of 5 daily doses differed significantly from those after administration of 1 dose. Conclusions and Clinical Relevance Results indicated that oral administration of low-dose (0.1 mg/kg) rapamycin to healthy dogs achieved blood concentrations measured in ng/mL. The optimal dose and administration frequency of rapamcyin required to achieve therapeutic effects in tumor-bearing dogs, as well as toxicity after chronic dosing, needs to be determined. PMID:26709938

  20. Fluralaner as a single dose oral treatment for Caparinia tripilis in a pygmy African hedgehog.

    Science.gov (United States)

    Romero, Camilo; Sheinberg Waisburd, Galia; Pineda, Jocelyn; Heredia, Rafael; Yarto, Enrique; Cordero, Alberto M

    2017-12-01

    African pygmy hedgehogs (Atelerix albiventris) are popular pets belonging to the Erinaceidae family of spined mammals. Amongst the most common skin diseases occurring in this species is infestation caused by the mite Caparinia spp. Due to their skin anatomy and spiny coat, detection of skin lesions in these hedgehogs can be difficult. This may result in delays in seeking medical care, which may lead to secondary bacterial infection and self-inflicted trauma. Multiple therapies have been used in the treatment of this skin condition including ivermectin, amitraz, fipronil and selamectin. A drug which could be administered as a single oral dose would be advantageous to these pets and their owners. To evaluate the effect of a single oral dose (15 mg/kg) of fluralaner on Caparinia tripilis infestation in the African pygmy hedgehog. A 10-month-old African pygmy hedgehog weighing 184 g. Response to treatment was monitored by dermatological examination and superficial skin scrapings repeated at 7, 14, 21, 30, 60, 90 and 120 days following fluralaner administration. On Day 7 after treatment, adult mites were observed exhibiting normal movement. On Day 14, only dead mites were observed. No life stages of the mites were found after Day 21. A single oral dose at 15 mg/kg of fluralaner was effective within 21 days after treatment for capariniasis in this case. Further studies are required to evaluate the drug's safety and toxicology in hedgehogs, and to confirm efficacy. © 2017 ESVD and ACVD.

  1. Pan-oral dose assessment: a comparative report of methodologies

    International Nuclear Information System (INIS)

    Shafford, J.; Pryor, M.; Hollaway, P.; Peet, D.; Oduko, J.

    2015-01-01

    National guidance from the Institute of Physics and Engineering in Medicine (IPEM Report 91) currently recommends that the patient dose for a pan-oral X-ray unit is measured as dose area product (DAP) replacing dose width product described in earlier guidance. An investigation identifying different methods available to carry out this measurement has been undertaken and errors in the methodologies analysed. It has been shown that there may be up to a 30 % variation in DAP measurement between methods. This paper recommends that where possible a DAP meter is used to measure the dose-area product from a pan-oral X-ray unit to give a direct DAP measurement. However, by using a solid-state dose measurement and film/ruler to calculate DAP the authors have established a conversion factor of 1.4. It is strongly recommended that wherever a DAP value is quoted the methodology used to obtain that value is also reported. (authors)

  2. Oral repeated-dose systemic and reproductive toxicity of 6:2 fluorotelomer alcohol in mice

    Directory of Open Access Journals (Sweden)

    Pushkor Mukerji

    2015-01-01

    Full Text Available 6:2 fluorotelomer alcohol (6:2 FTOH was evaluated for potential systemic repeated-dose and reproductive toxicity in mice. 6:2 FTOH was administered by oral gavage to CD-1 mice as a suspension in 0.5% aqueous methylcellulose with 0.1% Tween-80 at dosages of 1, 5, 25, or 100 mg/kg/day. The no-observed-adverse-effect level (NOAEL for systemic toxicity was 25 mg/kg/day (males and 5 mg/kg/day (females, based on effects at higher doses on mortality, clinical observations, body weight, nutritional parameters, hematology (red and white blood cell, clinical chemistry (liver-related, liver weights, and histopathology (liver, teeth, reproductive tract, and mammary gland. However, 6:2 FTOH was not a selective reproductive toxicant. The NOAEL for reproductive toxicity was >100 mg/kg/day; no effects on reproductive outcome were observed at any dosage. The NOAEL for viability and growth of the offspring was 25 mg/kg/day, based on clinical signs of delayed maturation in pups, and reductions in pup survival and pup body weight during lactation at 100 mg/kg/day. While the severity of the effects was generally greater in mice than previously reported in CD rats, the overall NOAELs were identical in both species, 5 mg/kg/day for systemic toxicity and 25 mg/kg/day for offspring viability/growth. 6:2 FTOH was not a selective reproductive toxicant in either species; no effects on reproductive outcome occurred at any dose level, and any effects observed in offspring occurred at dose levels that induced mortality and severe toxicity in maternal animals.

  3. Concentrations of amoxicillin and clindamycin in teeth following a single dose of oral medication.

    Science.gov (United States)

    Schüssl, Yvonne; Pelz, Klaus; Kempf, Jürgen; Otten, Jörg-Elard

    2014-01-01

    The main purpose of this study is the detection of amoxicillin and clindamycin concentrations in teeth. Eleven patients received 2 g of amoxicillin, and 11 patients received 600 mg of clindamycin in a single dose of oral medication at least 60 min prior to tooth extraction due to systemic diseases. The concentrations were determined in crowns and roots separately using liquid chromatography-tandem mass spectrometry (LC-MS-MS). Amoxicillin (13 samples) and clindamycin (12 samples) were detected in the samples of the root and crown preparations of the extracted teeth. The mean concentration of amoxicillin was 0.502 μg/g in the roots and 0.171 μg/g in the crowns. The mean concentration of clindamycin was 0.270 μg/g in the roots and 0.064 μg/g in the crowns. A single dose of oral amoxicillin and clindamycin leads to concentrations of both antibiotics in teeth which exceed the minimal inhibition concentration of some oral bacteria. The proof of antibacterial activity in dental hard tissue after oral single-dose application is new. The antimicrobial effect of amoxicillin and clindamycin concentrations in roots of teeth may be of clinical relevance to bacterial reinfection from dentinal tubules.

  4. Equivalence of a single dose (1200 mg) compared to a three-time a day dose (400 mg) of chondroitin 4&6 sulfate in patients with knee osteoarthritis. Results of a randomized double blind placebo controlled study.

    Science.gov (United States)

    Zegels, B; Crozes, P; Uebelhart, D; Bruyère, O; Reginster, J Y

    2013-01-01

    Evaluation of the efficacy and safety of a single oral dose of a 1200 mg sachet of chondroitin 4&6 sulfate (CS 1200) vs three daily capsules of chondroitin 4&6 sulfate 400 mg (CS 3*400) (equivalence study) and vs placebo (superiority study) during 3 months, in patients with knee osteoarthritis (OA). Comparative, double-blind, randomized, multicenter study, including 353 patients of both genders over 45 years with knee OA. Minimum inclusion criteria were a Lequesne index (LI) ≥ 7 and pain ≥ 40 mm on a visual analogue scale (VAS). LI and VAS were assessed at baseline and after 1-3 months. Equivalence between CS was tested using the per-protocol procedure and superiority of CS vs placebo was tested using an intent-to-treat procedure. After 3 months of follow-up, no significant difference was demonstrated between the oral daily single dose of CS 1200 formulation and the three daily capsules of CS 400. Patients treated with CS 1200 or CS 3*400 were significantly improved compared to placebo after 3 months of follow-up in terms of LI (security and tolerability was observed between the three groups. This study suggests that a daily administration of an oral sachet of 1200 mg of chondroitin 4&6 sulfate allows a significant clinical improvement compared to a placebo, and a similar improvement when compared to a regimen of three daily capsules of 400 mg of the same active ingredient. Copyright © 2012 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  5. Effects of low dose aspirin (50 mg/day), low dose aspirin plus dipyridamole, and oral anticoagulant agents after internal mammary artery bypass grafting: patency and clinical outcome at 1 year. CABADAS Research Group of the Interuniversity Cardiology Institute of The Netherlands. Prevention of Coronary Artery Bypass Graft Occlusion by Aspirin, Dipyridamole and Acenocoumarol/Phenprocoumon Study

    NARCIS (Netherlands)

    van der Meer, J.; Brutel de la Rivière, A.; van Gilst, W. H.; Hillege, H. L.; Pfisterer, M.; Kootstra, G. J.; Dunselman, P. H.; Mulder, B. J.; Lie, K. I.

    1994-01-01

    This study was performed to compare the efficacy and safety of aspirin, aspirin plus dipyridamole, and oral anticoagulant agents in the prevention of internal mammary artery graft occlusion. Antithrombotic drugs increase vein graft patency after coronary artery bypass surgery. Their benefit after

  6. Single dose oral ibuprofen plus paracetamol (acetaminophen) for acute postoperative pain.

    Science.gov (United States)

    Derry, Christopher J; Derry, Sheena; Moore, R Andrew

    2013-06-24

    Combining two different analgesics in fixed doses in a single tablet can provide better pain relief than either drug alone in acute pain. This appears to be broadly true across a range of different drug combinations, in postoperative pain and migraine headache. Some combinations of ibuprofen and paracetamol are available for use without prescription in some acute pain situations. To assess the efficacy and adverse effects of single dose oral ibuprofen plus paracetamol for acute postoperative pain using methods that permit comparison with other analgesics evaluated in standardised trials using almost identical methods and outcomes. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library (Issue 4 of 12, 2013), MEDLINE (1950 to May 21st 2013), EMBASE (1974 to May 21st 2013), the Oxford Pain Database, ClinicalTrials.gov, and reference lists of articles. Randomised, double-blind clinical trials of single dose, oral ibuprofen plus paracetamol compared with placebo or the same dose of ibuprofen alone for acute postoperative pain in adults. Two review authors independently considered trials for inclusion in the review, assessed quality, and extracted data. We used validated equations to calculate the area under the pain relief versus time curve and derive the proportion of participants with at least 50% of maximum pain relief over six hours. We calculated relative risk (RR) and number needed to treat to benefit (NNT) for ibuprofen plus paracetamol, ibuprofen alone, or placebo. We used information on use of rescue medication to calculate the proportion of participants requiring rescue medication and the weighted mean of the median time to use. We also collected information on adverse events. Searches identified three studies involving 1647 participants. Each of them examined several dose combinations. Included studies provided data from 508 participants for the comparison of ibuprofen 200 mg + paracetamol 500 mg with placebo, 543

  7. Pharmacokinetics of voriconazole after oral administration of single and multiple doses in Hispaniolan Amazon parrots (Amazona ventralis).

    Science.gov (United States)

    Sanchez-Migallon Guzman, David; Flammer, Keven; Papich, Mark G; Grooters, Amy M; Shaw, Shannon; Applegate, Jeff; Tully, Thomas N

    2010-04-01

    To determine the pharmacokinetics and safety of voriconazole administered orally in single and multiple doses in Hispaniolan Amazon parrots (Amazona ventralis). 15 clinically normal adult Hispaniolan Amazon parrots. Single doses of voriconazole (12 or 24 mg/kg) were administered orally to 15 and 12 birds, respectively; plasma voriconazole concentrations were determined at intervals via high-pressure liquid chromatography. In a multiple-dose trial, voriconazole (18 mg/kg) or water was administered orally to 6 and 4 birds, respectively, every 8 hours for 11 days (beginning day 0); trough plasma voriconazole concentrations were evaluated on 3 days. Birds were monitored daily, and clinicopathologic variables were evaluated before and after the trial. Voriconazole elimination half-life was short (0.70 to 1.25 hours). In the single-dose experiments, higher drug doses yielded proportional increases in the maximum plasma voriconazole concentration (C(max)) and area under the curve (AUC). In the multiple-dose trial, C(max), AUC, and plasma concentrations at 2 and 4 hours were decreased on day 10, compared with day 0 values; however, there was relatively little change in terminal half-life. With the exception of 1 voriconazole-treated parrot that developed polyuria, adverse effects were not evident. In Hispaniolan Amazon parrots, oral administration of voriconazole was associated with proportional kinetics following administration of single doses and a decrease in plasma concentration following administration of multiple doses. Oral administration of 18 mg of voriconazole/kg every 8 hours would require adjustment to maintain therapeutic concentrations during long-term treatment. Safety and efficacy of voriconazole treatment in this species require further investigation.

  8. Single Oral Dose Toxicity Test of Blue Honeysuckle Concentrate in Mice

    Science.gov (United States)

    Park, Sang-In; Choi, Seung-Hoon; Song, Chang-Hyun; Park, Soo-Jin; Shin, Yong-Kook; Han, Chang-Hyun; Lee, Young Joon; Ku, Sae-Kwang

    2015-01-01

    The objective of this study was to obtain single oral dose toxicity information for concentrated and lyophilized powder of blue honeysuckle (Lonicera caerulea L., Caprifoliaceae; BHcL) in female and male ICR mice to aid in the process of developing natural origin medicinal ingredients or foods following proximate analysis and phytochemical profile measurement. The proximate analysis revealed that BHcL had an energy value of 3.80 kcal/g and contained 0.93 g/g of carbohydrate, 0.41 g/g of sugar, 0.02 g/g of protein, and 0.20 mg/g of sodium. BHcL did not contain lipids, including saturated lipids, trans fats, or cholesterols. Further, BHcL contained 4.54% of betaine, 210.63 mg/g of total phenols, 159.30 mg/g of total flavonoids, and 133.57 mg/g of total anthocyanins. Following administration of a single oral BHcL treatment, there were no treatment-related mortalities, changes in body weight (bw) or organ weight, clinical signs, necropsy or histopathological findings up to 2,000 mg/kg bw, the limited dosage for rodents of both sexes. We concluded that BHcL is a practically non-toxic material in toxicity potency. PMID:25874034

  9. Single dose (400 mg) versus 7 day (200 mg) daily dose itraconazole in the treatment of tinea versicolor: a randomized clinical trial.

    Science.gov (United States)

    Wahab, M A; Ali, M E; Rahman, M H; Chowdhury, S A; Monamie, N S; Sultana, N; Khondoker, L

    2010-01-01

    Tinea (pityriasis) versicolor is a superficial fungal infection and one of the most commonly found pigmentary disorders of skin caused by the yeast Malassezia. Multiple topical as well as systemic therapies are available for treatment. Systemic therapies are used for extensive disease, frequent relapse or where topical agents have failed. The aim that translates the rationale of the study was to compare the efficacy, safety, tolerability and cost effectiveness of single dose 400mg versus 7 day 200 mg daily dose of itraconazole in the treatment of tinea versicolor. A clinical study was done to compare the efficacy of single dose (400 mg) of itraconazole and 7 day 200 mg daily dose of itraconazole in the treatment of extensive tinea versicolor. Total 60 patients (aged 18-50 years) were selected for the study during the period of June 2007 to May 2008 in the department of Dermatology of three different hospitals in Bangladesh. Cases having with extensive involvement, diagnosed clinically and confirmed by wood's lamp and KOH microscopy were taken. Patients were randomly allocated into equal groups. Group A was given single dose 400 mg itraconazole and Group B was given 7 day 200 mg daily itraconazole. Fifty three (88%) male and 7(12%) female were included in the study. The mean age of group A was 32.37+/-9 years and in group B 33.23+/-8 years. The mean duration of the disease in group A was 2.63+/-2 months and 2.76+/-2 months in group B. In group A clinical responders was found cure 22(73.33%) and improvement 5(16.33%) and in group B it was found cure 24(79.99%) and improvement 4(13.33%). The measure at the End point (EP1) equals to 90% response and in-group B it was found cure 24 (79.99%) and improvement 4(13.33%). (Here the End point EP2) equals to 93.33%. The EP clinical analysis however shows 91.66% response. Both single dose and 7 day daily dose of itraconazole can be effective in the treatment of tinea versicolor with extensive involvement but single dose appears

  10. Low-dose intranasal versus oral midazolam for routine body MRI of claustrophobic patients

    Energy Technology Data Exchange (ETDEWEB)

    Tschirch, Frank T.C.; Goepfert, Kerstin; Brunner, Genevieve; Weishaupt, Dominik [University Hospital Zuerich, Institute of Diagnostic Radiology, Zuerich (Switzerland); Froehlich, Johannes M. [Klus-Apotheke, Zuerich (Switzerland)

    2007-06-15

    The purpose of this study was to assess prospectively the potential of low-dose intranasal midazolam compared to oral midazolam in claustrophobic patients undergoing routine body magnetic resonance imaging (MRI). Seventy-two adult claustrophobic patients referred for body MRI were randomly assigned to one of two treatment groups (TG1 and TG2). The 36 patients of TG1 received 7.5 mg midazolam orally 15 min before MRI, whereas the 36 patients of TG2 received one (or, if necessary, two) pumps of a midazolam nasal spray into each nostril immediately prior to MRI (in total, 1 or 2 mg). Patients' tolerance, anxiety and sedation were assessed using a questionnaire and a visual analogue scale immediately before and after MRI. Image quality was evaluated using a five-point-scale. In TG1, 18/36 MRI examinations (50%) had to be cancelled, the reduction of anxiety was insufficient in 12/18 remaining patients (67%). In TG2, 35/36 MRI examinations (97%) were completed successfully, without relevant adverse effects. MRI image quality was rated higher among patients of TG2 compared to TG1 (p<0.001). Low-dose intranasal midazolam is an effective and patient-friendly solution to overcome anxiety in claustrophobic patients in a broad spectrum of body MRI. Its anxiolytic effect is superior to that of the orally administrated form. (orig.)

  11. Frequency and severity of reactions to a 325-mg aspirin dose during desensitization.

    Science.gov (United States)

    Schuler, Charles F; Baldwin, James L; Baptist, Alan P

    2017-03-01

    The frequency with which patients with aspirin-exacerbated respiratory disease (AERD) react to 325 mg of aspirin during aspirin desensitization, or fail to react at all, is not fully known. To determine the rate and type of reaction at 325 mg of aspirin during desensitization. A retrospective study of 104 patients who underwent aspirin desensitization from 2010 to 2016 was performed. A standard desensitization protocol (starting at 20-40 mg, progressing through 325 mg, and extinguishing reactions by dose repetition) was used. Reactions were defined by upper respiratory tract symptoms, lower respiratory tract symptoms, and/or forced expiratory volume in 1 second decrease of 15% or greater. Patients who did and did not react were compared by logistic regression. Eighty-four patients reacted (81%) and 20 did not (19%). Seventy-seven patients who had a provoking reaction at 162 mg of aspirin or less subsequently extinguished their reactions before they reached a dose of 325 mg and had no problems at that dose; one subsequent 325-mg reaction occurred during a protocol violation. One initial provoking reaction to 325 mg occurred. Both 325-mg reactions were mild, and neither met the forced expiratory volume in 1 second criterion for a clinically meaningful change. The remaining 5 patients could not complete the protocol because of persistent reactions or social reasons. Reactors were more likely to have had asthma for more than 10 years than nonreactors (odds ratio, 3.2; 95% confidence interval, 1.0-10.3; P = .05). During aspirin desensitization for AERD, provoking reactions at the 325-mg dose are rare (1%) and mild. Patients who react at 162 mg or less and extinguish their reactions may be able to administer the 325-mg dose at home. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  12. Randomized clinical trial comparing oral prednisone (50 mg) with placebo before laparoscopic cholecystectomy

    DEFF Research Database (Denmark)

    Bisgaard, Thue; Schulze, S.; Hjortso, N.C.

    2008-01-01

    cholecystectomy. Methods In a double-blind placebo-controlled study, 200 patients were randomized to oral administration of prednisone (50 mg) or placebo 2 h before laparoscopic cholecystectomy. Patients received a similar standardized anaesthetic, surgical, and analgesic treatment. The primary outcome was pain......-h pain, fatigue or malaise scores or any other variables were found (P > 0.05). Conclusion There is no important clinical gain of preoperative oral steroid administration compared with placebo in patients undergoing laparoscopic cholecystectomy Udgivelsesdato: 2008/2...

  13. The dose effects of short-term dronabinol (oral THC) maintenance in daily cannabis users.

    Science.gov (United States)

    Vandrey, Ryan; Stitzer, Maxine L; Mintzer, Miriam Z; Huestis, Marilyn A; Murray, Jeannie A; Lee, Dayong

    2013-02-01

    Prior studies have separately examined the effects of dronabinol (oral THC) on cannabis withdrawal, cognitive performance, and the acute effects of smoked cannabis. A single study examining these clinically relevant domains would benefit the continued evaluation of dronabinol as a potential medication for the treatment of cannabis use disorders. Thirteen daily cannabis smokers completed a within-subject crossover study and received 0, 30, 60 and 120mg dronabinol per day for 5 consecutive days. Vital signs and subjective ratings of cannabis withdrawal, craving and sleep were obtained daily; outcomes under active dose conditions were compared to those obtained under placebo dosing. On the 5th day of medication maintenance, participants completed a comprehensive cognitive performance battery and then smoked five puffs of cannabis for subjective effects evaluation. Each dronabinol maintenance period occurred in a counterbalanced order and was separated by 9 days of ad libitum cannabis use. Dronabinol dose-dependently attenuated cannabis withdrawal and resulted in few adverse side effects or decrements in cognitive performance. Surprisingly, dronabinol did not alter the subjective effects of smoked cannabis, but cannabis-induced increases in heart rate were attenuated by the 60 and 120mg doses. Dronabinol's ability to dose-dependently suppress cannabis withdrawal may be therapeutically beneficial to individuals trying to stop cannabis use. The absence of gross cognitive impairment or side effects in this study supports safety of doses up to 120mg/day. Continued evaluation of dronabinol in targeted clinical studies of cannabis treatment, using an expanded range of doses, is warranted. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  14. New approach for food allergy management using low-dose oral food challenges and low-dose oral immunotherapies.

    Science.gov (United States)

    Yanagida, Noriyuki; Okada, Yu; Sato, Sakura; Ebisawa, Motohiro

    2016-04-01

    A number of studies have suggested that a large subset of children (approximately 70%) who react to unheated milk or egg can tolerate extensively heated forms of these foods. A diet that includes baked milk or egg is well tolerated and appears to accelerate the development of regular milk or egg tolerance when compared with strict avoidance. However, the indications for an oral food challenge (OFC) using baked products are limited for patients with high specific IgE values or large skin prick test diameters. Oral immunotherapies (OITs) are becoming increasingly popular for the management of food allergies. However, the reported efficacy of OIT is not satisfactory, given the high frequency of symptoms and requirement for long-term therapy. With food allergies, removing the need to eliminate a food that could be consumed in low doses could significantly improve quality of life. This review discusses the importance of an OFC and OIT that use low doses of causative foods as the target volumes. Utilizing an OFC or OIT with a low dose as the target volume could be a novel approach for accelerating the tolerance to causative foods. Copyright © 2015 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

  15. A chewable low-dose oral contraceptive: a new birth control option?

    Directory of Open Access Journals (Sweden)

    Weisberg E

    2012-04-01

    Full Text Available Edith Weisberg1,21Sydney Centre for Reproductive Health Research, Research Division of Family Planning NSW, 2Department of Obstetrics and Gynaecology, Queen Elizabeth II Research Institute for Mothers and Infants, University of Sydney, Sydney, AustraliaAbstract: A new chewable combined oral contraceptive pill containing ethinyl estradiol (EE 0.025 mg and norethindrone (NE 0.8 mg in a 24/4 regimen was approved for marketing in December 2010. Each of the four inactive tablets contains 75 mg ferrous fumarate, which has no therapeutic benefit. The tablet can be taken with food but not water as this affects the absorption of EE. The Pearl index based on intention to treat women aged 18–35 years has been reported at 2.01 (confidence interval [CI] 1.21, 3.14 and for the whole population 1.65 (CI 1.01, 2.55. The effect of a body mass index of >35 was not studied. Regular withdrawal bleeding occurred for 78.6% of women in Cycle 1, but by Cycle 13 almost half the women failed to have a withdrawal bleed. This new formulation provides an intermediate dose of an EE/NE combination that will be useful for women experiencing breakthrough bleeding on the lower-dose EE/NE pill. The convenience of a low-dose pill, which can be chewed without the need for water, will be useful to enable women who have forgotten a pill to take one whenever they remember, provided they carry it with them. The advantage of a 24/4 regimen is better suppression of follicular development in the pill-free interval and may be beneficial for women who experience menstrual cycle-related problems, such as heavy bleeding or dysmenorrhea.Keywords: combined oral contraceptive, low dose, ethinyl estradiol, norethindrone

  16. Stability of a1 mg/mL oral solution zidovudine

    International Nuclear Information System (INIS)

    Garcia Penna, Caridad Margarita; Morales Lacarrere, Ivan; Martinez Espinosa, Vivian

    2011-01-01

    The carrying out of a high-performance liquid chromatography analytical method was assessed; applicable to stability study of oral solution zidovudine (1 mg/mL) was made. The analytical method was linear, precise, specific and exact in the study concentrations. The stability study of oral solution zidovudine (1 mg/mL) was conducted determining expiring date. The shelf life study was conducted over 24 months at room temperature; whereas that of accelerated stability was conducted with the product under wet and temperature conditions; analysis was carried out over three months. Formula met quality specifications described in Pharmacopeia. Results from the shelf life study demonstrated that product keeps the parameters determining its quality during that time and in accelerated studies there was not significant product degradation. Under above mentioned conditions two years were established as expiring date

  17. Oral exposure to low-dose of nonylphenol impairs memory performance in Sprague-Dawley rats.

    Science.gov (United States)

    Kawaguchi, Shinichiro; Kuwahara, Rika; Kohara, Yumi; Uchida, Yutaro; Oku, Yushi; Yamashita, Kimihiro

    2015-02-01

    Nonylphenol ethoxylate (NPE) is a non-ionic surfactant, that is degraded to short-chain NPE and 4-nonylphenol (NP) by bacteria in the environment. NP, one of the most common environmental endocrine disruptors, exhibits weak estrogen-like activity. In this study, we investigated whether oral administration of NP (at 0.5 and 5 mg/kg doses) affects spatial learning and memory, general activity, emotionality, and fear-motivated learning and memory in male and female Sprague-Dawley (SD) rats. SD rats of both sexes were evaluated using a battery of behavioral tests, including an appetite-motivated maze test (MAZE test) that was used to assess spatial learning and memory. In the MAZE test, the time required to reach the reward in male rats treated with 0.5 mg/kg NP group and female rats administered 5 mg/kg NP was significantly longer than that for control animals of the corresponding sex. In other behavioral tests, no significant differences were observed between the control group and either of the NP-treated groups of male rats. In female rats, inner and ambulation values for animals administered 0.5 mg/kg NP were significantly higher than those measured in control animals in open-field test, while the latency in the group treated with 5 mg/kg NP was significantly shorter compared to the control group in step-through passive avoidance test. This study indicates that oral administration of a low-dose of NP slightly impairs spatial learning and memory performance in male and female rats, and alters emotionality and fear-motivated learning and memory in female rats only.

  18. Study of the response reduction of LiF:Mg, Ti dosimeter for high dose dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    Torkzadeh, Falamarz [Nuclear Sciences and Technology Research Institute, Tehran (Iran, Islamic Republic of). Radiation Applications Research School; AEOI, Tehran (Iran, Islamic Republic of); Faripour, Heidar [Nuclear Sciences and Technology Research Institute, Tehran (Iran, Islamic Republic of). Laser and Optics Research School; AEOI, Tehran (Iran, Islamic Republic of); Mardashti, Forough; Manouchehri, Farhad [Nuclear Sciences and Technology Research Institute, Tehran (Iran, Islamic Republic of). Radiation Applications Research School

    2017-07-15

    A single crystal and 5 polycrystalline samples of LiF:Mg, Ti and their pellets were prepared and investigated so as to apply thermoluminescence high gamma dose dosimetry. Three zones of single crystal with dopant concentrations of 200 ppm of Mg and 20 ppm of Ti were also used to prepare the single crystal samples. For polycrystalline samples, dopant concentrations of 0.062 mol% Mg and Ti concentrations in the range of 0.016 and 0.046 mol% were used. All the samples were exposed to gamma doses of 1 kGy to 700 kGy and their response changes were determined by a gamma dose test of about 60 mGy. According to the results obtained, the use of response reduction by curve-fitting up to about 300 kGy can be performed reliably for high dose gamma dosimetry.

  19. nduced hyperlipidemic rats. Methods: Column chromatographic fractionation of butanol fraction of total methanol extract of leaves of Bauhinia variegata (Linn. yields four sub-fractions (sub-fraction A-D. All sub-fractions tested for their anti-hyperlipidemic activity. Sub-fractions administered at a dose of 65 mg/kg (oral to the Triton WR-1339 induced hyperlipidemic rats and total cholesterol, triglycerides, HDL, LDL and VLDL

    Directory of Open Access Journals (Sweden)

    Deepak Kumar

    2012-10-01

    Full Text Available Objective: To investigate the effect and evaluation of Anti-hyperlipidemic activity guided subfraction isolated from total methanolic extract of Bauhinia variegata (Linn. leaves on Triton WR-1339 induced hyperlipidemic rats. Methods: Column chromatographic fractionation of butanol fraction of total methanol extract of leaves of Bauhinia variegata (Linn. yields four subfractions (sub-fraction A-D. All sub-fractions tested for their anti-hyperlipidemic activity. Subfractions administered at a dose of 65 mg/kg (oral to the Triton WR-1339 induced hyperlipidemic rats and total cholesterol, triglycerides, HDL, LDL and VLDL level in the blood were checked. Results: Sub-fraction D showed significant reduction (P<0.05 among four sub-fraction in comparison with standard drug fenofibrate. Conclusions: From the above study it could be concluded that butanol sub-fraction D of Bauhinia variegata (Linn. not only have resulted in significant reduction in cholesterol, triglyceride, LDL, VLDL level but also increases the HDL level at a reduced dose level.

  20. High Dose Oral Calcium Treatment in Patients with Vitamin D-dependent Rickets Type II

    Directory of Open Access Journals (Sweden)

    R Vakili

    2017-02-01

    Full Text Available BACKGROUND AND OBJECTIVE: Vitamin D-dependent rickets type II (VDDR2 is a rare genetic disorder caused by mutations in vitamin D receptor (VDR and leads to resistance to biological effects of calcitriol. Based on the type of mutation, this disease is resistant to calcitriol even at high doses of calcitriol and successful treatment of these patients requires hypocalcemic modification through administration of high doses of calcium and bypassing the intestinal defect in VDR signaling. In addition to the need for frequent hospitalization and high costs, intravenous administration of calcium is associated with complications and problems such as arrhythmia and sepsis, venous catheter infection and hypercalciuria. This study aims to report the positive treatment effects of high doses of oral calcium in 4 patients with vitamin D-dependent rickets type II. CASE REPORT: In this study, 4 patients with vitamin D-dependent rickets type II, diagnosed based on clinical and biochemical symptoms of rickets with alopecia, underwent therapy using high doses of oral calcium (300 mg/kg/day in pediatric endocrinology and metabolism center of Imam Reza hospital. After a short period, increased growth rate in height, strength and elasticity of muscles was observed in addition to biochemical improvements without serious side effects and even one patient started walking independently within the first week of therapy for the first time. Patients were regularly followed up in terms of height and weight, growth rate and biochemical factors including calcium, phosphorus and alkaline phosphatase every 3 months for one year. CONCLUSION: Regardless of the type of mutation in vitamin D receptor, it is suggested that a 3-6 months trial of high dose oral calcium be started in each patient with vitamin D-dependent rickets type II, particularly for patients whose disease was diagnosed at lower ages.

  1. Lack of dose dependent kinetics of methyl salicylate-2-O-β-D-lactoside in rhesus monkeys after oral administration.

    Science.gov (United States)

    He, Yangyang; Yan, Yu; Zhang, Tiantai; Ma, Yinzhong; Zhang, Wen; Wu, Ping; Song, Junke; Wang, Shuang; Du, Guanhua

    2015-04-22

    Methyl salicylate-2-O-β-d-lactoside (MSL) is one of the main active components isolated from Gaultheria yunnanensis, which is a traditional Chinese medicine used to treat arthritis and various aches and pains. Pharmacological researches showed that MSL had various effective activities in both in vivo and in vitro experiments. However, the pharmacokinetics features and oral bioavailability of MSL in primates were not studied up to now. To study the pharmacokinetics of different doses of MSL in rhesus monkeys and investigate the absolute bioavailability of MSL after oral administration. Male and female rhesus monkeys were either orally administrated with MSL 200, 400 and 800 mg/kg or received an intravenous dose of 20mg/kg randomly. The levels of MSL and salicylic acid (SA) in plasma were simultaneous measured by a simple, sensitive and reproducible high performance liquid chromatography method. Mean peak plasma concentration values for groups treated with 200, 400 and 800 mg/kg doses ranged from 48.79 to 171.83 μg/mL after single-dose oral administration of MSL, and mean area under the concentration-time curve values ranged from 195.16 to 1107.76 μg/mL h. Poor linearity of the kinetics of SA after oral administration of MSL was observed in the regression analysis of the Cmax-dose plot (r(2)=0.812), CL-dose plot (r(2)=0.225) and AUC(0-t)-dose plot (r(2)=0.938). Absolute bioavailability of MSL was assessed to be 118.89 ± 57.50, 213.54 ± 58.98 and 168.72 ± 76.58%, respectively. Bioavailability of MSL after oral administration in rhesus monkeys was measured for the first time. Pharmacokinetics parameters did not appear to be dose proportional among the three oral doses of treatments, and MSL showed an apparent absolute bioavailability in excess of 100% in rhesus monkeys based on the present study. In addition, a rapid, sensitive and reliable HPLC method was established and demonstrated for the research of traditional Chinese medicine in this study. Copyright

  2. Comparative pharmacokinetics of oxytetracycline in blunt-snout bream (Megalobrama amblycephala) with single and multiple-dose oral administration.

    Science.gov (United States)

    Li, Ru-Qin; Ren, Yu-Wei; Li, Jing; Huang, Can; Shao, Jun-Hui; Chen, Xiao-Xuan; Wu, Zhi-Xin

    2015-06-01

    Research into the pharmacokinetics and residue elimination of oxytetracycline (OTC) is important both to determine the optimal dosage regimens and to establish a safe withdrawal time in fish. A depletion study is presented here for OTC in Megalobrama amblycephala with a single-dose (100 mg/kg) and multiple-dose (100 mg/kg for five consecutive days) oral administration. The study was conducted at 25 °C. As a result, a one-compartment model was developed. For the single dose, the absorption half-life was 5.79, 9.40, 6.96, and 8.06 h in the plasma, liver, kidney, and muscle, respectively. However, the absorption half-life was 3.62, 7.33, 4.59, and 6.02 h with multiple-dose oral administration. The elimination half-time in the plasma, liver, kidney, and muscle was 58.63, 126.43, 65.1, and 58.85 h when M. amblycephala was treated with a single dose. However, the elimination half-time changed to 91.75, 214.87, 126.22, and 135.84 h with multiple-dose oral administration.

  3. Brachytherapy for early oral tongue cancer. Low dose rate to high dose rate

    International Nuclear Information System (INIS)

    Yamazaki, Hideya; Inoue, Takehiro; Yoshida, Ken; Yoshioka, Yasuo; Shimizutani, Kimishige; Inoue, Toshihiko; Furukawa, Souhei; Kakimoto, Naoya

    2003-01-01

    To examine the compatibility of low dose rate (LDR) with high dose rate (HDR) brachytherapy, we reviewed 399 patients with early oral tongue cancer (T1-2N0M0) treated solely by brachytherapy at Osaka University Hospital between 1967 and 1999. For patients in the LDR group (n=341), the treatment sources consisted of Ir-192 pin for 227 patients (1973-1996; irradiated dose, 61-85 Gy; median, 70 Gy), Ra-226 needle for 113 patients (1967-1986; 55-93 Gy; median, 70 Gy). Ra-226 and Ir-192 were combined for one patient. Ir-192 HDR (microSelectron-HDR) was used for 58 patients in the HDR group (1991-present; 48-60 Gy; median, 60 Gy). LDR implantations were performed via oral and HDR via a submental/submandibular approach. The dose rates at the reference point for the LDR group were 0.30 to 0.8 Gy/h, and for the HDR group 1.0 to 3.4 Gy/min. The patients in the HDR group received a total dose of 48-60 Gy (8-10 fractions) during one week. Two fractions were administered per day (at least a 6-h interval). The 3- and 5-year local control rates for patients in the LDR group were 85% and 80%, respectively, and those in the HDR group were both 84%. HDR brachytherapy showed the same lymph-node control rate as did LDR brachytherapy (67% at 5 years). HDR brachytherapy achieved the same locoregional result as did LDR brachytherapy. A converting factor of 0.86 is applicable for HDR in the treatment of early oral tongue cancer. (author)

  4. Successful treatment for subinvolution of placental sites in the bitch with low oral doses of progestagen.

    Science.gov (United States)

    Voorhorst, M J; van Brederode, J C; Albers-Wolthers, C H J; de Gier, J; Schaefers-Okkens, A C

    2013-10-01

    Subinvolution of placental sites (SIPS) is the major cause of persistent sanguineous vaginal discharge after parturition in the bitch. Spontaneous remission is common but may take several months, and hence, medical therapy to end the discharge is often requested. In this retrospective study, we evaluated the effect of treatment for SIPS with low oral doses of a progestagen. Nine bitches with SIPS, but otherwise clinically healthy, were found in the computer database of the Department of Clinical Sciences of Companion Animals. Seven of these bitches were treated with low oral doses of a progestagen (megestrol acetate, 0.1 mg/kg body weight (bw) once daily for the 1st week, then 0.05 mg/kg bw once daily for the 2nd week). The other two bitches were untreated. Treatment results were evaluated by a telephone questionnaire. Progestagen treatment was successful in all of the treated dogs; sanguineous vaginal discharge stopped within the treatment period. One of the two untreated dogs remained symptomatic until the next oestrus, approximately 120 days after parturition, and the other remained symptomatic until 6 weeks before the start of the next pro-oestrus, 270 days after parturition. No side effects of the progestagen treatment were observed. Subsequent gestations, parturitions and puerperal periods of 5 mated bitches were uneventful. One bitch did not become pregnant after mating. In conclusion, the results of this study indicate that oral administration of low doses of progestagen for 2 weeks is effective in stopping persistent sanguineous vaginal discharge in bitches with SIPS, with neither side effects nor reduced subsequent fertility. © 2013 Blackwell Verlag GmbH.

  5. Brand versus generic dispensing trend for ciprofloxacin 500 mg, levofloxacin 500 mg, and moxifloxacin 400 mg (oral dosage forms) among pharmacies of Karachi, Pakistan.

    Science.gov (United States)

    Zehra, Fatima; Naqvi, Atta Abbas; Tasneem, Sumbul; Ahmad, Rizwan; Ahmad, Niyaz; Shamsi, Adnan Zia; Asghar, Naqiya Ali; Khan, Ghufran Ullah

    2017-01-01

    Pakistan spends 0.7% of its gross domestic product on health. The public sector health-care system provides services to 22% of population thus paving the way for a dominant private sector. Patients in Pakistan mostly pay their medical expenses directly, and 64% of the health expenditures are borne by the household. Expenditure on medicine constitutes 43% of the total household expenditure. A quantitative cross-sectional study was conducted in Karachi, Pakistan, for a month. It was aimed at gathering response from different pharmacies to understand the brand versus generic dispensing trend of ciprofloxacin 500 mg, levofloxacin 500 mg, and moxifloxacin 400 mg oral dosage forms. The study employed convenience sampling and used a survey checklist. The data gathered was entered in SPSS version 22. The mean price per tablet for ciprofloxacin brand and generic was reported at Pakistani Rupees (PKR) 48.44 and PKR 26.85, respectively. The trend for dispensing ciprofloxacin highlighted a split in the market between brand (51%) and generic (49%). For levofloxacin brand and generic, the price per tablet was reported at PKR 36.50 and PKR 36.15 respectively, and despite same price, the market was dominated by generic levofloxacin (92%). Due to a price difference between brand and generic moxifloxacin, i.e., PKR 129.44 and PKR 71.91, respectively, the market was mostly occupied by the generic form (75%). Pricing mechanism must be revisited, and the authorities should take stern actions against any illegitimate price hike. The surging burden of drug expenditure on poorer sections of the society must be addressed by the government on an urgent basis.

  6. Effect of single oral dose of tramadol on gastric secretions pH

    Directory of Open Access Journals (Sweden)

    Khan Mueen Ullah

    2015-01-01

    Full Text Available Background: Tramadol is an atypical analgesic agent. It has been shown that intramuscular or intravenous injection tramadol is able to inhibit M3 muscarinic receptors. Tramadol is able to mediate smooth muscles contraction and glandular secretions. We have evaluated the effects of single oral dose of tramadol given preoperatively on gastric juices pH in patients electively scheduled for laparoscopic cholecystectomy. Materials and Methods: Sixty adult, American Society of Anesthesiologist I and II patients scheduled for laparoscopic cholecystectomy were included in the study. Patients were randomly assigned to receive either placebo (n = 30 or oral tramadol 50 mg (n = 30. General anesthesia was induced using propofol, fentanyl and cisatracurium. After induction of anesthesia 5 ml of gastric fluid was aspirated through orogastric tube. The gastric fluid pH was measured using pH meter. Result: There was no significant difference in the pH between the groups. Gastric pH of the placebo and tramadol groups was 1.97 versus 1.98 (P = 0.092 respectively. Conclusion: Preoperatively single oral dose of tramadol was unable to elevate the desired level of gastric acid secretions pH (>2.5. This may be due to pharmacokinetic disparity between the analgesic and pH elevating properties of tramadol.

  7. Isavuconazole absorption following oral administration in healthy subjects is comparable to intravenous dosing, and is not affected by food, or drugs that alter stomach pH.

    Science.gov (United States)

    Schmitt-Hoffmann, Anne; Desai, Amit; Kowalski, Donna; Pearlman, Helene; Yamazaki, Takao; Townsend, Robert

    2016-08-01

    Two openlabel, single-dose, randomized crossover studies and one open-label, multiple-dose, parallel group study in healthy volunteers were conducted with the prodrug, isavuconazonium sulfate, to determine absolute bioavailability of the active triazole, isavuconazole (EudraCT 2007-004949-15; n = 14), and the effect of food (EudraCT 2007- 004940-63; n = 26), and pH (NCT02128893; n = 24) on the absorption of isavuconazole. Isavuconazonium sulfate 744 mg designed to deliver 400 mg of the active triazole isavuconazole was administered in the absolute bioavailability (oral or intravenous (IV) (2-hour infusion)) and food-effect studies (oral). In the pH-effect study, isavuconazonium sulfate 372 mg designed to deliver 200 mg of isavuconazole was administered orally three times daily (t.i.d.) for 2 days, followed by a single daily oral dose for 3 days, in the presence of steady state esomeprazole dosed orally at 40 mg/day. Isavuconazole was well tolerated in each study. Bioavailability: Geometric least squares mean ratios (GLSMR; oral/IV) for isavuconazole AUC∞, and Cmax were 98% (90% confidence interval (CI): 94, 101) and 78% (90% CI: 72, 85), respectively. Food-effect: GLSMR (fed/fasted) for AUC∞ and Cmax of isavuconazole in plasma were 110% (90% CI: 102, 118) and 92% (90% CI: 86, 98), respectively. Median tmax was 5 hours with food and 3 hours under fasted conditions. pH-effect: GLSMR for isavuconazole AUCtau and Cmax were 108% (90% CI: 89, 130) and 105% (90% CI: 89, 124), respectively. Orally administered isavuconazonium sulfate effectively delivers isavuconazole, as evidenced by the fact that oral isavuconazole is bioequivalent to the IV formulation. Dose adjustments are not required when switching between oral and IV formulations, regardless of food or drugs that increase gastric pH.

  8. Improvement in erection hardness and intercourse success with first dose of sildenafil citrate 100 mg

    Directory of Open Access Journals (Sweden)

    Mulhall JP

    2013-11-01

    Full Text Available John P Mulhall,1 Dana L Creanga,2 Vera J Stecher31Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA; 2Consultant to Pfizer Inc., New York, NY, USA; 3Medical Affairs, Primary Care Business Unit, Pfizer Inc., New York, NY, USAPurpose: To determine, in men with erectile dysfunction (ED, the extent of improvement in erection hardness and in the rate of successful sexual intercourse (SSI during the final intercourse attempt using sildenafil 50 mg compared with the subsequent initial attempt after a dose increase to 100 mg.Patients and methods: This post hoc analysis used data from two randomized, double-blind, placebo-controlled studies of flexible-dose sildenafil for the treatment of men with ED, who were given sildenafil 50 mg or matching placebo, to be taken as needed before sexual intercourse. After 2 weeks, those with no tolerability concerns were titrated up to 100 mg, forming the subgroup of this analysis. The main outcome measures were event log data, including an Erection Hardness Score (EHS and a question on SSI (“Did your erection last long enough for you to have successful sexual intercourse?”, for each attempt at sexual intercourse, analyzed by study and treatment group (sildenafil or placebo. Statistical comparisons were conducted by using the Fisher's exact test.Results: In both studies, the sildenafil group had a larger proportion of EHS4 (completely hard and fully rigid erections (P < 0.001 and SSI (P < 0.005 compared with the placebo group, both before and after the dose increase. Between the final 50 mg sildenafil dose and the initial 100 mg sildenafil dose, the outcomes improved and significantly so in the larger study.Conclusion: The improved efficacy with sildenafil 100 mg versus 50 mg, which occurs rapidly, suggests that patients should be encouraged to use 100 mg if they are unable to achieve completely hard and fully rigid erections or SSI with the 50 mg dose

  9. Morning administration of oral methamphetamine dose-dependently disrupts nighttime sleep in recreational stimulant users.

    Science.gov (United States)

    Herrmann, Evan S; Johnson, Patrick S; Bruner, Natalie R; Vandrey, Ryan; Johnson, Matthew W

    2017-09-01

    Use of amphetamine-type stimulants (e.g., methamphetamine) is associated with acute sleep disruptions. No prior reports have characterized the acute effects of methamphetamine on sleep using polysomnography, the gold standard for objective sleep monitoring. Recreational stimulant users (n=19) completed a baseline assessment, which included questionnaires assessing demographic and substance use characteristics, and the Pittsburgh Sleep Quality Index (PSQI), which assesses sleep quality over the past month. Participants were administered 0mg (placebo), 20mg, or 40mg oral methamphetamine at 08:15h on study days, using a double-blind, randomized, within-subjects design. Sleep was monitored using polysomnography from 22:20 that evening until 06:15 the following morning. PSQI scores indicated more than half of participants reported poor sleep quality at baseline. Methamphetamine dose-dependently increased sleep latency, and decreased total sleep time, sleep efficiency, time in NREM 2 sleep, number of REM periods, and total time in REM sleep. Sleep under placebo conditions was consistent with what would be expected from healthy adults. Morning oral administration of methamphetamine produces robust disruptions in nighttime sleep. Future research should examine relations between stimulant use and sleep disruption in naturalistic settings, with regard to both stimulant abuse and licit prescription use. Copyright © 2017. Published by Elsevier B.V.

  10. Desarrollo tecnológico de la suspensión oral de fenoximetilpenicilina 125 mg

    Directory of Open Access Journals (Sweden)

    María de los Ángeles Lorenzo

    1997-08-01

    Full Text Available Se describió el desarrollo tecnológico de una formulación de fenoximetilpenicilina suspensión oral 125 mg para uso pediátrico, utilizando la vía seca que se inicia con la mezcla del principio activo con los sabores, estabilizadores, edulcorantes y lubricantes hasta lograr un producto estable y con las características que lo hacen adecuado para el uso que se destina. Se estudió la estabilidad del producto terminado desde el punto de vista tecnológico y químico con resultados satisfactorios. El medicamento diseñado cumple con los requisitos más actuales para su comercialización y forma parte del surtido estable de producción de la Empresa Farmacéutica "8 de Marzo".The technological development of an oral formulation containing 125 mg of phenoxymethylpenicillin oral suspension for pediatric use is described. The formulation was obtained by a dryness procedure which is initiated mixing the active ingredient with flavours, stabilizings, edulcorates and lubricants until attaining a stable product having the characteristics which make the product being adequate for being used. The stability of the end product was studied from the technological and chemical point of view with satisfactory results. The drug produced complies with the most current requirements for its commercialization and forms part of the stable stock of "8 de Marzo" Pharmaceutical Enterprice.

  11. Desarrollo de la formulación de dicloxacilina, suspensión oral 125 mg

    Directory of Open Access Journals (Sweden)

    María de los Ángeles Lorenzo

    1997-12-01

    Full Text Available Se describe el desarrollo de la formulación de dicloxacilina sódica, suspensión oral 125 mg para uso pediátrico mediante la técnica de elaboración del granulado por la vía humeda. Se logró un producto estable por el tiempo de vida útil de 24 meses y después de reconstituido 10 d.It is described the development of the sodium dicloxacillin formulation, oral suspension for pediatric use by using the technique of elaboration of the granulate by wet way. It was obtained a stable product with a useful life of 24 months, and of 10 days after being reconstituted.

  12. Plasma methylphenidate concentrations in youths treated with high-dose osmotic release oral system formulation.

    Science.gov (United States)

    Stevens, Jonathan R; George, Robert A; Fusillo, Steven; Stern, Theodore A; Wilens, Timothy E

    2010-02-01

    Children and adolescents are being treated increasingly for attention-deficit/hyperactivity disorder (ADHD) with a variety of stimulants in higher than Food and Drug Administration (FDA)-approved doses and in combination with other medications. We sought to determine methylphenidate (MPH) concentrations in children and adolescents treated with high-dose, extended-release osmotic release oral system (OROS) MPH plus concomitant medications, and to examine MPH concentrations with respect to the safety and tolerability of treatment. Plasma MPH concentrations were measured by liquid chromatography-mass spectrometry 4-5 hours after administration of medication in a sample of youths diagnosed with ADHD. These youths were treated naturalistically with higher than FDA-approved doses of OROS MPH in addition to their concomitant medications. Markers of safety and tolerability (e.g., measures of blood pressure and heart rate) were also examined. Among the 17 patients (with a mean age of 16.2 +/- 2 years and a mean number of concurrent medications of 2.23 +/- 0.94), the mean plasma MPH concentration was 28 +/- 9.1 ng/mL, despite a mean daily dose of OROS MPH of 169 +/- 5 mg (3.0 +/- 0.8 mg/kg per day). No patient had a plasma MPH level >or=50 ng/mL or clinical signs of stimulant toxicity. No correlation was found between plasma MPH concentrations and OROS MPH dose or changes in vital signs. High-dose OROS MPH, used in combination with other medications, was not associated with either unusually elevated plasma MPH concentrations or with clinically meaningful changes in vital signs. Study limitations include a single time-point sampling of MPH concentrations, a small sample size, and a lack of outcome measures to address treatment effectiveness.

  13. Evaluation of 500- and 1,000-mg doses of ciprofloxacin for the treatment of chancroid.

    Science.gov (United States)

    Bodhidatta, L; Taylor, D N; Chitwarakorn, A; Kuvanont, K; Echeverria, P

    1988-01-01

    A randomized, double-blind study was performed comparing ciprofloxacin in a 500-mg single dose with 1,000 mg (500-mg doses given 12 h apart) for the treatment of chancroid in Thailand. Haemophilus ducreyi was isolated from 87 (48%) of 180 men with a clinical diagnosis of chancroid. For men with ulcers that were culture positive for H. ducreyi, rates of cure were 100% in the 500-mg group and 98% in the 1,000-mg group. For men with ulcers that were culture negative for H. ducreyi, rates of cure were 93% in the 500-mg group and 96% in the 1,000-mg group. The MIC of ciprofloxacin for 50% of isolates among 85 isolates of H. ducreyi was 0.007 micrograms/ml (range, 0.002 to 0.03 micrograms/ml). No significant adverse effects were detected in either group. These data indicate that both of these treatment regimens are equally effective therapies for chancroid in Thailand. PMID:3293526

  14. Single fixed-dose oral dexketoprofen plus tramadol for acute postoperative pain in adults.

    Science.gov (United States)

    Derry, Sheena; Cooper, Tess E; Phillips, Tudor

    2016-09-22

    the data came from a single study with few participants and events.Adverse events and serious adverse events were not reported consistently for the single dose phase of the studies. In the single dose study, 11% of participants experienced adverse events with dexketoprofen 25 mg plus tramadol 75 mg, which were mostly mild or moderate nausea, vomiting, or dizziness, and typical with these medicines. Rates were lower with placebo and lower doses (very low quality evidence). We downgraded the evidence because the data came from a single study with few participants and events. Information on multiple dosing over three and five days supported a low event rate with the combination. Overall, rates were generally low in all treatment arms, as they were for withdrawals for adverse events or other reasons. A single oral dose of dexketoprofen 25 mg plus tramadol 75 mg provided good levels of pain relief with long duration of action to more people than placebo or the same dose of dexketoprofen or tramadol alone. The magnitude of the effect was similar to other good analgesics. Adverse event rates were low.There is modest uncertainty about the precision of the point estimate for efficacy, but the NNT of 3 is consistent with other analgesics considered effective and commonly used.

  15. Vaginal bleeding following the use of a single dose of 1.5mg ...

    African Journals Online (AJOL)

    Introduction: Recent studies have shown that a single dose of 1.5 mg levonorgestrel is an effective and safe emergency contraceptive but detailed information on its menstrual side effects is lacking. This study assessed the vaginal bleeding patterns in healthy women who used the medication for emergency contraception.

  16. Measurement of extremely low level dose with LiF(Mg,Cu,P) TL chips

    International Nuclear Information System (INIS)

    Zha Ziying; Wang Shoushan; Wu Fang; Chen Guolong; Li Yuanfang; Zhu Jianhuan

    1986-01-01

    This paper presents some of the dosimetric characteristics of newly developed LiF(Mg,Cu,P) TL chips with high signal-to-noise ratio for measurement at the 10 -7 to 10 -4 Gy dose level. Measuring techniques and optimum procedures for annealing and readout are also presented. (author)

  17. [Oral loading dose of phenytoin in the treatment of serial seizures, prevention of seizure recurrence and rapid drug substitution].

    Science.gov (United States)

    Sokić, D; Janković, S M

    1994-01-01

    Over a period of nine months twenty-five epileptic patients were treated with the oral loading dose of phenytoin. The dose ranged from 12 to 23 mg/kg body weight during 1 to 12 hours. In 20 patients with serial seizures or intolerance to other antiepileptic drugs this treatment was effective. Seizures also stopped in 2 of 4 patients with serial partial motor seizures. These 2 patients required both higher loading dose and faster rate of administration than the other patients. A patient with epilepsia partialis continua failed to respond to the treatment. Patients that received phenytoin through the naso-gastric tube, in respect to oral administration, required higher doses to obtain therapeutic plasma levels of phenytoin. One patient had mild nausea, 3 mild dizziness, and 1 tinitus on the first day of the treatment. There was no correlation between a given dose and the achieved phenytoin plasma levels. In our opinion the therapy with oral loading dose of phenytoin is highly effective in the treatment of serial generalized seizures and rapid antiepileptic drug substitution, and partially effective in the prevention of partial motor seizures. It produces only mild and transient side-effects.

  18. A 4-Week Repeated-Dose Oral Toxicity Study of Bojungikgi-Tang in Crl:CD Sprague Dawley Rats

    Directory of Open Access Journals (Sweden)

    Sae-Rom Yoo

    2017-01-01

    Full Text Available Traditional herbal medicines have been used for centuries in Asian countries. However, recent studies have led to increasing concerns about the safety and toxicity of herbal prescriptions. Bojungikgi-tang (BJIGT, a herbal decoction, has been used in Korea to improve physical strength. To establish the safety information, BJIGT water extract was evaluated in a 4-week repeated-dose oral toxicity test in Crl:CD Sprague Dawley rats. BJIGT was orally administered in daily doses of 0, 500, 1000, and 2000 mg/kg/day for 4 weeks via oral gavage in male and female rats. We examined the mortality, clinical signs, body weight change, food intake, organ weights, hematology, serum biochemistry, and urinalysis parameters. No significant changes were observed in mortality, clinical sings, body weight, food intake, organ weights, hematology, serum biochemistry, and urinalysis parameters between the control group and the BJIGT-treated groups in the rats of both sexes. The results indicate that BJIGT did not induce toxic effects at a dose level up to 2000 mg/kg in rats. Thus, this concentration is considered the nonobservable effect dose in rats and is appropriate for a 13-week subchronic toxicity study.

  19. Patient doses during intra-oral radiography in dental offices

    International Nuclear Information System (INIS)

    Sakaino, Rie; Harata, Yasuo; Okano, Tomohiro; Sato, Kenji; Yosue, Takashi; Nishikawa, Keiichi; Sano, Tsukasa; Kobayashi, Ikuo

    2011-01-01

    Measurement of patient entrance dose (PED) and dose area product (DAP) at various dental offices in the Tokyo bay area and comparison of PEDs with the existing diagnostic reference levels recommended in the United Kingdom (UK). The survey included 28 dental clinics categorized by the type of intra-oral radiography used. PED was measured by placing an optically stimulated luminescence dosimeter (OSLD) at the tip of the cone. Exposure parameters were those used for the adult mandibular molar region in the respective clinics. The OSLD readings were calibrated using an ionizing chamber manufactured according to standards of the Japan Quality Assurance Organization. The area (A), of the X-ray beam, was calculated by exposing an X-ray film placed at the tip of the cone and measuring the exposed area. Then the DAP was calculated as the product of PED times A. The PED estimated at various dental clinics differed by a factor of 120. The mean, minimum, maximum, median and third quartile values of PEDs were 4.99, 0.18, 21.7, 3.60 and 5.76 mGy, respectively. At 60-70 kV, PEDs observed in clinics using digital imaging systems were below 2.1 mGy which was lower than that of clinics using films that were E-speed or faster. It was also observed that PEDs were directly proportional to the tube current and exposure time. The mean, minimum, maximum, median and third quartile of DAPs were 13.0, 0.45, 61.4, 9.34 and 13.4 cGy cm 2 , respectively. The DAP values showed a linear correlation coefficient of 0.99 with PED values. Measurement of PED and DAP using OSLD and X-ray film can play a useful role in optimization of radiation protection for patients during intra-oral radiography. This method can be conveniently applied to set up diagnostic reference levels by carrying out mass surveys in Japan. (author)

  20. Reproductive toxicity in rats after chronic oral exposure to low dose of depleted uranium

    International Nuclear Information System (INIS)

    Li Rong; Ai Guoping; Xu Hui; Su Yongping; Cheng Tianmin; Leng Yanbing

    2007-01-01

    Objective: To study the reproductive toxicity in rats induced by low dose of depleted uranium (DU). Methods: Male and female rats(F 0 generation) were exposed to DU in food at doses of 0, 0.4, 4 and 40 mg·kg -1 ·d -1 for 160 days, respectively. Then the activities of enzymes in testis and sexual hormone contents in serum were detected. Mature male rats were mated with female rats exposed to the same doses for 14 days. Pregnant rate and normal labor rate in F 0 rats were detected, as well as the survival rate and weight of F 1 rats within 21 d after birth. Results: No adverse effects of DU on fertility were evident at any dose in F 0 rats. Compared with control group, the rate of pregnancy, normal labor, survival of offspring birth and offspring nurture in F 1 generation of high-dose group reduced to 40.0%, 33.3%, 33.3%, and 33.3%, respectively. The sexual hormone contents in F 0 generation exposed increased, but those in Fl rats decreased significantly. The activities of lactate dehydrogenase-X (LDH-X) decreased in F 1 rats exposed to high-dose of DU, and those of sorbitol dehydrogenase (SDH), LDH and Na + -K + -ATPase decreased in F 1 rats exposed to DU. Conclusions: Reproduction function, growth and development of F 0 rats are not obviously affected after chronic oral exposure to DU, while the toxicity effects in F 1 generation was observed at any dose. (authors)

  1. Single- and Multiple-Dose Study To Determine the Safety, Tolerability, Pharmacokinetics, and Food Effect of Oral MRX-I versus Linezolid in Healthy Adult Subjects.

    Science.gov (United States)

    Eckburg, Paul B; Ge, Yigong; Hafkin, Barry

    2017-04-01

    A multipart phase 1 study was conducted to determine the safety, tolerability, pharmacokinetics, and food effect of the novel oral oxazolidinone, MRX-I, in healthy adults, as well as the tolerability of longer-term exposure of both oral MRX-I and linezolid. Thirty subjects in part 1 received single ascending doses of MRX-I or placebo under fasting or fed condition in a double-blind crossover design. Twelve subjects in part 2 received MRX-I at 800 mg every 12 h (q12h) for 14 days in a double-blind, placebo-controlled design. In part 3, 24 subjects were randomized to receive 28 days of MRX-I at 800 mg q12h or oral linezolid at 600 mg q12h for 28 days in a double-blind, double-dummy design. Oral MRX-I was associated with a greater bioavailability and exposure when administered with food, and minimal accumulation of MRX-I occurred after multiple-dose administration. Oral MRX-I was well tolerated at single doses of up to 1,200 and 800 mg q12h for up to 28 days; all adverse events were mild to moderate in severity, and there was no drug discontinuation due to adverse events. These data support further clinical development of oral MRX-I in the treatment of resistant Gram-positive bacterial infections. Copyright © 2017 American Society for Microbiology.

  2. Comparação da eficácia de doses iguais de acetaminofeno retal e oral em crianças Comparison of antipyretic effectiveness of equal doses of rectal and oral acetaminophen in children

    Directory of Open Access Journals (Sweden)

    Sedigha Akhavan Karbasi

    2010-06-01

    Full Text Available OBJETIVO: Comparar uma dose de acetaminofeno oral e retal e avaliar a aceitabilidade do acetaminofeno retal, uma vez que o acetaminofeno oral e retal é amplamente usado como agente antipirético em crianças com febre e a eficiência comparativa dessas duas preparações não está bem estabelecida. MÉTODOS: Neste estudo prospectivo de grupos paralelos, foram incluídas 60 crianças admitidas na emergência ou clínica ambulatorial pediátrica em um hospital terciário, com idade entre 6 meses e 6 anos e com temperatura retal acima de 39 °C. Os pacientes foram distribuídos aleatoriamente em dois grupos de mesmo tamanho. O grupo 1 recebeu 15 mg/kg de acetaminofeno retal, e o grupo 2 recebeu a mesma dose oralmente. A temperatura foi registrada no tempo zero e 1 e 3 horas após administração da droga. RESULTADOS: No primeiro grupo, a redução média de temperatura, 1 e 3 horas após administração do acetaminofeno, foi de 1,07±0,16 (p 0,05. CONCLUSÃO: As preparações oral e retal de acetaminofeno têm eficácia antipirética equivalente em crianças. A via retal mostrou ser tão aceitável quanto a oral entre os pais.OBJECTIVE: To compare a dose of oral and rectal acetaminophen and to evaluate acceptability of rectal acetaminophen, since oral and rectal acetaminophen is widely used as an antipyretic agent in febrile children and the comparative effectiveness of these two preparations is not well established. METHODS: In this prospective parallel group designed study, 60 children who presented to the emergency department or outpatient pediatric clinic at a tertiary hospital and aged from 6 months to 6 years with rectal temperature over 39 °C were enrolled. Patients were randomly assigned to two equal-sized groups. Group 1 received 15 mg/kg acetaminophen rectally and group 2 received the same dose orally. Temperature was recorded at baseline and 1 and 3 hours after drug administration. RESULTS: In the first group, mean decrease in

  3. A study of dose-proportionality in the pharmacokinetics of the oral direct renin inhibitor aliskiren in healthy subjects.

    Science.gov (United States)

    Limoges, D; Dieterich, H A; Yeh, C-M; Vaidyanathan, S; Howard, D; Dole, W P

    2008-05-01

    To evaluate the dose-proportionality of the pharmacokinetics of aliskiren, the first in a new class of orally active direct renin inhibitors approved for the treatment of hypertension. This was an open-label, single-center, single-dose, randomized, 4-period crossover study. Following a 21-day screening period, 32 healthy male or female subjects (ages 18 - 45 years) were randomized to 1 of 4 aliskiren dosing sequence groups (8 subjects per group): 75, 150, 300 and 600 mg. Blood samples were obtained for determination of plasma aliskiren concentrations (HPLC/MS/MS) for 96 h post dose. Log-transformed pharmacokinetic parameters AUC and C(max) were analyzed to determine dose-proportionality using the power model, parameter = A*(Dose)(beta), where A = intercept and beta = dose-proportionality coefficient. The predefined dose-proportionality criteria over the dose range 75 â 600 mg were 90% confidence intervals (CI) for beta contained within the range 0.89 - 1.11. AUC and Cmax values increased with increasing doses of aliskiren. Both AUC and C(max) were associated with high variability (coefficient of variation 55 - 64% for AUC and 59 - 117% for C(max)). The estimated proportionality coefficients (beta) for AUC(0-infiniti), AUC(0-t) and C(max) were 1.18 (90% CI 1.10, 1.25), 1.29 (90% CI 1.22, 1.36) and 1.42 (90% CI 1.31, 1.52), respectively. Dose-proportionality was, therefore, not demonstrated across the entire 8-fold dose range. For the clinical dose range of 150 â 300 mg, increases of 2.3- and 2.6-fold were observed for AUC and C(max), respectively. All doses of aliskiren were well tolerated. Exposure to aliskiren was greater than proportional over the dose range of 75 - 600 mg. Over the therapeutic dose range of 150 â 300 mg approved for the treatment of hypertension, AUC and Cmax increased by 2.3- and 2.6-fold, respectively. The pharmacokinetics of aliskiren show relatively high intersubject variability.

  4. Effects of a single 1200-mg preoperative dose of gabapentin on anxiety and memory.

    Science.gov (United States)

    Adam, F; Bordenave, L; Sessler, D I; Chauvin, M

    2012-10-01

    Gabapentin has antihyperalgesic and potential anxiolytic effects. We therefore evaluated the effects of gabapentin premedication on anxiety, amnesia, and sedation. We tested the primary hypothesis that 1200mg of oral gabapentin 2 to 3h before surgery reduces preoperative anxiety. Our secondary hypothesis was that gabapentin administration is sedative without causing preoperative amnesia. Prospective, randomized and placebo-controlled study. Surgical patients having general anaesthesia were randomly assigned to either 1200mg oral gabapentin (n=32) or an identical-looking placebo (n=32) 2 to 3h before anaesthesia. Anxiety, sedation, and amnesia were quantified before premedication, 2h thereafter, and postoperatively. Preoperative anxiety was measured using the Spielberger state trait anxiety inventory (STAI state) and the visual analogue scale anxiety (VAS). Memory was assessed with the picture recall test of Snodgrass and Vanderwart. Results were compared with t, Mann-Whitney U, or Chi(2) tests as appropriate, Psedation scores. Gabapentin premedication, 1200mg, provided preoperative anxiolysis without causing sedation or impairing preoperative memory. Copyright © 2012 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier SAS. All rights reserved.

  5. Acute oral administration of low doses of methylphenidate targets calretinin neurons in the rat septal area.

    Directory of Open Access Journals (Sweden)

    Alvaro eGarcía-Aviles

    2015-03-01

    Full Text Available Methylphenidate (MPD is a commonly administered drug to treat children suffering from attention deficit hyperactivity disorder (ADHD. Alterations in septal driven hippocampal theta rhythm may underlie attention deficits observed in these patients. Amongst others, the septo-hippocampal connections have long been acknowledged to be important in preserving hippocampal function. Thus, we wanted to ascertain if methylphenidate administration, which improves attention in patients, could affect septal areas connecting with hippocampus. We used low and orally administered methylphenidate doses (1.3; 2.7 and 5mg/Kg to rats what mimics the dosage range in humans. In our model, we observed no effect when using 1.3mg/Kg methylphenidate; whereas 2.7 and 5 mg/Kg induced a significant increase in c-fos expression specifically in the medial septum, an area intimately connected to the hippocampus. We analyzed dopaminergic areas such as nucleus accumbens and striatum, and found that only 5mg/Kg induced c-fos levels increase. In these areas tyrosine hydroxylase correlated well with c-fos staining, whereas in the medial septum the sparse tyrosine hydroxylase fibres did not overlap with c-fos positive neurons. Double immunofluorescence of c-fos with neuronal markers in the septal area revealed that co-localization with choline acethyl transferase, parvalbumin, and calbindin with c-fos did not change with MPD treatment; whereas, calretinin and c-fos double labeled neurons increased after MPD administration. Altogether, these results suggest that low and acute doses of methylphenidate primary target specific populations of caltretinin medial septal neurons.

  6. Safety, tolerability, and pharmacokinetics of single oral doses of tofacitinib, a Janus kinase inhibitor, in healthy volunteers.

    Science.gov (United States)

    Krishnaswami, Sriram; Boy, Mary; Chow, Vincent; Chan, Gary

    2015-03-01

    Tofacitinib is an oral Janus kinase inhibitor. This randomized, double-blind, parallel-group, placebo-controlled study was the first evaluation of tofacitinib in humans. The objectives were to characterize the safety and tolerability, pharmacokinetics (PK), and pharmacodynamics of escalating single tofacitinib doses in healthy subjects. Tofacitinib (0.1, 0.3, 1, 3, 10, 30, 60, and 100 mg) or placebo was administered as oral powder for constitution. For each dose, 7-9 subjects were randomized to tofacitinib and 3-5 subjects to placebo. Ninety-five males and females (age range 19-45) completed the study. Forty-nine treatment-emergent all-causality adverse events (AEs) were observed; nausea and headache were the most frequently reported. Tofacitinib PK was characterized by rapid absorption (time to peak serum concentration [Tmax ] 0.5-1 hour), rapid elimination (mean terminal half-lives 2.3-3.1 hours), and dose-proportional systemic exposures (peak serum concentration [Cmax ] and area under the serum concentration-time curve from time zero to infinity [AUC0-∞ ]). No appreciable correlation was observed between tofacitinib dose and lymphocyte subset counts. Single-dose tofacitinib up to 100 mg in healthy subjects had a safety profile of mostly mild AEs, and no deaths, serious AEs, severe AEs or discontinuations due to AEs. © 2014, The American College of Clinical Pharmacology.

  7. Reversal of rocuronium-induced (1.2 mg kg-1) profound neuromuscular block by accidental high dose of sugammadex (40 mg kg-1).

    NARCIS (Netherlands)

    Molina, A.L.; Boer, H.D. de; Klimek, M.; Heeringa, M.; Klein, J.

    2007-01-01

    Sugammadex is the first selective relaxant binding agent and reverses rocuronium-induced neuromuscular block. A case is reported in which a patient accidentally received a high dose of sugammadex (40 mg kg-1) to reverse a rocuronium-induced (1.2 mg kg-1) profound neuromuscular block. A fast and

  8. Evaluation of Genotoxicity and 28-day Oral Dose Toxicity on Freeze-dried Powder of Tenebrio molitor Larvae (Yellow Mealworm).

    Science.gov (United States)

    Han, So-Ri; Yun, Eun-Young; Kim, Ji-Young; Hwang, Jae Sam; Jeong, Eun Ju; Moon, Kyoung-Sik

    2014-06-01

    The larval form of Tenebrio molitor (T. molitor) has been eaten in many countries and provides benefits as a new food source of protein for humans. However, no information exists regarding its safety for humans. The objective of the present study was to evaluate the genotoxicity and repeated dose oral toxicity of the freeze-dried powder of T. molitor larvae. The genotoxic potential was evaluated by a standard battery testing: bacterial reverse mutation test, in vitro chromosome aberration test, and in vivo micronucleus test. To assess the repeated dose toxicity, the powder was administered once daily by oral gavage to Sprague-Dawley (SD) rats at dose levels of 0, 300, 1000 and 3000 mg/kg/day for 28 days. The parameters which were applied to the study were mortality, clinical signs, body and organ weights, food consumption, ophthalmology, urinalysis, hematology, serum chemistry, gross findings and histopathologic examination. The freezedried powder of T. molitor larvae was not mutagenic or clastogenic based on results of in vitro and in vivo genotoxicity assays. Furthermore, no treatment-related changes or findings were observed in any parameters in rats after 28 days oral administration. In conclusion, the freeze-dried powder of T. molitor larvae was considered to be non-genotoxic and the NOAEL (No Observed Adverse Effect Level) was determined to be 3000 mg/kg/day in both sexes of SD rats under our experimental conditions.

  9. Evaluation of Genotoxicity and 28-day Oral Dose Toxicity on Freeze-dried Powder of Tenebrio molitor Larvae (Yellow Mealworm)

    Science.gov (United States)

    Han, So-Ri; Yun, Eun-Young; Kim, Ji-Young; Hwang, Jae Sam; Jeong, Eun Ju

    2014-01-01

    The larval form of Tenebrio molitor (T. molitor) has been eaten in many countries and provides benefits as a new food source of protein for humans. However, no information exists regarding its safety for humans. The objective of the present study was to evaluate the genotoxicity and repeated dose oral toxicity of the freeze-dried powder of T. molitor larvae. The genotoxic potential was evaluated by a standard battery testing: bacterial reverse mutation test, in vitro chromosome aberration test, and in vivo micronucleus test. To assess the repeated dose toxicity, the powder was administered once daily by oral gavage to Sprague-Dawley (SD) rats at dose levels of 0, 300, 1000 and 3000 mg/kg/day for 28 days. The parameters which were applied to the study were mortality, clinical signs, body and organ weights, food consumption, ophthalmology, urinalysis, hematology, serum chemistry, gross findings and histopathologic examination. The freezedried powder of T. molitor larvae was not mutagenic or clastogenic based on results of in vitro and in vivo genotoxicity assays. Furthermore, no treatment-related changes or findings were observed in any parameters in rats after 28 days oral administration. In conclusion, the freeze-dried powder of T. molitor larvae was considered to be non-genotoxic and the NOAEL (No Observed Adverse Effect Level) was determined to be 3000 mg/kg/day in both sexes of SD rats under our experimental conditions. PMID:25071922

  10. The Protective Effects of Oral Low-dose Quercetin on Diabetic Nephropathy in Hypercholesterolemic Mice

    Directory of Open Access Journals (Sweden)

    Isabele Beserra Santos Gomes

    2015-09-01

    Full Text Available Aims: Diabetic nephropathy (DN is one of the major causes of end-stage renal disease, and the incidence of DN is increasing worldwide. Considering our previous report indicating that chronic treatment with oral low-dose quercetin (10 mg/Kg demonstrated renoprotective, anti-oxidative and anti-apoptotic effects in the C57BL/6J model of diabetic nephropathy, we investigated whether this flavonoid could also have beneficial effects in concurrent DN and spontaneous atherosclerosis using the apolipoprotein E-deficient mouse (apoE-/-. Methods: DN was induced by streptozotocin (100 mg/kg/day, for 3 days in adult apoE-/-mice. Six weeks later, the mice were divided into the following groups: diabetic apoE-/- mice treated with quercetin (DQ, 10 mg/kg/day, 4 weeks, diabetic ApoE-/- mice treated with vehicle (DV and non-treated non-diabetic (ND mice.Results: Quercetin treatment caused a reduction in polyuria (~30%, glycemia (~25%, abolished the hypertriglyceridemia and had significant effects on renal function, including decreased proteinuria (~15% and creatininemia (~30%, which were accompanied by beneficial effects on the renal structural changes, including normalization of the index of glomerulosclerosis and kidney weight.Conclusions: Our data revealed that quercetin treatment significantly reduced DN in hypercholesterolemic mice by inducing biochemical and morphological modifications. Thus, this translational study highlights the importance of quercetin as a potential nutraceutical for the management of DN, including in diabetes associated with dyslipidemia.

  11. Safety and Efficacy of Low-Dose Oral Immunotherapy for Hen's Egg Allergy in Children.

    Science.gov (United States)

    Yanagida, Noriyuki; Sato, Sakura; Asaumi, Tomoyuki; Nagakura, Kenichi; Ogura, Kiyotake; Ebisawa, Motohiro

    2016-01-01

    The minimal dose for oral immunotherapy (OIT) tolerance is unknown. We investigated the efficacy and safety of low-dose OIT with 1/32 of the volume of a whole egg. Thirty-three children (aged ≥5 years) with egg allergies confirmed by oral food challenge against 1/32 of a heated whole egg (194 mg of egg protein) were enrolled. The OIT group ingested a scrambled egg once a day. The volume was gradually increased up to a maximum of 1/32 of a heated whole egg. Egg consumption was completely absent in the control group. There were no significant differences in background between the OIT and control groups. Respectively, 71% (15/21) and 0% (0/12) of the patients in the OIT and control groups exhibited sustained unresponsiveness to 1/32 of a whole egg 2 weeks after stopping OIT after 12 months (p egg. Egg white- or ovomucoid-specific IgE levels in the OIT group were significantly lower than at baseline after 12 months. Egg white- or ovomucoid-specific IgG as well as IgG4 levels in the OIT group were significantly higher than baseline levels after 1, 3, 6, and 12 months. Adverse allergic reactions were rare, and most symptoms were mild. Low-dose OIT induced sustained unresponsiveness to 1/32 and 1/2 of a whole egg, with no severe symptoms. To improve food allergies, continuous intake of small amounts of these foods may be as effective as the consumption of larger quantities. © 2017 The Author(s) Published by S. Karger AG, Basel.

  12. Pharmacokinetic/pharmacodynamic modeling of benazepril and benazeprilat after administration of intravenous and oral doses of benazepril in healthy horses.

    Science.gov (United States)

    Serrano-Rodríguez, Juan Manuel; Gómez-Díez, Manuel; Esgueva, María; Castejón-Riber, Cristina; Mena-Bravo, Antonio; Priego-Capote, Feliciano; Ayala, Nahúm; Caballero, Juan Manuel Serrano; Muñoz, Ana

    2017-10-01

    Pharmacokinetic and pharmacodynamic (PK/PD) properties of the angiotensin-converting enzyme inhibitor (ACEI) benazeprilat have not been evaluated in horses. This study was designed to establish PK profiles for benazepril and benazeprilat after intravenous (IV) and oral (PO) administration of benazepril using a PK/PD model. This study also aims to determine the effects of benazeprilat on serum angiotensin converting enzyme (ACE), selecting the most appropriate dose that suppresses ACE activity. Six healthy horses in a crossover design received IV benazepril at 0.50mg/kg and PO at doses 0 (placebo), 0.25, 0.50 and 1.00mg/kg. Blood pressures (BP) were measured and blood samples were obtained at different times in order to measure serum drug concentrations and serum ACE activity, using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and spectrophotometry, respectively. Systemic bioavailability of benazeprilat after PO benazepril was 3-4%. Maximum ACE inhibitions from baseline were 99.63% (IV benazepril), 6.77% (placebo) and 78.91%, 85.74% and 89.51% (for the three PO benazepril doses). Significant differences in BP were not found. Although oral availability was low, benazeprilat 1.00mg/kg, reached sufficient serum concentrations to induce long lasting serum ACE inhibitions (between 88 and 50%) for the first 48h. Additional research on benazepril administration in equine patients is indicated. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. A comparison of the effect of two doses of oral melatonin with oral midazolam and placebo on pre-operative anxiety, cognition and psychomotor function in children: A randomised double-blind study

    Directory of Open Access Journals (Sweden)

    Madhuri S Kurdi

    2016-01-01

    Full Text Available Background and Aims: Melatonin (MT, a naturally occurring pituitary hormone has a sleep promoting effect. There are very few studies on pre-operative oral MT (0.2-0.5 mg/kg in children. We planned a study to assess the efficacy of oral MT in two doses and compare it with oral midazolam and placebo for pre-operative anxiolysis, sedation, maintenance of cognition and psychomotor skills, parental separation behaviour and venepuncture compliance. Methods: This prospective double-blind randomised study was conducted after ethical committee approval on 100 children aged 5-15 years, American Society of Anaesthesiologists physical status I and II undergoing elective surgery at our hospital from January 1, 2014, to December 31, 2014. Mentally disordered children were excluded from the study. They were randomised into four groups of 25 each (A, B, C, D to receive either oral MT 0.5 mg/kg or 0.75 mg/kg or oral midazolam 0.5 mg/kg or placebo 45-60 min, respectively, before induction. The child′s anxiety, cognition and psychomotor function before and after pre-medication, behaviour during the parental separation and venepuncture were appropriately scored. Kruskal-Wallis analysis of variance for intergroup and Wilcoxon matched pairs tests for intragroup comparisons of data were applied. Results: The four groups were comparable regarding mean age, weight and sex. The anxiety score reductions in the three groups when compared to placebo were statistically significant. Children receiving MT 0.75 mg/kg had maximum anxiolysis and venepuncture compliance (P < 0.05. Cognition was decreased with maximum sedation, successful parental separation and psychomotor impairment in the midazolam group (P < 0.05. Conclusion: Oral MT (0.5 mg/kg and 0.75 mg/kg in children decreases pre-operative anxiety without impairing cognitive and psychomotor functions, the 0.75 mg/kg dose being most effective.

  14. Treatment with acetaminophen/paracetamol or ibuprofen alleviates post-dose symptoms related to intravenous infusion with zoledronic acid 5 mg.

    Science.gov (United States)

    Wark, J D; Bensen, W; Recknor, C; Ryabitseva, O; Chiodo, J; Mesenbrink, P; de Villiers, T J

    2012-02-01

    Patients treated with intravenous zoledronic acid 5 mg for osteoporosis may experience post-dose influenza-like symptoms. Oral acetaminophen/paracetamol or ibuprofen administered 4 h post-infusion reduced the proportion of patients with increased oral temperature and worsening post-infusion symptom scores vs. placebo, thus providing an effective strategy for the treatment of such symptoms. Once-yearly intravenous zoledronic acid 5 mg is a safe and effective treatment for postmenopausal osteoporosis. This study assessed whether transient influenza-like post-dose symptoms associated with intravenous infusion of zoledronic acid can be reduced by post-dose administration of acetaminophen/paracetamol or ibuprofen. In an international, multicenter, randomized, double-blind, double-dummy parallel-group study, bisphosphonate-naïve postmenopausal women with osteopenia (n = 481) were randomized to receive zoledronic acid 5 mg + acetaminophen/paracetamol (n = 135), ibuprofen (n = 137) or placebo (n = 137), or placebo + placebo (n = 72). Acetaminophen/paracetamol and ibuprofen were administered every 6 h for 3 days beginning 4 h post-infusion. The proportion of patients with increased oral temperature (≥1°C above 37.5°C) and with worsening post-infusion symptom scores over 3 days was significantly lower in patients receiving ibuprofen (36.8% and 48.5%) or acetaminophen/paracetamol (37.3% and 46.3%) vs. those receiving placebo (63.5% and 75.9%, respectively; all p paracetamol or ibuprofen. Oral acetaminophen/paracetamol or ibuprofen effectively managed the transient influenza-like symptoms associated with zoledronic acid 5 mg.

  15. Induction of oral tolerance with micro-doses of ovomucoid depends on the length of the feeding period

    DEFF Research Database (Denmark)

    Kjær, Tanja; Frøkiær, Hanne

    2002-01-01

    Oral administration of antigen induces antigen-specific immunologic tolerance, which is known to be dose-dependent. We studied the influence of continuous oral administration of nanogram and microgram doses of antigen on oral tolerance induction. Mice were continuously exposed to varying doses (1...

  16. A Study on the Single-dose Oral Toxicity of Super Key in Sprague-Dawley Rats

    Directory of Open Access Journals (Sweden)

    Jinhee Kim

    2015-09-01

    Full Text Available Objectives: This study was performed to analyze the single-dose oral toxicity of the super key (processed sulfur. Methods: All experiments were conducted at Medvill, an institution authorized to perform non-clinical studies, under the Good Laboratory Practice (GLP regulations. In order to investigate the oral toxicity of super key We administered it orally to Sprague-Dawley (SD rats. The SD rats were divided into four groups of five male and five female animals per group: group 1 being the control group and groups 2, 3, and 4 being the experimental groups. Doses of super key 500 mg/kg, 1,000 mg/kg and 2,000 mg/kg were administered to the experimental groups, and a dose of normal saline solution, 10 mL/kg, was administered to the control group. We examined the survival rates, weights, clinical signs, gross findings and necropsy findings. This study was conducted under the approval of the Institutional Animal Ethics Committee. (Approval number: A01-14018. Results: No deaths or abnormalities occurred in any of the four groups. Although slight decreases in the weights of some female rats were noted, no significant changes in weights or differences in the gross findings between the control group and the experimental groups were observed. To check for abnormalities in organs, we used microscopy to examine representative histological sections of each specified organ; the results showed no significant differences in any of the organs. Conclusion: The results of this research showed that administration of 500 ─ 2,000 mg/kg of super key did not cause any changes in the weights or in the results of necropsy examinations. Neither did it result in any mortalities. The above findings suggest that treatment with super key is relatively safe. Further studies on this subject are needed to yield more concrete evidence.

  17. Oral cryotherapy for the prevention of high-dose melphalan-induced stomatitis in allogeneic hematopoietic stem cell transplant recipients.

    Science.gov (United States)

    Aisa, Yoshinobu; Mori, Takehiko; Kudo, Masumi; Yashima, Tomoko; Kondo, Sakiko; Yokoyama, Akihiro; Ikeda, Yasuo; Okamoto, Shinichiro

    2005-04-01

    The purpose of this study was to evaluate the efficacy of oral cryotherapy to prevent high-dose melphalan-induced stomatitis. Eighteen consecutive recipients of allogeneic hematopoietic stem cell transplant conditioned with high-dose melphalan (140 mg/m2) in combination with fludarabine alone or with fludarabine and additional chemotherapy or radiation were enrolled. The severity of stomatitis was graded according to the National Cancer Institute Common Toxicity Criteria. Patients were kept on oral cryotherapy using ice chips and ice-cold water shortly before, during, and for additional 90 min after completion of melphalan administration. Only two of 18 patients (11.1%) developed grade 2 or 3 stomatitis while six of seven patients in the historical control developed it (85.7%; P=0.001). These results suggested that oral cryotherapy could effectively prevent stomatitis caused by high-dose melphalan, and we recommend that it should be incorporated into the conditioning regimen with high-dose melphalan.

  18. Fevipiprant, an oral prostaglandin DP2 receptor (CRTh2) antagonist, in allergic asthma uncontrolled on low-dose inhaled corticosteroids.

    Science.gov (United States)

    Bateman, Eric D; Guerreros, Alfredo G; Brockhaus, Florian; Holzhauer, Björn; Pethe, Abhijit; Kay, Richard A; Townley, Robert G

    2017-08-01

    Dose-related efficacy and safety of fevipiprant (QAW039), an oral DP 2 (CRTh2) receptor antagonist, was assessed in patients with allergic asthma uncontrolled by low-dose inhaled corticosteroids (ICS).Adult patients were randomised to 12 weeks' treatment with once-daily (1, 3, 10, 30, 50, 75, 150, 300 or 450 mg q.d ) or twice-daily (2, 25, 75 or 150 mg b.i.d ) fevipiprant (n=782), montelukast 10 mg q.d (n=139) or placebo (n=137). All patients received inhaled budesonide 200 μg b.i.d Fevipiprant produced a statistically significant improvement in the primary end-point of change in pre-dose forced expiratory volume in 1 s at week 12 (p=0.0035) with a maximum model-averaged difference to placebo of 0.112 L. The most favourable pairwise comparisons to placebo were for the fevipiprant 150 mg q.d and 75 mg b.i.d groups, with no clinically meaningful differences between q.d and b.i.d Montelukast also demonstrated a significant improvement in this end-point. No impact on other efficacy end-points was observed. Adverse events were generally mild/moderate in severity, and were evenly distributed across doses and treatments.Fevipiprant appears to be efficacious and well-tolerated in this patient population, with an optimum total daily dose of 150 mg. Further investigations into the clinical role of fevipiprant in suitably designed phase III clinical trials are warranted. Copyright ©ERS 2017.

  19. A multiple-dose, double-blind comparison of intramuscularly and orally administered ketorolac tromethamine and Ketogan in patients with pain following orthopaedic surgery

    DEFF Research Database (Denmark)

    Gebuhr, Peter Henrik; Soelberg, M; Strauss, W

    1994-01-01

    combination product containing the narcotic analgesic, ketobemidone, plus a spasmolytic agent) by intramuscular injection every 1-6 h as needed for pain. When patients were able to tolerate an oral diet and were expected to respond to oral analgesic medication, based on overall pain sensitivity, they were...... and at the end of each day. Both treatments were effective immediately after the first dose and during the subsequent multiple-dose phase. There were no statistically significant differences between ketorolac and Ketogan. The results show that 10-mg doses of ketorolac in intramuscular injections followed by 10......In this multiple-dose, double-blind study 100 patients with moderate, severe or very severe pain following orthopaedic surgery were randomly assigned to receive ketorolac, a non-steroidal anti-inflammatory drug with potent analgesic properties (10 mg), or the standard regimen of Ketogan (a...

  20. Single dose oral ranitidine improves MRCP image quality: a double-blind study

    International Nuclear Information System (INIS)

    Bowes, M.T.; Martin, D.F.; Melling, A.; Roberts, D.; Laasch, H.-U.; Sukumar, S.; Morris, J.

    2007-01-01

    Aim: To investigate the possibility of whether a single 300 mg dose of ranitidine given orally 2-3 h before magnetic resonance cholangiopancreatography (MRCP) could reduce the signal from the stomach and duodenum, and thus increase the conspicuousness of the biliary tree. Materials and methods: Thirty-five volunteers (22 female, 13 male), (age range 21-50) were underwent MRCP in a double-blind, placebo-controlled, randomized, crossover trial on a Philips Intera 1.5 T machine using a phased array surface coil. Imaging was carried out in the coronal oblique plane. Six 40 mm sections were acquired at varying angles to delineate the biliary tree and pancreatic duct. The 70 examinations were blindly scored by three consultants experienced in cholangiography. Results: After ranitidine administration there was a significant decrease in signal from the stomach (mean = 17.7, p = 0.0005, CI 10, 25.3) and duodenum (mean = 18.4, p = 0.0005, 95%CI 9.6, 27.1) with a significant increase in conspicuousness of the distal common duct (mean = 7.7, p = 0.033, 95%CI 0.7, 14.7) and proximal common duct (mean = 8.7, p = 0.010 CI 2.2, 15.2). There were no adverse effects. Conclusion: Oral ranitidine is a cheap and effective agent to decrease signal from the upper gastrointestinal tract and to improve visibility of the biliary tree

  1. Hardness, function, emotional well-being, satisfaction and the overall sexual experience in men using 100-mg fixed-dose or flexible-dose sildenafil citrate

    Science.gov (United States)

    Ströberg, P; Kaminetsky, J C; Park, N C; Goldfischer, E R; Creanga, D L; Stecher, V J

    2010-01-01

    The prescribing information for sildenafil citrate (VIAGRA, Pfizer, New York, NY, USA) recommends flexible dosing (50 mg initially, adjusted to 100 or 25 mg based on effectiveness and tolerability) in most men with erectile dysfunction (ED). In many men, however, 100 mg may be the most appropriate initial dose because it would reduce the need for titration and could prevent discouragement and treatment abandonment should 50 mg be insufficient. Results of two previously published double-blind, placebo-controlled sildenafil trials of similar design except for a fixed-dose vs flexible-dose regimen were analyzed. Relative to the flexible-dose, approximately one-third more men were satisfied with an initial and fixed dose of 100 mg. In addition, tolerability was similar, and improvements from baseline in outcomes on validated, ED-specific, patient-reported questionnaires were either similar (erectile function and the percentage of completely hard and fully rigid erections) or greater (emotional well-being and the overall sexual experience). The similarity in outcomes is not surprising given that almost 90% of the men in the flexible-dose trial titrated to 100 mg after 2 weeks. These data suggest prescription of an initial dose of 100 mg for men with ED, except in those for whom it is inappropriate. PMID:20596083

  2. Hardness, function, emotional well-being, satisfaction and the overall sexual experience in men using 100-mg fixed-dose or flexible-dose sildenafil citrate.

    Science.gov (United States)

    Ströberg, P; Kaminetsky, J C; Park, N C; Goldfischer, E R; Creanga, D L; Stecher, V J

    2010-01-01

    The prescribing information for sildenafil citrate (VIAGRA, Pfizer, New York, NY, USA) recommends flexible dosing (50 mg initially, adjusted to 100 or 25 mg based on effectiveness and tolerability) in most men with erectile dysfunction (ED). In many men, however, 100 mg may be the most appropriate initial dose because it would reduce the need for titration and could prevent discouragement and treatment abandonment should 50 mg be insufficient. Results of two previously published double-blind, placebo-controlled sildenafil trials of similar design except for a fixed-dose vs flexible-dose regimen were analyzed. Relative to the flexible-dose, approximately one-third more men were satisfied with an initial and fixed dose of 100 mg. In addition, tolerability was similar, and improvements from baseline in outcomes on validated, ED-specific, patient-reported questionnaires were either similar (erectile function and the percentage of completely hard and fully rigid erections) or greater (emotional well-being and the overall sexual experience). The similarity in outcomes is not surprising given that almost 90% of the men in the flexible-dose trial titrated to 100 mg after 2 weeks. These data suggest prescription of an initial dose of 100 mg for men with ED, except in those for whom it is inappropriate.

  3. Perbandingan Gabapentin 600 mg dengan 1.200 mg per Oral Preoperatif terhadap Nilai Visual Analogue Scale dan Pengurangan Kebutuhan Petidin Pascaoperasi pada Modifikasi Mastektomi Radikal

    Directory of Open Access Journals (Sweden)

    Ardi Zulfariansyah

    2013-12-01

    Full Text Available Gabapentin is a GABA analog which has the effect of anti hyperalgesia, anti allodynia, and anti nociceptive. This research was conducted in order to assess the effect of 600mg and 1,200 mg gabapentin given preoperatively to assess visual analogue scale (VAS score and reduction of pethidine requirement. The study was done by conducting a double blind randomized controlled trial on 38 patients, aged 18–65 years, with ASA physical status I–II. Patients were divided into two groups: 600 mg gabapentin and 1,200 mg gabapentin group. The quality of pain was assessed using VAS score. The results were statistically analyzed using Mann-Whitney Test with 95% confidence interval and considered significant if p value <0.05. From the results, the VAS values obtained at rest and during mobilization were significantly different (p<0.05. The 1,200 mg gabapentin group received less additional pethidine (10.5% vs 15.8%, although no significant difference was shown (p=0.631. The conclusion of this study is that administration of 1,200 mg gabapentin per oral pre operatively is better when compared to 600 mg in reducing post operative visual analog scale score in modified radical mastectomy. However, it do not reduce the need for analgesic significantly.

  4. Dose requirements of alfentanil to eliminate autonomic responses during rapid-sequence induction with thiopental 4 mg/kg and rocuronium 0.6 mg/kg.

    Science.gov (United States)

    Abou-Arab, Mohammad H; Rostrup, Morten; Heier, Tom

    2016-12-01

    Opioids are integral part of anesthesia induction, but information on optimal dosing is limited. We aimed to determine doses of alfentanil needed to eliminate increases in 5 autonomic response variables (plasma concentrations of epinephrine, norepinephrine and vasopressin, arterial blood pressure [ABP], and heart rate) during rapid-sequence induction of anesthesia with thiopental 4 mg/kg and rocuronium 0.6 mg/kg. Prospective, randomized, observer-blinded, interventional clinical study. Large academic institution. Eighty-four healthy patients, aged 18 to 55 years, received 1 of 7 assessor-blinded doses of alfentanil (0, 10, 20, 30, 40, 50, and 60 μg/kg) together with thiopental 4 mg/kg and rocuronium 0.6 mg/kg, administered in rapid succession (15 seconds). Laryngoscopy was initiated 40 seconds after rocuronium, and tracheal intubation was concluded within 15 seconds thereafter. An indwelling radial artery catheter was used for hemodynamic monitoring and blood sampling. Relationships between alfentanil dose and response variables were tested with linear regression, and the influence of covariates (sex, body weight, and age) was determined. Alfentanil dose needed to prevent increases in ABP >10% above baseline with 95% probability was estimated with logistic regression. Significant relationships were determined between alfentanil dose and response variables. Clinically interesting influence of covariates was not found. Alfentanil 55 μg/kg was needed to prevent increases in ABP postintubation >10% above baseline with 95% probability. One individual needed a bolus of vasopressor postintubation. Optimal control of autonomic responses during rapid-sequence induction was achieved with clinically relevant doses of alfentanil in healthy patients anesthetized with thiopental 4 mg/kg and rocuronium 0.6 mg/kg. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. The effects of lower than conventional doses of oral nadolol on relative beta 1/beta 2-adrenoceptor blockade.

    Science.gov (United States)

    Wheeldon, N M; McDevitt, D G; Lipworth, B J

    1994-08-01

    1. The aim of the present study was to evaluate the relative beta 1/beta 2 antagonist selectivity of the beta-adrenoceptor blocker nadolol, in lower than conventional clinical doses. 2. Eight normal volunteers received single oral doses of either placebo (PL), nadolol 5 mg (N5), 20 mg (N20) or 80 mg (N80) in a single-blind, randomised crossover design. beta 1-adrenoceptor antagonism was assessed by attenuation of exercise tachycardia, and beta 2-adrenoceptor blockade by effects on salbutamol-induced chronotropic, hypokalaemic and finger tremor responses. The relative percentage attenuation of beta 2 and beta 1-mediated responses was calculated and expressed as beta 2:beta 1 selectivity ratios. 3. Nadolol produced dose-related reductions in exercise tachycardia in keeping with increasing beta 1-adrenoceptor blockade; mean % reduction (95% CI) compared with placebo: N5 10.7 (6.6 to 14.8), N20 21.4 (17.3 to 25.4), N80 38.9 (34.8 to 42.9). However, even the lowest dose of nadolol (5 mg) produced almost complete blunting of beta 2-mediated effects and significantly increase exercise hyperkalaemia; peak exercise hyperkalaemia (mmol l-1) (means and 95% CI): PL 4.88 (4.68 to 5.07), N5 5.36 (5.17 to 5.55), N20 5.48 (5.28 to 5.67), N80 5.42 (5.22 to 5.61). beta 2:beta 1 selectivity ratios significantly increased as the dose of nadolol was reduced. 4. These data suggest that whereas in the clinical dose range nadolol behaves as a non-selective beta-adrenoceptor antagonist, as the dose is reduced this drug demonstrates an increasing degree of selectivity for the beta 2-adrenoceptor.(ABSTRACT TRUNCATED AT 250 WORDS)

  6. Pharmacokinetics of meloxicam after intravenous, intramuscular, and oral administration of a single dose to Hispaniolan Amazon parrots (Amazona ventralis).

    Science.gov (United States)

    Molter, Christine M; Court, Michael H; Cole, Gretchen A; Gagnon, David J; Hazarika, Suwagmani; Paul-Murphy, Joanne R

    2013-03-01

    To compare pharmacokinetics after IV, IM, and oral administration of a single dose of meloxicam to Hispaniolan Amazon parrots (Amazona ventralis). 11 healthy parrots. Cohorts of 8 of the 11 birds comprised 3 experimental groups for a crossover study. Pharmacokinetics were determined from plasma concentrations measured via high-performance liquid chromatography after IV, IM, and oral administration of meloxicam at a dose of 1 mg/kg. Initial mean ± SD plasma concentration of 17.3 ± 9.0 μg/mL was measured 5 minutes after IV administration, whereas peak mean concentration was 9.3 ± 1.8 μg/mL 15 minutes after IM administration. At 12 hours after administration, mean plasma concentrations for IV (3.7 ± 2.5 μg/mL) and IM (3.5 ± 2.2 μg/mL) administration were similar. Peak mean plasma concentration (3.5 ± 1.2 μg/mL) was detected 6 hours after oral administration. Absolute systemic bioavailability of meloxicam after IM administration was 100% but was lower after oral administration (range, 49% to 75%). Elimination half-lives after IV, IM, and oral administration were similar (15.9 ± 4.4 hours, 15.1 ± 7.7 hours, and 15.8 ± 8.6 hours, respectively). Pharmacokinetic data may provide useful information for use of meloxicam in Hispaniolan Amazon parrots. A mean plasma concentration of 3.5 μg/mL would be expected to provide analgesia in Hispaniolan Amazon parrots; however, individual variation may result in some birds having low plasma meloxicam concentrations after IV, IM, or oral administration. After oral administration, meloxicam concentration slowly reached the target plasma concentration, but that concentration was not sustained in most birds.

  7. Use of a monophasic, low dose oral contraceptive in relation to mental functioning

    NARCIS (Netherlands)

    Deijen, J.B.; Jansen, W.A.; Klitsie, J.; Duyn, K.

    1992-01-01

    The objective of the study was to evaluate the effect of Minulet, a new low-dose oral contraceptive on mood in two groups and to compare the effect with a control group of women not taking oral contraceptives (OC). The women participating were between 16 and 45 years of age. They completed the

  8. Oral dosing by voluntary  administration of jellybeans. Refinement and reduction of variability

    DEFF Research Database (Denmark)

    Pakula, Malgorzata Maria; Dagnæs-Hansen, Frederik

    2016-01-01

    Administration of substances by oral gavage is a common procedure in biomedical research involving laboratory animals, however although highly efficient, the procedure includes fixation of the animals and is technically challenging. Oral gavage is a precise way to dose animals, however it may ind...

  9. Occlusion-amblyopia following high dose oral levodopa combined with part time patching

    OpenAIRE

    Mihir Kothari

    2014-01-01

    Part time occlusion therapy is not reported to cause occlusion (reverse) amblyopia. However, when combined with high dose oral levodopa, an increase in the plasticity of the visual cortex can lead to occlusion amblyopia. In this case report, we describe a six year old child who developed occlusion amblyopia following part time patching combined with oral levodopa.

  10. Occlusion-amblyopia following high dose oral levodopa combined with part time patching.

    Science.gov (United States)

    Kothari, Mihir

    2014-12-01

    Part time occlusion therapy is not reported to cause occlusion (reverse) amblyopia. However, when combined with high dose oral levodopa, an increase in the plasticity of the visual cortex can lead to occlusion amblyopia. In this case report, we describe a six year old child who developed occlusion amblyopia following part time patching combined with oral levodopa.

  11. Occlusion-amblyopia following high dose oral levodopa combined with part time patching

    Directory of Open Access Journals (Sweden)

    Mihir Kothari

    2014-01-01

    Full Text Available Part time occlusion therapy is not reported to cause occlusion (reverse amblyopia. However, when combined with high dose oral levodopa, an increase in the plasticity of the visual cortex can lead to occlusion amblyopia. In this case report, we describe a six year old child who developed occlusion amblyopia following part time patching combined with oral levodopa.

  12. Control de la calidad y estudio de estabilidad del paracetamol gotas orales 100 mg/ml

    Directory of Open Access Journals (Sweden)

    Caridad M García Peña

    2013-03-01

    Full Text Available Introducción: las gotas orales de Paracetamol, están indicadas a la población infantil hasta los 5 años para el alivio de la fiebre, dolor de cabeza, dolores dentales y proporciona alivio sintomático del resfriado común. Objetivo: validar dos métodos analíticos, para el control de la calidad y el estudio de estabilidad y estudiar la estabilidad de las gotas orales de producción nacional. Métodos: para cuantificar el principio activo para el estudio de estabilidad, la separación se realizó a través de una columna cromatográfica Lichrosorb RP - 18 (5µm (250 x 4 mm, con detección ultravioleta a 243 nm, empleando una fase móvil compuesta por Agua destilada: Metanol (3:1. Mientras que el método para el control de la calidad se utilizó un Espectrofotómetro SPECTRONIC GENESYS 2.Para el estudio de estabilidad, se emplearon los métodos de vida de estante (a temperatura inferior a 30 º C y de estabilidad acelerada (40 ± 2ºC mediante cromatografía líquida de alta eficiencia. Resultados: los resultados obtenidos de los parámetros evaluados en las validaciones se encontraron dentro de los límites establecidos. Los resultados del estudio de estabilidad realizado, demuestran que el producto terminado cumplió con las especificaciones de calidad durante el estudio. Conclusiones: los métodos analíticos por espectrofotometría UV y cromatografía líquida de alta resolución, son válidos para el control de la calidad y estudio de estabilidad de las gotas orales de Paracetamol 100 mg/mL, ya que resultaron lineales, precisos, exactos y específicos. Se demostró la estabilidad física, química y microbiológica del producto por espacio de 12 meses a temperatura inferior a 30 ºC, envasados en frascos de vidrio ámbar por 15 mL, boca 18 mm, calidad hidrolítica III. Además se evidenció que el producto es estable durante 30 días después de abierto el frasco.

  13. Single-dose pharmacokinetics and tolerability of oral delta-9- tetrahydrocannabinol in patients with amyotrophic lateral sclerosis.

    Science.gov (United States)

    Joerger, Markus; Wilkins, Justin; Fagagnini, Stefania; Baldinger, Reto; Brenneisen, Rudolf; Schneider, Ursula; Goldman, Bea; Weber, Markus

    2012-06-01

    Cannabinoids exert neuroprotective and symptomatic effects in amyotrophic lateral sclerosis (ALS). We assessed the pharmacokinetics (PK) and tolerability of delta-9-tetrahydrocannabinol (THC) in ALS patients. Nine patients received THC single oral doses of 5mg and 10mg, separated by a wash-out period of two weeks. Blood samples for the determination of THC, 11-nor-9-carboxy-THC (THC-COOH) and hydroxy-THC (THC-OH) were taken up to 8 hours after intake. Adverse events were assessed by visual analogue scales (VAS). Plasma concentrations of the active metabolite THC-OH were submitted to sequential pharmacokinetic-pharmacodynamic population modeling on individual heart rate as a proxy for THC's cardiovasculatory effects. Drowsiness, euphoria, orthostasis, sleepiness, vertigo and weakness were significantly more frequent in patients receiving 10mg compared to 5 mg THC. A marked interindividual variability was found for the absorption of oral THC (84%) and elimination of THC-COOH (45%). PK data did not support any clinically relevant deviation from linear PK in the investigated range of concentrations. Plasma concentrations of THC-OH were positively correlated with the individual heart rate. An E(max-model) was successfully fitted to individual heart rate, with a THC-OH plasma concentration of 3.2 x 10(-4) μmol/L for EC(50) and an E(max) of 93 bpm for heart rate. The higher 10mg dose of THC was dose-limiting in patients with ALS. High interindividual PK variability requires individuell titration of THC for potential therapeutic use in patients with ALS.

  14. Pharmacokinetics of Levetiracetam in Healthy Hispaniolan Amazon Parrots ( Amazona ventralis ) After Oral Administration of a Single Dose.

    Science.gov (United States)

    Schnellbacher, Rodney; Beaufrère, Hugues; Vet, Dr Med; Arnold, Robert D; Tully, Thomas N; Mayer, Joerg; Divers, Stephen J

    2014-09-01

    Long-term anticonvulsive treatments have been poorly described in birds, and few pharmacokinetic studies have been performed, with mixed results. Levetiracetam, a new anticonvulsive drug, has shown good efficacy for monotherapy or adjunctive treatment of seizures in both human and veterinary medicine. To determine pharmacokinetics of levetiracetam in Hispaniolan Amazon parrots ( Amazona ventralis ), 20 healthy birds were randomly divided into 2 groups and administered either a 50 mg/kg (n = 10) or a 100 mg/kg (n = 10) oral dose of levetiracetam with no observable adverse effects. Blood samples were collected at baseline and at 12 time intervals (6 per group) for 16 hours. The concentration-time profiles resembled characteristic absorption, with maximum plasma concentrations of 61.0 μg/mL and 95.1 μg/mL at 60 minutes; terminal half-lives at 2.38 and 2.37 hours; volumes of distribution of 0.807 and 0.773 L/kg, with an area under the curve at 14 100 and 28 820 mg × min/L; and clearance rates of 3.65 and 3.60 mL/min per kg, respectively. Plasma concentrations were greater than 5.5 mg/L for up to 9.4 and 12 hours, suggesting an 8- and 12-hour oral dosing at 50 and 100 mg/kg, respectively, would be sufficient to maintain targeted values. Clinically, doses and frequencies may need escalation based on differences in species and individuals, and drug levels should be monitored.

  15. Alteration of the systemic and microcirculation by a single oral dose of flavan-3-ols.

    Directory of Open Access Journals (Sweden)

    Kodai Ingawa

    Full Text Available Several systematic reviews have reported that flow mediated dilatation (FMD was significantly increased in subjects after ingestion of chocolate that contains flavan-3-ols; however, the mechanisms responsible for this effect are not clear. In this study, we evaluated the effects of a single oral dose of flavan-3-ols on the systemic circulation and microcirculation in the cremaster muscle using intravital video microscopy in vivo. The cremaster muscle in rats was spread over a plastic chamber and a gastric tube was placed into the stomach. Blood flow in the cremasteric artery was determined using a laser Doppler flowmeter, while blood pressure and heart rate were measured by the tail-cuff method. Red blood cell velocity in arterioles and blood flow in the artery were significantly increased 5 min after the administration of 10 mg/kg flavan-3-ols compared with distilled water treatment. The number of capillaries recruited in the cremaster muscle was also significantly increased 15 min after treatment. Microscopic observation confirmed that increased shear stress on endothelial cells was maintained during the measurement period. The mean arterial blood pressure and heart rate were also significantly elevated soon after administration and returned to baseline before the end of the observation period. Plasma nitrate and nitrite levels, and NO phosphorylation of aortic tissue were significantly increased at 60 min after administration of flavan-3-ols. According to these results, a single oral dose of flavan-3-ols elevates blood pressure and flow transiently, and these effects induce NO production through increased shear stress on endothelial cells.

  16. An open-label, prospective interventional study of the tolerability and efficacy of 0.4 mg oral tamsulosin oral controlled absorption system in men with lower urinary tract symptoms associated with benign prostatic hyperplasia who are unsatisfied with treatment with 0.2 mg tamsulosin.

    Science.gov (United States)

    Yang, Pei-Shan; Chen, Chien-Lun; Hou, Chen-Pang; Lin, Yu-Hsiang; Tsui, Ke-Hung

    2018-01-01

    The aim of this study was to investigate the efficacy and tolerability of switching from 0.2 mg tamsulosin to 0.4 mg tamsulosin oral controlled absorption system (OCAS) over a 12-week period in Taiwanese men with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). Taiwanese male patients who were dissatisfied with treatment with 0.2 mg tamsulosin were enrolled in this clinical study and switched to 0.4 mg tamsulosin OCAS. Efficacy was assessed over a 12-week period by an International Prostate Symptom Score (IPSS) questionnaire and analysis of urinary flow by uroflowmetry. A statistically significant improvement was observed in total IPSS scores from baseline (14.94±7.41, moderate) to 12 weeks (7.36±5.77, mild) in 81 patients who were switched from 0.2 to 0.4 mg tamsulosin OCAS ( P tamsulosin OCAS dose was well tolerated, with only mild dizziness (five patients) and headache (two patients) as the most frequent adverse events. No clinically significant reduction was observed in blood pressure or vital signs. Treatment with 0.4 mg tamsulosin OCAS in Taiwanese men with LUTS associated with BPH who were dissatisfied with 0.2 mg tamsulosin significantly improved IPSS scores, urinary flow, and QOL and was well tolerated, suggesting that this should be the recommended dose offered to Taiwanese male patients.

  17. Oral High-Dose Multivitamins and Minerals or Post Myocardial Infarction Patients in TACT

    Science.gov (United States)

    Lamas, Gervasio A.; Boineau, Robin; Goertz, Christine; Mark, Daniel B.; Rosenberg, Yves; Stylianou, Mario; Rozema, Theodore; Nahin, Richard L.; Lindblad, Lauren; Lewis, Eldrin F.; Drisko, Jeanne; Lee, Kerry L.

    2014-01-01

    Background Oral multivitamins and minerals are often used in conjunction with ethylenediamine tetra acetic acid infusions to treat atherosclerotic disease. Whether high-dose multivitamins are effective as secondary prevention of atherosclerotic disease, however, has not been established. Objective The vitamin component of the Trial to Assess Chelation Therapy assessed whether oral multivitamins reduced cardiovascular events, and were safe. Design The Trial to Assess Chelation Therapy was designed as a double-blind placebo-controlled 2×2 factorial multicenter randomized trial. Setting 134 US and Canadian academic and clinical sites participated. Patients 1708 patients, age ≥50 years, ≥6 weeks post myocardial infarction, with creatinine level ≤ 176.8 µmol/L (2.0 mg/dL). (ClinicalTrials.gov: NCT00044213). Intervention Patients were randomly assigned to an oral 28-component high-dose multivitamin and multimineral mixture or placebo. Measurements Study results were analyzed per randomized group. The primary endpoint was time to total mortality, recurrent myocardial infarction, stroke, coronary revascularization, or hospitalization for angina. Limited secondary endpoints and subgroup analyses were also pre-specified. Results The median age was 65 years, 18% female. The qualifying myocardial infarction had occurred 4.6 (1.6, 9.2) years prior to enrollment. The median duration of follow-up was 55 months (IQR 26, 60) overall. The median number of months during which patients took their vitamins was 31 (13, 59) in the active treatment group, and 35 (13, 60) in the placebo group (p=0.65). There were 645 (76%) vitamin patients and 646 (76%) placebo patients who completed at least 1 year of oral therapy (p=0.98); and 400 (46.9%) vitamin patients and 426 (49.8%) placebo patients who completed at least 3 years of oral therapy (p=0.23). There were 783 (46%) of patients who discontinued their vitamin regimen (390 (46%) in placebo, 394 (46%) in active; p=0.67), and 17% of

  18. Tissue distribution and elimination of BDE 47 in mice following a single oral dose

    Energy Technology Data Exchange (ETDEWEB)

    Staskal, D. [Curriculum in Toxicology, Chapel Hill, NC (United States); Diliberto, J.; DeVito, M.; Birnbaum, L. [US EPA, ORD, NHEERL, ETD, RTP (United States)

    2004-09-15

    2,2',4,4'-Tetrabromodiphenyl ether (BDE 47) is a polybrominated diphenyl ether (PBDE) congener which is part of a class of brominated flame retardants (BFRs) commonly used in a variety of highly flammable consumer goods. Concern for the effects of PBDEs has increased significantly in recent years as their presence has been detected in environmental samples and in human tissues at steadily increasing concentrations. Despite its small contribution to the PBDE global production and usage, BDE 47 is the major congener found in environmental samples and human tissue. Limited toxicology studies suggest that BDE 47 is a developmental neurotoxicant and an endocrine disruptor however, several data gaps exist and must be investigated in order to evaluate the human health risk of BDE 47. This study investigated basic toxicokinetic properties of BDE 47 in female C57BL/6J mice. Here we report the effect of time on the absorption, distribution, and excretion following a single, oral dose of 14C-labeled BDE 47. Animals were administered 1.0mg BDE 47/kg bw, a dose chosen based on previous studies. Distribution and elimination were monitored at several time points ranging from 1 hour to 21 days following exposure. Data from these basic toxicokinetic studies will be applied to studies investigating the toxicokinetics of BDE 47 in a developmental model as well as in the development of a physiologically-based pharmacokinetic (PBPK) model.

  19. Concentrations of levofloxacin (HR 355) in the respiratory tract following a single oral dose in patients undergoing fibre-optic bronchoscopy.

    Science.gov (United States)

    Andrews, J M; Honeybourne, D; Jevons, G; Brenwald, N P; Cunningham, B; Wise, R

    1997-10-01

    Concentrations of levofloxacin were measured in bronchial biopsies, alveolar macrophages (AM), epithelial lining fluid (ELF) and serum following a single oral dose. Concentrations were measured by a microbiological assay method. A total of 35 patients undergoing fibre-optic bronchoscopy were studied. Mean serum, AM, ELF and biopsy concentrations were as follows. 0.5 h: 4.73 mg/L, 19.1 mg/L, 4.74 mg/L and 4.3 mg/kg; 1 h: 6.6 mg/L, 32.5 mg/L, 10.8 mg/L and 8.3 mg/kg; 2 h: 4.9 mg/L, 41.9 mg/L, 9.0 mg/L and 6.5 mg/kg; 4 h: 4.1 mg/L, 27.7 mg/L, 10.9 mg/L and 6.0 mg/kg; and 6-8 h: 4.0 mg/L, 38.4 mg/L, 9.6 mg/L and 4.0 mg/kg respectively. Mean serum and AM concentrations at 12-24 h were 1.2 and 13.9 mg/L respectively (concentrations in biopsy and ELF were only measurable in three of the six patients). These concentrations exceed the MIC90s of the common respiratory pathogens, Haemophilus influenzae (0.015 mg/L), Moraxella catarrhalis (0.06 mg/L) and Streptococcus pneumoniae (1 mg/L) and suggest that levofloxacin should be efficacious in the treatment of community- and hospital-acquired respiratory infection.

  20. Comparative assessment of efficacy of two different pretreatment single oral doses of betamethasone on inter-appointment and postoperative discomfort: An in vivo clinical evaluation.

    Science.gov (United States)

    Gyanani, Hitesh; Chhabra, Naveen; Parmar, Ghanshyam R

    2016-01-01

    Study aimed to evaluate the efficacy of two different pretreatment single oral doses of betamethasone on the incidence of inter-appointment flare up and postoperative discomfort. Fifty-four patients aged 18-59 years requiring endodontic treatment were selected and randomly assigned to three groups; single pretreatment oral dose of placebo or betamethasone in two different oral doses of 0.5 mg and 1 mg, respectively. Endodontic therapy was completed in two visits using triple antibiotic paste as intracanal medicament. Patients were given a questionnaire to record their pain at 1, 2, 3, and 7 days after treatment. In the second visit, obturation was done, and the patients were again instructed to record their pain scores after treatment and discharged. The verbal rating scale was used for recording the pain scores. Statistical analysis was done using ANOVA and the Friedman test. 0.5 mg betamethasone group showed least mean pain scores among all experimental groups; however, there was no statistically significant difference between any of the groups ( P > 0.05). Pretreatment single oral dose of betamethasone is an effective in managing endodontic flare-ups; however, the results were statistically insignificant.

  1. Intraocular levels of methotrexate after oral low-dose treatment in chronic uveitis.

    Science.gov (United States)

    Puchta, Joachim; Hattenbach, Lars-Olof; Baatz, Holger

    2005-01-01

    To determine the intraocular levels of methotrexate in low-dose treatment of noninfectious uveitis. One day after oral administration, the methotrexate level was measured in the aqueous humor and serum of a patient with noninfectious uveitis, who underwent cataract surgery. A fluorescence polarization immunoassay was used for determination. After oral administration, methotrexate was only measurable in aqueous humor but not in serum. In uveitis, orally administered low-dose methotrexate reaches detectable levels in aqueous humor, even in the absence of detectable levels in serum. Copyright (c) 2005 S. Karger AG, Basel.

  2. Plasma concentrations of fenbendazole (FBZ and oxfendazole in alpacas (Lama pacos after single intravenous and oral dosing of FBZ

    Directory of Open Access Journals (Sweden)

    Lakritz J

    2015-02-01

    Full Text Available Jeffrey Lakritz,1 Daniel Linden,2 David E Anderson,3 Terri A Specht4 1Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, USA; 2Department of Agriculture and Engineering Technologies, College of Food, Agriculture and Environmental Sciences, The Ohio State University, Wooster, OH, USA; 3Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN, USA; 4Four Star Veterinary Service, Chickasaw, OH, USA Abstract: The objective of this study was to determine plasma pharmacokinetics and bioavailability of fenbendazole (FBZ and oxfendazole (OFZ after intravenous (iv and oral administrations of FBZ (5 mg/kg to alpacas. Plasma concentrations of FBZ and OFZ after administration of FBZ iv and orally (5 mg/kg were determined by high-performance liquid chromatography with ultraviolet detection. Total clearance (CL of FBZ was 16.5±4 mL/kg/min (range: 4–31 mL/kg/min, and steady-state volume of distribution (Vdss was 3.3±1 L/kg (range: 1.7–7.4 L/kg. The terminal phase half-life of FBZ after iv administration was 5.9±3.8 hours (range: 0.8–20 hours. After oral administration, the FBZ terminal phase half-life was 23±5 hours (range: 9–37 hours and the systemic bioavailability of FBZ was 16%±6% (range: 1%–41%. Peak FBZ concentrations after oral administration were 0.13±0.05 µg/mL (range: 0.05–0.28 µg/mL at 10 hours (range: 8–12 hours. Peak plasma OFZ concentrations after oral dosing with FBZ (5 mg/kg were 0.14±0.05 µg/mL (0.05–0.3 µg/mL at 24±7 hours (range: 12–48 hours. FBZ clearance is lower in comparison to that of other species. Systemic availability of FBZ after oral administration is low after oral dosing. Metabolites of FBZ produced by alpacas are similar to those observed in other species. Keywords: bioavailability, benzimidazoles, camelid, pharmacokinetics

  3. Interference of intrinsic UV response of LiF:Mg,Ti (Poland) pellets in dose reassessment

    International Nuclear Information System (INIS)

    Bhasin, B.D.; Kalyane, G.N.; Kathuria, S.P.; Sunta, C.M.

    1987-01-01

    The thermoluminescence (TL) behaviour of sintered pellets of LiF:Mg,Ti (Poland) (LiF(P)) is markedly different from that of LiF:Mg,Ti TLD-100 (Harshaw) phosphor as far as their intrinsic responses to ultraviolet (UV) (253.7 nm) radiation are concerned. The intrinsic response of LiF(P) phosphor is very much dependent on the physical form of the phosphor. In addition, it is highly sensitive to any changes in experimental conditions such as the nature of the atmosphere during readout, the pre-heat and the readout history of the phosphor. The high intrinsic UV response (IUVR) of LiF(P) interferes in the dose reassessment by the PTTL (photo-transferred thermoluminescence) technique. Nevertheless, a fortuitous situation exists wherein a PTTL dosimetry peak signal is seen clearly over-riding the IUVR valley at the corresponding point of the glow curve. A procedure to correct for the IUVR interference and to re-estimate the dose by the PTTL technique is described. (author)

  4. Effect of beam arrangement on oral cavity dose in external beam radiotherapy of nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Wu, Vincent W.C.; Yang Zhining; Zhang Wuzhe; Wu Lili; Lin Zhixiong

    2012-01-01

    This study compared the oral cavity dose between the routine 7-beam intensity-modulated radiotherapy (IMRT) beam arrangement and 2 other 7-beam IMRT with the conventional radiotherapy beam arrangements in the treatment of nasopharyngeal carcinoma (NPC). Ten NPC patients treated by the 7-beam routine IMRT technique (IMRT-7R) between April 2009 and June 2009 were recruited. Using the same computed tomography data, target information, and dose constraints for all the contoured structures, 2 IMRT plans with alternative beam arrangements (IMRT-7M and IMRT-7P) by avoiding the anterior facial beam and 1 conventional radiotherapy plan (CONRT) were computed using the Pinnacle treatment planning system. Dose-volume histograms were generated for the planning target volumes (PTVs) and oral cavity from which the dose parameters and the conformity index of the PTV were recorded for dosimetric comparisons among the plans with different beam arrangements. The dose distributions to the PTVs were similar among the 3 IMRT beam arrangements, whereas the differences were significant between IMRT-7R and CONRT plans. For the oral cavity dose, the 3 IMRT beam arrangements did not show significant difference. Compared with IMRT-7R, CONRT plan showed a significantly lower mean dose, V30 and V-40, whereas the V-60 was significantly higher. The 2 suggested alternative beam arrangements did not significantly reduce the oral cavity dose. The impact of varying the beam angles in IMRT of NPC did not give noticeable effect on the target and oral cavity. Compared with IMRT, the 2-D conventional radiotherapy irradiated a greater high-dose volume in the oral cavity.

  5. Nonrandomized study comparing the effects of preoperative radiotherapy and daily administration of low-dose cisplatin with those radiotherapy alone for oral cancer

    International Nuclear Information System (INIS)

    Kurita, Hiroshi; Azegami, Takuya; Kobayashi, Hirokazu; Kurashina, Kenji; Tanaka, Kouichi; Kotani, Akira; Oguchi, Masahiko; Tamura, Minoru.

    1997-01-01

    The purpose of this study was to compare the effect of preoperative radiotherapy and daily administration of low-dose cisplatin with those of radiotherapy alone for oral cancer. Ten patients underwent preoperative radiotherapy of 30 to 40 Gy with concomitant daily administration of low-dose cisplatin (5 mg/body or 5 mg/m 2 ). Ten patients received external radiotherapy alone. The locoregional response rates (complete response and partial response) did not differ significantly between the two groups (80% for combined therapy and 60% for radiotherapy alone). On histopathologic evaluation of surgical specimens, however, the combined-therapy group (80%) had a higher response rate than did the radiotherapy-alone group (10%; p<0.01). We conclude that daily administration of low-dose cisplatin enhances the efficacy of radiotherapy against primary tumors. We also suggested that combined therapy may be beneficial as an initial treatment for oral cancer before a planned operation. (author)

  6. The effect of pycnogenol on patients with dysmenorrhea using low-dose oral contraceptives

    Directory of Open Access Journals (Sweden)

    Maia Jr H

    2014-12-01

    Full Text Available Hugo Maia Jr, Clarice Haddad, Julio Casoy Centro de Pesquisa e Assistência em Reprodução Humana (CEPARH, Salvador, Bahia, BrazilObjective: Menstrual symptoms such as dysmenorrhea usually occur during the hormone-free interval in oral contraceptive users. Progestin withdrawal activates NF-κB transcription factor, which upregulates both vascular endothelial growth factor (VEGF and Cox-2 expression in the endometrium. The use of natural NF-κB inhibitors such as pycnogenol may block this response, improving dysmenorrhea.Patients and methods: Twenty-four patients with severe dysmenorrhea were allocated to one of two treatment groups. In Group A (n=13, women were treated with an oral contraceptive containing 15 µg of ethinyl estradiol and 60 mg of gestodene (Adoless® in a 24/4 regimen for three consecutive cycles. Women in Group B (n=11 used the same contraceptive regimen together with 100 mg of pycnogenol (Flebon® continuously for 3 months. Pain scores were graded using a visual analog scale (VAS before and during the hormone-free interval at the end of the third treatment cycle.Results: Before treatment, VAS pain scores for dysmenorrhea were 8 and 9 in Groups A and B, respectively. However, by the end of the third treatment cycle, pain scores had decreased significantly (P<0.05 both in groups A and B. The final pain scores were 6 in Group A and 2 in Group B, a difference that was statistically significant (P<0.0001. In Group B, 27% of the patients became pain-free, while in Group A, none of the women reported complete disappearance of this symptom. The number of bleeding days was also lower in Group B.Discussion: Pycnogenol effectively decreased pain scores and the number of bleeding days when administered concomitantly with a low-dose 24/4 oral contraceptive containing gestodene.Keywords: gestodene, hormone-free interval, pain

  7. Pharmacokinetics of repeated oral doses of amlodipine and amlodipine plus telmisartan in healthy volunteers.

    Science.gov (United States)

    Stangier, J; Su, C A

    2000-12-01

    This open-label, crossover study was performed to establish if there is evidence for interaction between telmisartan, an angiotensin II antagonist, and amlodipine, a class II (dihydropyridine) calcium channel antagonist, on the basis of pharmacokinetics and safety. In a two-way crossover trial, 12 healthy Caucasian males were randomized to receive once daily for 9 days oral amlodipine 10 mg with or without oral telmisartan 120 mg. After a washout period of > or = 13 days, the subjects were switched to the other medication regimen. The geometric means of the primary pharmacokinetic parameters at steady state (day 9) for amlodipine when given alone were the following: maximum plasma concentration (Cmax) 17.7 ng/mL, area under the plasma concentration-time curve (AUC) 331 ng.h/mL, and renal clearance 39.5 mL/min, with 8% of the total amlodipine dose being excreted. When concomitant telmisartan was given, the respective values were 18.7 ng/mL, 352 ng.h/mL, and 43.0 mL/min, with 9.4% of the total amlodipine dose being excreted renally. The limits of the 90% confidence intervals (CIs) for the ratios of these steady-state parameters were 0.97 to 1.14 for Cmax and 0.98 to 1.16 for AUC; both were within the predefined reference range (0.8 to 1.25) for bioequivalence. The high intersubject variability in urinary amlodipine excretion resulted in bioequivalence not being demonstrated for renal clearance. Adverse effects were few, mild to moderate in intensity, and transient whether amlodipine was given alone or with telmisartan. Vital signs, except for blood pressure, and clinical laboratory values were unaffected by either medication. The findings of this study show that concomitant telmisartan and amlodipine may be administered as there is no clinically significant variation in primary pharmacokinetic parameters of amlodipine in the presence of telmisartan, and the safety of the combination is comparable to that of amlodipine alone.

  8. A New Orally Active, Aminothiol Radioprotector-Free of Nausea and Hypotension Side Effects at Its Highest Radioprotective Doses

    Energy Technology Data Exchange (ETDEWEB)

    Soref, Cheryl M. [ProCertus BioPharm, Inc., Madison, WI (United States); Hacker, Timothy A. [Department of Medicine, Cardiovascular Physiology Core, University of Wisconsin-Madison, Madison, WI (United States); Fahl, William E., E-mail: fahl@oncology.wisc.edu [ProCertus BioPharm, Inc., Madison, WI (United States); McArdle Laboratory for Cancer Research, University of Wisconsin Carbone Cancer Center, Madison, WI (United States)

    2012-04-01

    Purpose: A new aminothiol, PrC-210, was tested for orally conferred radioprotection (rats, mice; 9.0 Gy whole-body, which was otherwise lethal to 100% of the animals) and presence of the debilitating side effects (nausea/vomiting, hypotension/fainting) that restrict use of the current aminothiol, amifostine (Ethyol, WR-2721). Methods and Materials: PrC-210 in water was administered to rats and mice at times before irradiation, and percent-survival was recorded for 60 days. Subcutaneous (SC) amifostine (positive control) or SC PrC-210 was administered to ferrets (Mustela putorius furo) and retching/emesis responses were recorded. Intraperitoneal amifostine (positive control) or PrC-210 was administered to arterial cannulated rats to score drug-induced hypotension. Results: Oral PrC-210 conferred 100% survival in rat and mouse models against an otherwise 100% lethal whole-body radiation dose (9.0 Gy). Oral PrC-210, administered by gavage 30-90 min before irradiation, conferred a broad window of radioprotection. The comparison of PrC-210 and amifostine side effects was striking because there was no retching or emesis in 10 ferrets treated with PrC-210 and no induced hypotension in arterial cannulated rats treated with PrC-210. The tested PrC-210 doses were the ferret and rat equivalent doses of the 0.5 maximum tolerated dose (MTD) PrC-210 dose in mice. The human equivalent of this mouse 0.5 MTD PrC-210 dose would likely be the highest PrC-210 dose used in humans. By comparison, the mouse 0.5 MTD amifostine dose, 400 {mu}g/g body weight (equivalent to the human amifostine dose of 910 mg/m{sup 2}), when tested at equivalent ferret and rat doses in the above models produced 100% retching/vomiting in ferrets and 100% incidence of significant, progressive hypotension in rats. Conclusions: The PrC-210 aminothiol, with no detectable nausea/vomiting or hypotension side effects in these preclinical models, is a logical candidate for human drug development to use in healthy

  9. Efficacy of the low-dose combined oral contraceptive chlormadinone acetate/ethinylestradiol: physical and emotional benefits.

    Science.gov (United States)

    Heskamp, Marie-Luise S; Schramm, Georg A K

    2010-01-01

    This study investigated the effects of the low-dose combined oral contraceptive (COC) 2.0 mg chlormadinone acetate (CMA)/0.03 mg ethinylestradiol (EE) (Belara, Balanca) on cycle-related physical and emotional disorders in women >or=25 years of age. A prospective, non-interventional, observational study of 3772 women over six cycles was conducted in 303 office-based gynecological centers throughout Germany. CMA/EE provided high contraceptive efficacy with a Pearl index of 0 (95% confidence interval=0.00-0.22) and was generally well tolerated, with no statistically significant weight changes during the observation period (p=.147). CMA/EE intake resulted in a statistically significant improvement in cycle-related physical and emotional symptoms, with a 67% overall reduction in sum score for number and intensity of cycle-related symptoms per patient. The results of this study in women >or=25 years of age support previous findings that 2.0 mg CMA/0.03 mg EE is an effective low-dose COC, with an excellent tolerability profile, with the additional benefits of significantly reducing both cycle-related physical and emotional symptoms (pcontraceptive treatment. Further research is warranted.

  10. Placental and milk transfer, disposition and elimination of a single oral dose of [14C acetyl] acephate in Sprague Dawley rats

    International Nuclear Information System (INIS)

    Bakry, N.M.; Salama, A.K.; Abou-Donia, M.B.

    1991-01-01

    A single oral dose of 40 mg/kg (6.4 μCi/kg) of [ 14 C acetyl]acephate was administered on day 18 of gestation to pregnant Sprague Dawley rats. Eight groups of three rats were killed after 10 min and 0.5, 1, 3, 6, 12, 24, and 48 hr. At the end of the 48 hr experimental period, a total of 22.38% of the dose was exhaled as carbon dioxide, while only 1.25% and 0.60% of the dose were eliminated in the urine and feces, respectively. Trace amount (0.03% of the dose) was recovered in expired air as volatile materials. Radioactive acephate was rapidly absorbed and distributed in the tissues, with levels in most tissues reaching a peak concentration within 1 to 3 hr. The highest concentration of radioactivity was present in the maternal stomach followed by the liver. A total of 0.72% of the dose was recovered in the fetus. In another study, a single oral dose of 40 mg/kg [ 14 C acetyl]acephate was administered to the dams right after delivery. Nursing and suckling groups were killed at intervals of 1, 3, 6, 12, 24, 36, and 48 hr after dosing. Generally, the highest concentrations of radioactivity were present in the stomach, small intestine, liver, lung, and kidneys. A total of 0.96% of the dose was recovered in the sucklings

  11. Actual use of and adherence to ibuprofen 400 mg tablet dosing instructions in a simulated OTC environment
.

    Science.gov (United States)

    Meeves, Suzanne; Leyva, Rina; Richardson, Clark; Wilson, Brenda; Savastano, David M

    2017-07-01

    Evaluate adherence of US consumers to proposed label directions for a new 400 mg ibuprofen formulation. In this single-arm, open-label, multicenter, 30-day study simulating an over-the-counter (OTC)-like environment, US analgesic consumers reviewed proposed product packaging for a new 400 mg ibuprofen formulation and made a purchase decision. Purchasers used the product as needed and recorded use over 30 days. Outcomes included the percentage of participants who exhibited correct or acceptable product use for the primary endpoint (not exceeding 1,200 mg/day > 2 times during the study) or secondary endpoint (not exceeding 400 mg/dose > 2 times during the study) and adherence to the labeled dosing interval of 6 - 8 hours. Primary endpoint success was met if the lower bound of the 95% confidence interval (CI) was ≥ 85%. Of 685 purchasers providing use data, correct or acceptable use behavior occurred in 95.2% (95% CI: 93.6%, 96.8%) regarding total daily dose and in 84.4% (95% CI: 81.7%, 87.1%) regarding the number of tablets taken per dosing occasion. Most participants (87.3%) never used > 1,200 mg/day or took > 1 tablet/dose (78.1%). Nearly 43% of subjects re-dosed within 6 hours of the previous dose; of these, ~ 82% re-dosed between the 4- and 6-hour time intervals. Adverse events were consistent with prior ibuprofen 200 mg experience. This study provides evidence that a majority of US consumers would be able to use OTC ibuprofen 400 mg tablets in a manner consistent with product labeling. Misuse rates were low and unlikely to generate an excess risk of clinically important adverse events.
.

  12. Practice of superselective intraarterial high-dose cisplatin chemoradiotherapy in the oral cavity

    International Nuclear Information System (INIS)

    Yoshida, Tomoyuki; Nakamura, Kazuhiro; Tsukahara, Kiyoaki; Inagaki, Taro; Ito, Hiroyuki; Shimizu, Akira; Takata, Daisuke; Okamoto, Isaku; Kondo, Takahito

    2011-01-01

    Superselective intraarterial infusion enables high-dose chemotherapeutic agents to be administered via tumor feeding vessels to neutralize and limit the adverse cisplatin effects acceptable. Between 1998 and 2008, we evaluated the efficacy of first-line therapy and adverse events in 30 subjects with oral squamous cell cancer undergoing simultaneous superselective intra arterial high-dose chemotherapy and radiotherapy. The 30 subjects- 23 men and 7 women aged 40 to 72- consisted of 3 T2, 12 T3, and 15 T4. Four patients had N0, 8 N1, 7 N2b, 8 N2c, and 3 N3 disease. Two were in CS II, 6 III, 17 IVa, and 5 IVb (III>93%, IV: 73%). Superselective intra arterial chemotherapy delivered through the femoral artery used the Seldinger technique. A single cisplatin dose of 100-550 mg/m 2 (mean 440 mg/m 2 ). Five minutes after intra arterial infusion, sodium thiosulphate (9 g/m 2 ) was administered via a peripheral cutaneous vein in the contralateral forearm. Concurrent radiotherapy started on Day 2 at 2 Gy per session for a total of 60 Gy. Two to 3 weeks later, 15 under went the second course of superselective intra arterial chemotherapy after tumor feeding vessels were visualized angiographically. Four (13.3%) subjects with Grade 3 or greater myelosuppression required granulocyte-colony stimulating factor (G-CSF). Grade 3 or greater mucositis was observed in 57% and Grade 4 mucositis occurred in 5 (16.7%). All adverse effects were reversible and no serious adverse events were prolonged. Among those responding to first-line therapy, 24 of the 30 (80%) achieved complete response (CR) and 6 (20%) partial response (PR), but no stable disease (SD) or no change (NC). Overall response was 100%. Histopathologically, 2 of 9 undergoing postchemoradiotherapy had no tumors. Clinical and pathological CR was 86.7%. Adverse events associated with this therapy associated events were considered relatively mild and within allowable limits. (author)

  13. Lenalidomide at the dose of 25 mg every other day in patients affected by multiple myeloma and renal failure: a real-life experience.

    Science.gov (United States)

    Cerchione, Claudio; Nappi, Davide; Pareto, Anna E; Romano, Alessandra; Martinelli, Vincenzo; Picardi, Marco; Pane, Fabrizio; Catalano, Lucio

    2018-04-01

    Renal impairment (RI) is a relevant complication of patients affected by multiple myeloma (MM); it can be present in up to 30-35% of newly diagnosed MM and is linked to a poor outcome. However, early recognition and early treatment with novel agents can overcome the negative impact of RI and even reverse kidney damage in most cases. Lenalidomide, available as an oral compound, is an immunomodulatory drug with both antiproliferative and immunomodulatory activity that is largely used in the management of MM. Dose reduction is mandatory in RI; however, there is no theoretical assumption against the possibility that protracting the time of full standard doses can be equally effective and tolerated by patients requiring reduced doses. In this report, we describe our retrospective experience, in 18 patients, with the administration of lenalidomide 25 mg every other day for patients with MM and RI. The overall response ratio was 66.5%. More than half (61.1%) of the patients had a renal response. The median progression-free survival was 8 months (range: 3-18 months). No serious adverse event occurred during treatment, and it was never necessary to disrupt or delay treatment for toxicity. These preliminary observations point to a significant therapeutic effect of lenalidomide, at the dose of 25 mg every other day for 21 days, with logistic and economic advantages. However, these results should be validated by controlled studies involving larger numbers of patients.

  14. The effects of age on the pharmacokinetics and pharmacodynamics of single oral doses of benazepril and enalapril.

    Science.gov (United States)

    Macdonald, N J; Sioufi, A; Howie, C A; Wade, J R; Elliott, H L

    1993-01-01

    1. Eighteen healthy, normotensive subjects (nine young and nine elderly) participated in a double-blind, 3-way, crossover study to compare aspects of the pharmacokinetics and pharmacodynamics of single oral doses of 10 mg benazepril, 10 mg enalapril and placebo. 2. The hypotensive effect was similar after both drugs but the absolute reductions were greater in the elderly who had higher initial levels of blood pressure. 3. The AUCs for both benazeprilat and enalaprilat were higher in the elderly but by a significantly greater amount for enalaprilat (+ 113% vs 40%; P benazepril are qualitatively similar to those with other ACE inhibitors. The clinical significance of the quantitative differences requires further investigation. PMID:9114905

  15. Repeated dose oral toxicity of inorganic mercury in wistar rats: biochemical and morphological alterations

    Directory of Open Access Journals (Sweden)

    M. D. Jegoda

    2013-06-01

    Full Text Available Aim: The study was conducted to find out the possible toxic effect of mercuric chloride (HgCl2 at the histological, biochemical, and haematological levels in the wistar rats for 28 days. Materials and Methods: The biochemical and hematological alteration were estimated in four groups of rat (each group contain ten animals, which were treated with 0 (control, 2, 4, and 8 mg/kg body weight of HgCl2 through oral gavage. At the end of study all rats were sacrificed and subjected for histopathology. Result: A significantly (P < 0.05 higher level of serum alanine amino transferase (ALT, gamma Glutamyle Transferase, and creatinine were recorded in treatment groups, while the level of alkaline phosphtase (ALP was significantly decreased as compared to the control group. The toxic effect on hematoclogical parameter was characterized by significant decrease in hemoglobin, packed cell volume, total erythrocytes count, and total leukocyte count. Gross morphological changes include congestion, severe haemorrhage, necrosis, degenerative changes in kidneys, depletion of lymphocyte in spleen, decrease in concentration of mature spermatocyte, and edema in testis. It was notable that kidney was the most affected organ. Conclusion: Mercuric chloride (HgCl caused dose-dependent toxic effects on blood parameters and kidney. [Vet World 2013; 6(8.000: 563-567

  16. A multicenter dose-escalation study of the analgesic and adverse effects of an oral cannabis extract (Cannador) for postoperative pain management.

    Science.gov (United States)

    Holdcroft, Anita; Maze, Mervyn; Doré, Caroline; Tebbs, Susan; Thompson, Simon

    2006-05-01

    Cannabinoids have dose-related antinociceptive effects in animals. This clinical study aimed to investigate whether a single oral dose of cannabis plant extract (Cannador; Institute for Clinical Research, IKF, Berlin, Germany) could provide pain relief with minimal side effects for postoperative pain. Patients (aged 18-75 yr) were recruited and consented before surgery if patient-controlled analgesia was planned for provision of postoperative pain relief. Each patient received a single dose of 5, 10, or 15 mg Cannador if he or she had at least moderate pain after stopping patient-controlled analgesia. Starting with 5 mg, dose escalation was based on the number of patients requesting rescue analgesia and adverse effects. Pain relief, pain intensity, and side effects were recorded over 6 h and analyzed using tests for trend with dose. Rescue analgesia was requested by all 11 patients (100%) receiving 5 mg, 15 of 30 patient (50%) receiving 10 mg, and 6 of 24 patients (25%) receiving 15 mg Cannador (log rank test for trend in time to rescue analgesia with dose P analgesics without frequent adverse effects.

  17. Validation of an analytical method applicable to study of 1 mg/mL oral Risperidone solution stability

    International Nuclear Information System (INIS)

    Abreu Alvarez, Maikel; Garcia Penna, Caridad Margarita; Martinez Miranda, Lissette

    2010-01-01

    A validated analytical method by high-performance liquid chromatography (HPLC) was applicable to study of 1 mg/mL Risperidone oral solution stability. The above method was linear, accurate, specific and exact. A stability study of the 1 mg/mL Risperidone oral solution was developed determining its expiry date. The shelf life study was conducted for 24 months at room temperature; whereas the accelerated stability study was conducted with product under influence of humidity and temperature; analysis was made during 3 months. Formula fulfilled the quality specifications described in Pharmacopeia. The results of stability according to shelf life after 24 months showed that the product maintains the parameters determining its quality during this time and in accelerated studies there was not significant degradation (p> 0.05) in the product. Under mentioned conditions expiry date was of 2 years

  18. High-dose superselective intra-arterial cisplatin and concomitant radiation therapy for carcinoma of the oral cavity

    International Nuclear Information System (INIS)

    Suzuki, Gen; Tanaka, Norimitsu; Ogo, Etuyo

    2007-01-01

    The purpose of this study was to evaluate the effect of high-dose superselective intra-arterial cisplatin and concomitant radiation therapy for carcinoma of the oral cavities. The subjects consisted of 18 patients with carcinoma of the oral, and cavity treated with superselective intra-arterial infusion of high dose cisplatin (100 mg/body) concomitant with delivery of external beam radiotherapy (median total dose, 60.8 Gy) between 2001 and 2004. Sodium thiosulfate was administered intravenously to provide effective cisplatin neutlization. They were International Union Against Cancer (UICC)1997 stage II-IV (stage II: 4 patients, stage III: 4 patients, stage IV: 10 patients). Patients ranged from 43-81 years of age, with a median of 60 years, and included 14 men and 4 women. A follow-up period was 6 months minimum from the atart of the radiation therapy, the median follow up period at 28 months. The three-year overall survival rate was 71%. The three-year disease free rate and local control rate were 60% and 65%, respectively. Three-year local control rate of the T2-3 was achieved at 83%, and that for T4 at 50%. There was borderline significant difference in local control rate between T2-3 and T4 (p=0.05). We conclude that the high-dose superselective intra-arterial cisplatin and concomitant radiation therapy provides effective results in organ preservation for cancer of oral cavities. Further studies are also required to determine the validity of this method. (author)

  19. Pharmacokinetic and pharmacogenomic profiles of telmisartan after the oral microdose and therapeutic dose.

    Science.gov (United States)

    Ieiri, Ichiro; Nishimura, Chisa; Maeda, Kazuya; Sasaki, Tomohiro; Kimura, Miyuki; Chiyoda, Takeshi; Hirota, Tekeshi; Irie, Shin; Shimizu, Hitoshi; Noguchi, Takanori; Yoshida, Kenji; Sugiyama, Yuichi

    2011-08-01

    In this study, we evaluated (a) the contribution of SLCO1B3 and UGT1A polymorphisms to the pharmacokinetics of telmisartan in two forms, a microdose (MD) and a therapeutic dose (TD); (b) linkage disequilibrium (LD) between UGT1A1 and UGT1A3; and (c) linearity in the pharmacokinetics of telmisartan between the two forms. Telmisartan was orally administered at MD condition (100 μg), and then at TD condition (80 mg) to 33 healthy volunteers whose genotypes were prescreened by DMET Plus. Plasma concentrations of telmisartan and its glucuronide were measured by LC-MS/MS, and population pharmacokinetic analysis was performed. No obvious effect of SLCO1B3 polymorphisms (334T>G, 699G>A, and rs11045585) on the pharmacokinetics of telmisartan was observed. The strong LD between UGT1A1*6 and UGT1A3*4a, and between UGT1A1*28 and UGT1A3*2a were observed. After both MD and TD administration, the mean area under the curve0-24 (±standard deviation) of telmisartan was significantly lower and higher in individuals with the UGT1A3*2a (TD, 1701±970 ng hr/ml; MD, 978±537 pg hr/ml) and *4a variants (TD, 5340±1168; MD, 3145±1093), respectively, compared with those in individuals with UGT1A3*1/*1 (TD, 2969±1456; MD, 1669±726). These results were quantitatively confirmed by population pharmacokinetic analysis. Nonlinearity of the dose-exposure relationship was observed between the MD and TD. The haplotypes of UGT1A3 significantly influenced pharmacokinetics of telmisartan and a strong LD between UGT1A1 genotype and UGT1A3 haplotype was observed. These findings are potentially of pharmacological and toxicological importance to the development and clinical use of drugs.

  20. Single-dose intravenous iron infusion or oral iron for treatment of fatigue after postpartum haemorrhage

    DEFF Research Database (Denmark)

    Holm, C; Thomsen, L L; Norgaard, A

    2017-01-01

    BACKGROUND AND OBJECTIVES: To evaluate the clinical efficacy of a single-dose intravenous infusion of iron isomaltoside compared with current treatment practice with oral iron measured by physical fatigue in women after postpartum haemorrhage. MATERIALS AND METHODS: Single-centre, open-label, ran......BACKGROUND AND OBJECTIVES: To evaluate the clinical efficacy of a single-dose intravenous infusion of iron isomaltoside compared with current treatment practice with oral iron measured by physical fatigue in women after postpartum haemorrhage. MATERIALS AND METHODS: Single-centre, open...

  1. Sevoflurane-emergence agitation: Effect of supplementary low-dose oral ketamine premedication in preschool children undergoing dental surgery

    Directory of Open Access Journals (Sweden)

    Khattab Ahmed

    2009-01-01

    Full Text Available Background and Objectives: The use of sevoflurane in pediatric anesthesia, which could enable a more rapid emergence and recovery, is complicated by the frequent occurrence of post-anesthesia agitation. This study aims to test the efficacy of adding a low dose of ketamine orally, as a supplement to the midazolam-based oral premedication for reducing sevoflurane-related emergence agitation. Materials and Methods: Ninety-two preschool children, aged between two and six years, with an American Society of Anesthesiologists physical status I or II, scheduled for elective dental filling and extractions under general anesthesia were included. The patients were allocated into two groups: Group M (46 patients received oral midazolam 0.5 mg/kg, mixed with ibuprofen 10 mg/kg, while group KM (46 patients received a similar premedication mixture, in addition to ketamine 2 mg/kg. The acceptance of the drug mixture, the onset of action, and the occurrence of vomiting were monitored over the next 30 minutes. Induction of anesthesia was carried out using sevoflurane 8 Vol% in 100% oxygen via face mask. Anesthesia was maintained with sevoflurane 1.5-2 Vol% in an oxygen-nitrous oxide mixture. After extubation, the standard scoring scale was used for assessing the quality of emergence. Agitation parameters were measured using a five-point scale. Agitated children were managed by giving intravenous increments of fentanyl 1 μg/ kg. The time of hospital discharge allowance was recorded. Results: Drug palatability, vomiting, and onset of action of premedication; showed no significant differences between both groups. Time of eye opening after discontinuation of sevoflurane showed no significant differences between both groups. Postoperative agitation score and rescue fentanyl consumption were higher in group M than in group KM on admission to the PACU ( P < 0.01. The time of hospital discharge allowance in group M was longer than in group KM ( P< 0.05. Conclusion

  2. Dose Measurements in a Phantom Simulating Neonates by Using Different TL Materials: LiF:Mg,Cu,P and LiF:Mg,Ti

    International Nuclear Information System (INIS)

    Saez-Vergara, J.C.; Romero, A.M.; Fernandez, C.; Gomez, S.; Vazquez, J.; Olivares, M.P.

    1999-01-01

    A study reproducing usual exposure conditions in a special care baby unit has been performed to measure doses using TL materials in a versatile phantom specially designed for neonates having X ray examinations. The phantom offers the possibilities of reproducing different patient thicknesses and representing either a solid or hollow lung region. The results of the dose measurements using TL materials at the entrance, exit and both laterals of the phantom during different chest radiograph conditions are presented. Test conditions were reproduced in both hollow and solid chest cages simulating patient thicknesses of 5, 6 and 7 cm. The study was completed using two types of TL materials, LiF:Mg,Cu,P and LiF:Mg,Ti, in order to analyse and correct the differences on energy response between the two phosphors. (author)

  3. Development of a Biomarker for Penconazole: A Human Oral Dosing Study and a Survey of UK Residents’ Exposure

    Directory of Open Access Journals (Sweden)

    Craig Sams

    2016-05-01

    Full Text Available Penconazole is a widely used fungicide in the UK; however, to date, there have been no peer-reviewed publications reporting human metabolism, excretion or biological monitoring data. The objectives of this study were to i develop a robust analytical method, ii determine biomarker levels in volunteers exposed to penconazole, and, finally, to iii measure the metabolites in samples collected as part of a large investigation of rural residents’ exposure. An LC-MS/MS method was developed for penconazole and two oxidative metabolites. Three volunteers received a single oral dose of 0.03 mg/kg body weight and timed urine samples were collected and analysed. The volunteer study demonstrated that both penconazole-OH and penconazole-COOH are excreted in humans following an oral dose and are viable biomarkers. Excretion is rapid with a half-life of less than four hours. Mean recovery of the administered dose was 47% (range 33%–54% in urine treated with glucuronidase to hydrolyse any conjugates. The results from the residents’ study showed that levels of penconazole-COOH in this population were low with >80% below the limit of detection. Future sampling strategies that include both end of exposure and next day urine samples, as well as contextual data about the route and time of exposure, are recommended.

  4. High dose rate versus low dose rate brachytherapy for oral cancer--a meta-analysis of clinical trials.

    Directory of Open Access Journals (Sweden)

    Zhenxing Liu

    Full Text Available To compare the efficacy and safety of high dose rate (HDR and low dose rate (LDR brachytherapy in treating early-stage oral cancer.A systematic search of MEDLINE, EMBASE and Cochrane Library databases, restricted to English language up to June 1, 2012, was performed to identify potentially relevant studies.Only randomized controlled trials (RCT and controlled trials that compared HDR to LDR brachytherapy in treatment of early-stage oral cancer (stages I, II and III were of interest.Two investigators independently extracted data from retrieved studies and controversies were solved by discussion. Meta-analysis was performed using RevMan 5.1. One RCT and five controlled trials (607 patients: 447 for LDR and 160 for HDR met the inclusion criteria. The odds ratio showed no statistically significant difference between LDR group and HDR group in terms of local recurrence (OR = 1.12, CI 95% 0.62-2.01, overall mortality (OR = 1.01, CI 95% 0.61-1.66 and Grade 3/4 complications (OR = 0.86, CI 95% 0.52-1.42.This meta-analysis indicated that HDR brachytherapy was a comparable alternative to LDR brachytherapy in treatment of oral cancer. HDR brachytherapy might become a routine choice for early-stage oral cancer in the future.

  5. Dose selection trial of metronomic oral vinorelbine monotherapy in patients with metastatic cancer: a hellenic cooperative oncology group clinical translational study

    International Nuclear Information System (INIS)

    Briasoulis, Evangelos; Vassias, Antonios; Klouvas, George; Boukovinas, Ioannis; Fountzilas, George; Syrigos, Kostantinos N; Kalofonos, Haralambos; Samantas, Epaminontas; Aravantinos, Gerasimos; Kouvatseas, George; Pappas, Periklis; Biziota, Eirini; Sainis, Ioannis; Makatsoris, Thomas; Varthalitis, Ioannis; Xanthakis, Ioannis

    2013-01-01

    Metronomic chemotherapy is considered an anti-angiogenic therapy that involves chronic administration of low-dose chemotherapy at regular short intervals. We investigated the optimal metronomic dose of oral vinorelbine when given as monotherapy in patients with metastatic cancer. Patients with recurrent metastatic breast (BC), prostate (PC) or non-small cell lung cancer (NSCLC) and adequate organ functions were randomly assigned to 30, 40 or 50 mg vinorelbine, taken orally three times a week. Treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or maximum 24 months. Primary endpoint was time-to-treatment failure (TTF) and secondary were progression-free survival (PFS), toxicity, changes in blood concentrations of angiogenesis-associated biomarkers and pharmacokinetics. Seventy-three patients were enrolled. Four-month TTF rate did not differ between the three arms: 25.9% (11.1%-46.2% 95% Confidence Interval), 33.3% (15.6%-55.3%) and 18.2% (5.2%-40.3%) for the 30 mg, 40 mg and 50 mg arms (p-value = 0.56). Objective response was seen in 2 patients with NSCLC (treated at 30 and 50 mg respectively), one with BC (at 40 m g) and one with PC (at 50 mg) and lasted from 4 to 100 weeks, with maximum response duration achieved at 50 mg. Adverse events were mild and negligible and did not differ between the three arms. Blood levels of vinorelbine reached steady state from the second week of treatment and mean values for the 30, 40 and 50 mg were respectively 1.8 ng/ml (SD 1.10), 2.2 ng/ml (SD 1.87) and 2.6 ng/ml (SD 0.69). Low pre-treatment blood concentrations of FGF2 and IL8 predicted favorable response to therapy (p values 0.02 and 0.006, respectively), while high levels of TEK gene transcript predicted treatment resistance. Considering the antitumor activity and response duration, the negligible toxicity of the highest dose investigated and the lack of drug accumulation over time, we suggest that 50 mg given three times a week is the

  6. Failure of antimony trioxide to induce micronuclei or chromosomal aberrations in rat bone-marrow after sub-chronic oral dosing.

    Science.gov (United States)

    Kirkland, David; Whitwell, James; Deyo, James; Serex, Tessa

    2007-03-05

    Antimony trioxide (Sb2O3, CAS 1309-64-4) is widely used as a flame retardant synergist in a number of household products, as a fining agent in glass manufacture, and as a catalyst in the manufacture of various types of polyester plastics. It does not induce point mutations in bacteria or mammalian cells, but is able to induce chromosomal aberrations (CA) in cultured cells in vitro. Although no CA or micronuclei (MN) have been induced after acute oral dosing of mice, repeated oral dosing for 14 or 21 days resulted in increased CA in one report, but did not result in increased MN in another. In order to further investigate its in vivo genotoxicity, Sb2O3 was dosed orally to groups of rats for 21 days at 250, 500 and 1000 mg/kg day. There were no clinical signs of toxicity in the Sb2O3-exposed animals except for some reductions in body-weight gain in the top dose group. Toxicokinetic measurements in a separate study confirmed bone-marrow exposure, and at higher levels than would have been achieved by single oral dosing. Large numbers of cells were scored for CA (600 metaphases/sex group) and MN (12,000 PCE/sex group) but frequencies of CA or MN in Sb2O3-treated rats were very similar to controls, and not biologically or statistically different, at all doses. These results provide further indication that Sb2O3 is not genotoxic to the bone marrow of rodents after 21 days of oral administration at high doses close to the maximum tolerated dose.

  7. Assessment of driving capability through the use of clinical and psychomotor tests in relation to blood cannabinoids levels following oral administration of 20 mg dronabinol or of a cannabis decoction made with 20 or 60 mg Delta9-THC.

    Science.gov (United States)

    Ménétrey, Annick; Augsburger, Marc; Favrat, Bernard; Pin, Marie A; Rothuizen, Laura E; Appenzeller, Monique; Buclin, Thierry; Mangin, Patrice; Giroud, Christian

    2005-01-01

    Delta(9)-Tetrahydrocannabinol (THC) is frequently found in the blood of drivers suspected of driving under the influence of cannabis or involved in traffic crashes. The present study used a double-blind crossover design to compare the effects of medium (16.5 mg THC) and high doses (45.7 mg THC) of hemp milk decoctions or of a medium dose of dronabinol (20 mg synthetic THC, Marinol on several skills required for safe driving. Forensic interpretation of cannabinoids blood concentrations were attempted using the models proposed by Daldrup (cannabis influencing factor or CIF) and Huestis and coworkers. First, the time concentration-profiles of THC, 11-hydroxy-Delta(9)-tetrahydrocannabinol (11-OH-THC) (active metabolite of THC), and 11-nor-9-carboxy-Delta(9)-tetrahydrocannabinol (THCCOOH) in whole blood were determined by gas chromatography-mass spectrometry-negative ion chemical ionization. Compared to smoking studies, relatively low concentrations were measured in blood. The highest mean THC concentration (8.4 ng/mL) was achieved 1 h after ingestion of the strongest decoction. Mean maximum 11-OH-THC level (12.3 ng/mL) slightly exceeded that of THC. THCCOOH reached its highest mean concentration (66.2 ng/mL) 2.5-5.5 h after intake. Individual blood levels showed considerable intersubject variability. The willingness to drive was influenced by the importance of the requested task. Under significant cannabinoids influence, the participants refused to drive when they were asked whether they would agree to accomplish several unimportant tasks, (e.g., driving a friend to a party). Most of the participants reported a significant feeling of intoxication and did not appreciate the effects, notably those felt after drinking the strongest decoction. Road sign and tracking testing revealed obvious and statistically significant differences between placebo and treatments. A marked impairment was detected after ingestion of the strongest decoction. A CIF value, which relies on the

  8. [Directions for use of corticosteroids and calcineurin inhibitors against generalized myasthenia gravis: therapeutic strategies that can lead to early improvements and veer away from high-dose oral corticosteroids].

    Science.gov (United States)

    Utsugisawa, Kimiaki; Nagane, Yuriko; Suzuki, Shigeaki; Suzuki, Norihiro

    2012-01-01

    The advent of effective immune treatment has meant that myasthenia gravis (MG) is most often not lethal. However, many MG patients still find it difficult to maintain daily activities due to chronic residual fatigability and long-term side effects of medication, since full remission without immune treatment is not common. Our analysis demonstrated that disease severity, dose of oral corticosteroids, and depressive state are the major independent factors negatively associated with self-reported QOL (MG-QOL15-J score). It is noteworthy that oral corticosteroid, the first-line agent for MG, is negatively associated with patients' QOL. When the analysis took into account MGFA postintervention status and dose of oral prednisolne (PSL), the MG-QOL15-J score of MM status patients taking ≤ 5 mg PSL per day is identically low (i.e., just as good QOL) as that seen in CSR and is a target of treatment. In order to veer away from high-dose oral corticosteroids and to achieve early MM or better status with PSL ≤ 5 mg/day, we advocate the early aggressive treatment strategy that can achieve early improvement by performing an aggressive therapy using combined treatment with plasmapheresis and high-dose intravenous methylprednisolone and then maintain an improved clinical status using low-dose oral corticosteroids and calcineurin inhibitors (cyclosporine microemulsion and tacrolimus). The early stages of MG are susceptible to treatment with calcineurin inhibitors. When using cyclosporine microemulsion for MG, blood concentrations 2 h after administration (C2) correlate with clinical improvement and immediately before administration (C0) with side effects (increased serum creatinine and/or hypertension). Monitoring of C2 and C0 levels is useful to estimate efficacy and safety of the drug.

  9. Measurements of low photon doses using LiF:Mg,Cu,P and CaF{sub 2}:Cu dosimeters

    Energy Technology Data Exchange (ETDEWEB)

    Prokert, K [Dresden Univ. of Technology (Germany). Inst. of Radiation Protection Physics; Mann, G [Dresden Univ. of Technology (Germany). Inst. of Radiation Protection Physics

    1997-03-01

    The new thermoluminophors LiF:Mg, Cu, P and CaF{sub 2}:Cu in form of pellets exhibit a significantly higher TL-response than the well-known dosimeters of the types TLD-100 (LiF:Mg, Ti), TLD-400 (CaF{sub 2}:Mn), TLD-900 (CaSO{sub 4}:Dy), etc. Furthermore, the thermoluminophor LiF:Mg, Cu, P shows besides its high sensitivity a good tissue equivalence and therefore, only a small variation of the dose response with the photon energy. The lower limits of detection of these new materials are about 5 {mu}Gy and 0.2 {mu}Gy resp. Therefore, short term measurements of absorbed dose can be realised in radiation fields at very low dose rates (environmental radiation, scattering radiation at medical equipment`s etc.) with an accuracy of {+-}10%. In the field of environmental monitoring the period of exposure can be limited to about 10 days. Using CaF{sub 2}:Cu detectors an exposure of 24 hours is sufficient for dose measurements with lower accuracy. The reusability of CaF{sub 2}:Cu pellets is guaranteed without loss of sensitivity independently of the application of different reading and annealing procedures. In the case of LiF:Mg, Cu, P detectors special procedures are needed in order to keep constant TL-properties. The results of dose measurements at low dose levels in different radiation fields demonstrate the advantages of these detector types. (orig.)

  10. Single oral dose toxicity test of polycalcium, a mixed composition of polycan and calcium lactate-gluconate 1:9 (G/G) in SD rat.

    Science.gov (United States)

    Kim, Joo-Wan; Choi, Jae-Suk; Ha, Yu-Mi; Choi, In Soon; Kim, Ki-Young; Cho, Hyung-rae; Rha, Chae-hun; Ku, Sae-Kwang

    2013-11-01

    The object of this study was to obtain acute oral toxicity information of Polycalcium, a mixed composition of Polycan and Calcium lactate-gluconate 1:9 (g/g), in Sprague-Dawely (SD) rats. In order to investigate the toxicity and identify target organs, Polycalcium were once orally administered to female and male SD rats at dose levels of 2000, 1000, 500 and 0 (control) mg/kg body weights. The mortality, changes on body weight and clinical signs were monitored during 14 days after treatment with gross observation, changes on the organ weights and histopathology of principle organs and treatment sites based on the recommendation of KFDA Guidelines [2009-116, 2009]. As the results of single oral treatment of Polycalcium, no treatment related mortalities were observed within 14 days after end of treatment up to 2000 mg/kg, the limited dosage of rodents in the both genders. In addition, no Polycalcium treatment related changes on the body and organ weights, clinical signs, necropsy and histopathological findings were detected. The results obtained in this study suggest that the Polycalcium is non-toxic in rats. The LD50 and approximate LD in rats after single oral dose of Polycalcium were considered over 2000 mg/kg in both female and male, respectively.

  11. Perturbation of cobalt 60 radiation doses by metal objects implanted during oral and maxillofacial surgery

    International Nuclear Information System (INIS)

    Tatcher, M.; Kuten, A.; Helman, J.; Laufer, D.

    1984-01-01

    The influence on cobalt 60 dose distributions of typical metal parts used in oral and maxillofacial surgery was studied. Relative doses were determined by exposing x-ray films in a polystyrene phantom set-up containing samples of vitallium, titanium, and stainless steel. Optical densities were converted to doses with the aid of sensitometric curves. The results show that for normal incidence there is a 25% to 40% increase in dose at the entrance side of the metal and a 20% to 25% decrease in dose at the exit side. The enhancement effect falls off rapidly and becomes negligible at about 1 mm from the interface. The reduction effect decreases more gradually and is still evident at distances of a few centimeters. These dose perturbations should be taken into account in the planning of radiation therapy for patients in whom metal objects have been implanted

  12. Comparing the Efficacy of Low Dose and Conventional Dose of Oral Isotretinoin in Treatment of Moderate and Severe Acne Vulgaris.

    Science.gov (United States)

    Faghihi, Gita; Mokhtari, Fatemeh; Fard, Nasrin Motamedi; Motamedi, Narges; Hosseini, Sayed Mohsen

    2017-01-01

    This study was conducted to compare the effect of low-dose isotretinoin with its conventional dose in patients with moderate and severe acne. This was a clinical trial conducted on 60 male and female patients with moderate and severe acne vulgaris. The patients were divided into two treatment groups: 0.5 mg/kg/day isotretinoin capsule and low-dose isotretinoin capsule (0.25 mg/kg/day). Patients in both groups received 6-month treatment. At the end of the 6 th month and 12 th month (6 months after the end of the treatment), they were examined again, and their improvement was determined and compared. The average severity of acne in the two treatment groups did not differ significantly within any of the study periods. The most common side effects were nose dryness in the low-dose group (17%) and hair thinning and loss in the conventional-dose group (33.2%), although all the patients had dry lips. According to the same severity of the acne in two groups in different study periods, as well as fewer side effects and more patients' satisfaction, the low-dose isotretinoin can be considered in the treatment of acne.

  13. Simulated rat intestinal fluid improves oral exposure prediction for poorly soluble compounds over a wide dose range

    Directory of Open Access Journals (Sweden)

    Joerg Berghausen

    2016-03-01

    Full Text Available Solubility can be the absorption limiting factor for drug candidates and is therefore a very important input parameter for oral exposure prediction of compounds with limited solubility. Biorelevant media of the fasted and fed state have been published for humans, as well as for dogs in the fasted state. In a drug discovery environment, rodents are the most common animal model to assess the oral exposure of drug candidates. In this study a rat simulated intestinal fluid (rSIF is proposed as a more physiologically relevant media to describe drug solubility in rats. Equilibrium solubility in this medium was tested as input parameter for physiologically-based pharmacokinetics (PBPK simulations of oral pharmacokinetics in the rat. Simulations were compared to those obtained using other solubility values as input parameters, like buffer at pH 6.8, human simulated intestinal fluid and a comprehensive dissolution assay based on rSIF. Our study on nine different compounds demonstrates that the incorporation of rSIF equilibrium solubility values into PBPK models of oral drug exposure can significantly improve the reliability of simulations in rats for doses up to 300 mg/kg compared to other media. The comprehensive dissolution assay may help to improve further simulation outcome, but the greater experimental effort as compared to equilibrium solubility may limit its use in a drug discovery environment. Overall, PBPK simulations based on solubility in the proposed rSIF medium can improve prioritizing compounds in drug discovery as well as planning dose escalation studies, e.g. during toxicological investigations.

  14. Placental transfer and pharmacokinetics of a single oral dose of [14C] p-nitrophenol in rats

    International Nuclear Information System (INIS)

    Abu-Qare, A.W.; Brownie, C.F.; Abou-Donia, M.B.

    2000-01-01

    The pharmacokinetics and placental transfer of a single oral dose of 100 mg/kg (10 μCi/kg, 16% of acute oral LD 50 ) of uniformly phenyl-labeled [ 14 C]p-nitrophenol were investigated in pregnant Sprague-Dawley rats at 14-18 days of gestation. Three animals were killed on gestation day 18, at 0.5, 1, 2, 4, 12, 24, and 48 h after dosing. Radioactivity was rapidly absorbed and distributed throughout the maternal and fetal tissues. The gastrointestinal tract contents retained 20% and 2% of the dose at 0.5 h and 4 h after dosing. The peak maternal plasma concentration of radioactivity (μg p-nitrophenol equivalent/ml) was 7.17 compared with 0.37 for fetal plasma at 0.5 h. Maximum concentration of radioactivity (μg p-nitrophenol equivalent/g fresh tissue) was detected in most tissues 0.5 h after dosing and was in descending order: kidney 23.27, liver 12.37, placenta 3.56, fetus 2.17, and brain 1.99. Radioactivity was eliminated from plasma and all tissues beiexponentially. The half-lives of elimination of 14 C were 34.65 h and 69.30 h for maternal and fetal plasma, respectively. p-Nitrophenol, detected by HPLC, was the major compound identified in plasma and tissues. While p-nitrophenol disappeared biphasically from maternal plasma and kidney, it was eliminated monophasically from brain, placenta, and liver. p-Nitrocatechol and p-aminophenol were detected in the liver with peak concentrations at 0.5 h of 1.13 and 1.00 μg/g fresh tissue, respectively. While the change in the concentration of p-nitrocatechol with time was monophasic, that of p-aminophenol showed a biphasic pattern with elimination half-lives of 1.93 h and 4.95 h, respectively. Radioactivity was rapidly excreted in the urine mostly as polar metabolites, while only 3% of the dose was recovered in the feces. Radioactive materials excreted in the urine comprised: glucuronides 4%, sulfates 8%, hot-acid hydrolysates 11%, nonconjugated compounds 16%, and water-soluble metabolites 61%. This study demonstrated

  15. Serum toxicokinetics after intravenous and oral dosing of larkspur toxins in goats

    Science.gov (United States)

    Poisoning of cattle by larkspur plants (Delphinium spp.) is a concern for cattle ranchers in western North America. Previous research studies have evaluated the toxicokinetic profile of multiple larkspur toxins in several livestock species. However, those studies were all performed by orally dosing ...

  16. Proposed Oral Reference Dose (RfD) for Barium and Compounds (Final Report, 2004)

    Science.gov (United States)

    This document is the final report from the 2004 external peer review of the Proposed Oral Reference Dose (RfD) for Barium and Compounds, prepared by the U.S. Environmental Protection Agency (EPA), National Center for Environmental Assessment (NCEA), for the Integrated Risk...

  17. Successful Treatment of Dry Mouth and Dry Eye Symptoms in Sjögren's Syndrome Patients With Oral Pilocarpine: A Randomized, Placebo-Controlled, Dose-Adjustment Study.

    Science.gov (United States)

    Papas, Athena S; Sherrer, Yvonne S; Charney, Michael; Golden, Harvey E; Medsger, Thomas A; Walsh, Bridget T; Trivedi, Madhu; Goldlust, Barry; Gallagher, Susan C

    2004-08-01

    : Sjögren's syndrome is characterized by the presence of xerostomia and/or xerophthalmia. Pilocarpine, a muscarinic cholinergic agonist, has been proven to be efficacious in treating radiation-induced xerostomia (up to 30 mg/day) and symptoms of dry mouth in Sjögren's patients (up to 20 mg/day). : To compare the safety and efficacy of oral pilocarpine (dose-adjusted) versus placebo in the treatment of dry eye and dry mouth symptoms in Sjögren's syndrome at 6 and 12 weeks. : In this 11-center, 256-patient placebo-controlled study, the safety and efficacy of oral pilocarpine (20 mg to 30 mg daily) for relief of Sjögren's-related dry mouth and dry eye symptoms was assessed. Changes in symptoms and salivary flow were measured over 12 weeks. : Compared with placebo, salivary flow was significantly increased in the pilocarpine group (Pdry mouth (Poral symptoms (Pdry eyes (Pdry mouth symptoms was noted at 20 mg/day, and significant relief in ocular symptoms, including lower artificial tear requirement, was noted after the dose was increased to 30 mg/day.

  18. [LIRAGUTIDE AT A DOSE OF 3.0 MG (SAXENDA): NEW INDICATION FOR THE TREATMENT OF OBESITY].

    Science.gov (United States)

    Scheen, A J

    2016-05-01

    Liraglutide is an analogue of Glucagon-Like Peptide-1 (GLP-1) already indicated under the trade name of Victoza for the treatment of type 2 diabetes, at usual doses of 1.2 or 1.8 mg as once daily subcutaneous injection. It is henceforth indicated at a dose of 3.0 mg, also as once daily subcutaneous injection, for the treatment of obesity or overweight with comorbidities under the trade name of Saxenda, in combination with diet and exercise. Besides a specific action on the endocrine pancreas, mainly responsible for the antihyperglycaemic effect, liraglutide helps controlling appetite at the hypothamalic level. A specific programme of controlled trials (especially SCALE studies) demonstrated both efficacy and safety of the 3.0 mg dose of liraglutide in obese or overweight patients with various comorbidities.

  19. A multiple-dose, double-blind comparison of intramuscularly and orally administered ketorolac tromethamine and Ketogan in patients with pain following orthopaedic surgery

    DEFF Research Database (Denmark)

    Gebuhr, Peter Henrik; Soelberg, M; Strauss, W

    1994-01-01

    In this multiple-dose, double-blind study 100 patients with moderate, severe or very severe pain following orthopaedic surgery were randomly assigned to receive ketorolac, a non-steroidal anti-inflammatory drug with potent analgesic properties (10 mg), or the standard regimen of Ketogan (a combin......-mg doses of oral ketorolac are as effective as Ketogan for the treatment of pain following orthopaedic surgery. Ketorolac appears to be better tolerated than Ketogan since significantly fewer patients reported adverse events (P = 0.004) when taking ketorolac.......In this multiple-dose, double-blind study 100 patients with moderate, severe or very severe pain following orthopaedic surgery were randomly assigned to receive ketorolac, a non-steroidal anti-inflammatory drug with potent analgesic properties (10 mg), or the standard regimen of Ketogan (a...... combination product containing the narcotic analgesic, ketobemidone, plus a spasmolytic agent) by intramuscular injection every 1-6 h as needed for pain. When patients were able to tolerate an oral diet and were expected to respond to oral analgesic medication, based on overall pain sensitivity, they were...

  20. Safety and efficacy of fixed-dose 10 mg daily isotretinoin treatment for acne vulgaris in Malaysia.

    Science.gov (United States)

    Yap, Felix Boon-Bin

    2017-09-01

    Low-dose isotretinoin is used to reduce side effects albeit higher relapse. This study aimed to determine the efficacy and safety of fixed-dose 10 mg daily isotretinoin for the treatment of acne. This prospective study was performed between 2011 and 2015. All 150 patients were given 10 mg daily isotretinoin until a cumulative dose of 90-110 mg/kg. The mean age was 26.6 years with 64.7% moderate acne, 29.3% severe, and 6% very severe. The mean cumulative dose was 98.8 ± 6.05 mg/kg. All 150 patients had total clearance with a mean time to clearance of 24.0 weeks. Patients with severe/very severe acne had higher cumulative dosage (102.1 vs. 97.0, P < 0.001) and longer duration to clearance (32.9 weeks vs. 19.1 weeks, P < 0.001). Mild relapse was seen in 4%. The mean time to relapse was 32.3 weeks. Lip dryness was the commonest side effects (100%). Mild transient elevation of liver enzymes was detected in 3.3% and a slight increase of serum lipid in 2.7% with no treatment discontinuation. Fixed-dose 10 mg daily treatment with isotretinoin until a cumulative dose of 90-110 mg/kg is safe with low relapse rate. © 2016 Wiley Periodicals, Inc.

  1. Thermoluminescent characteristics of LiF:Mg, Cu, P and CaSO_4:Dy for low dose measurement

    International Nuclear Information System (INIS)

    Del Sol Fernández, S.; García-Salcedo, R.; Mendoza, J. Guzmán; Sánchez-Guzmán, D.; Rodríguez, G. Ramírez; Gaona, E.; Montalvo, T. Rivera

    2016-01-01

    Thermoluminescence (TL) characteristics for LiF:Mg, Cu, P, and CaSO_4:Dy under the homogeneous field of X-ray beams of diagnostic irradiation and its verification using thermoluminescence dosimetry are presented. The irradiation were performed utilizing a conventional X-ray equipment installed at the Hospital Juárez Norte of México. Different thermoluminescence characteristics of two material were studied, such as batch homogeneity, glow curve, linearity, detection threshold, reproducibility, relative sensitivity and fading. Materials were calibrated in terms of absorbed dose to the standard calibration distance and they were positioned in a generic phantom. The dose analysis, verification and comparison with the measurements obtained by the TLD-100 were performed. Results indicate that the dosimetric peak appears at 202 °C and 277.5 °C for LiF:Mg, Cu, P and CaSO_4:Dy, respectively. TL response as a function of X-ray dose showed a linearity behavior in the very low dose range for all materials. However, the TLD-100 is not accurate for measurements below 4 mGy. CaSO_4:Dy is 80% more sensitive than TLD-100 and it show the lowest detection threshold, whereas LiF:Mg, Cu, P is 60% more sensitive than TLD-100. All materials showed very good repeatability. Fading for a period of one month at room temperature showed low fading LiF:Mg, Cu, P, medium and high for TLD-100 and CaSO_4:Dy. The results suggest that CaSO_4:Dy and LiF:Mg, Cu, P are suitable for measurements at low doses used in radiodiagnostic. - Highlights: • Several dosimetric characteristics were evaluated. • TL dose response to very low dose X-rays was studied. • The applications proposed for each material may be useful for diagnostic radiology dosimetry.

  2. Multiple-dose pharmacokinetic study of proguanil and cycloguanil following 12-hourly administration of 100 mg proguanil hydrochloride.

    Science.gov (United States)

    Jamaludin, A; Mohamad, M; Navaratnam, V; Yeoh, P Y; Wernsdorfer, W H

    1990-09-01

    A pharmacokinetic study with 12-hourly doses of 100 mg proguanil hydrochloride over 15 days has been conducted in six adult male Malaysian volunteers. Steady state for proguanil was established after the fourth dose on Day 2, for the active metabolite cycloguanil as from Day 3 inclusive. The steady state mean peak concentration of proguanil was 1201.6 +/- 132.4 nmol/l, the mean trough concentration 650.0 +/- 58.1 nmol/l. The corresponding values for cycloguanil were 317.0 +/- 44.4 nmol/l (mean peak) and 230.8 +/- 35.1 nmol/l (mean trough). The profiles and peak/trough ratios of proguanil and cycloguanil with 12-hourly dosing offer better prospects for protection against malaria than those obtained with 24-hourly doses of 200 mg proguanil hydrochloride, the current routine in malaria chemoprophylaxis.

  3. Effect of combined oral doses of Δ(9)-tetrahydrocannabinol (THC) and cannabidiolic acid (CBDA) on acute and anticipatory nausea in rat models.

    Science.gov (United States)

    Rock, Erin M; Connolly, Cassidy; Limebeer, Cheryl L; Parker, Linda A

    2016-09-01

    The purpose of this study was to evaluate the potential of oral combined cannabis constituents to reduce nausea. The objective of this study was to determine the effect of combining subthreshold oral doses of Δ(9)-tetrahydrocannabinol (THC) and cannabidiolic acid (CBDA) on acute and anticipatory nausea in rat models of conditioned gaping. The potential of intragastric (i.g.) administration of THC, CBDA, or combined doses, to interfere with acute nausea-induced conditioned gaping (acute nausea) or the expression of contextually elicited conditioned gaping (anticipatory nausea), was evaluated. For acute nausea, i.g. administration of subthreshold doses of THC (0.5 and 1 mg/kg) or CBDA (0.5 and 1 μg/kg) significantly suppressed acute nausea-induced gaping, whereas higher individual doses of both THC and CBDA were maximally effective. Combined i.g. administration of higher doses of THC and CBDA (2.5 mg/kg THC-2.5 μg/kg CBDA; 10 mg/kg THC-10 μg/kg CBDA; 20 mg/kg THC-20 μg/kg CBDA) also enhanced positive hedonic reactions elicited by saccharin solution during conditioning. For anticipatory nausea, combined subthreshold i.g. doses of THC (0.1 mg/kg) and CBDA (0.1 μg/kg) suppressed contextually elicited conditioned gaping. When administered i.g., THC was effective on its own at doses ranging from 1 to 10 mg/kg, but CBDA was only effective at 10 μg/kg. THC alone was equally effective by intraperitoneal (i.p.) and i.g. administration, whereas CBDA alone was more effective by i.p. administration (Rock et al. in Psychopharmacol (Berl) 232:4445-4454, 2015) than by i.g. administration. Oral administration of subthreshold doses of THC and CBDA may be an effective new treatment for acute nausea and anticipatory nausea and appetite enhancement in chemotherapy patients.

  4. Results in patients treated with high-dose-rate interstitial brachytherapy for oral tongue cancer

    International Nuclear Information System (INIS)

    Yamamoto, Michinori; Shirane, Makoto; Ueda, Tsutomu; Miyahara, Nobuyuki

    2006-01-01

    Eight patients were treated with high-dose-rate interstitial brachytherapy for oral tongue cancer between September 2000 and August 2004. The patient distribution was 1 T1, 5 T2, 1 T3, and 1 T4a. Patients received 50-60 Gy in 10 fractions over seven days with high-dose-rate brachytherapy. Six of the eight patients were treated with a combination of external beam radiotherapy (20-30 Gy) and interstitial brachytherapy. The two-year primary local control rate was 83% for initial case. High-dose-rate brachytherapy was performed safely even for an aged person, and was a useful treatment modality for oral tongue cancer. (author)

  5. Implementation research: reactive mass vaccination with single-dose oral cholera vaccine, Zambia.

    Science.gov (United States)

    Poncin, Marc; Zulu, Gideon; Voute, Caroline; Ferreras, Eva; Muleya, Clara Mbwili; Malama, Kennedy; Pezzoli, Lorenzo; Mufunda, Jacob; Robert, Hugues; Uzzeni, Florent; Luquero, Francisco J; Chizema, Elizabeth; Ciglenecki, Iza

    2018-02-01

    To describe the implementation and feasibility of an innovative mass vaccination strategy - based on single-dose oral cholera vaccine - to curb a cholera epidemic in a large urban setting. In April 2016, in the early stages of a cholera outbreak in Lusaka, Zambia, the health ministry collaborated with Médecins Sans Frontières and the World Health Organization in organizing a mass vaccination campaign, based on single-dose oral cholera vaccine. Over a period of 17 days, partners mobilized 1700 health ministry staff and community volunteers for community sensitization, social mobilization and vaccination activities in 10 townships. On each day, doses of vaccine were delivered to vaccination sites and administrative coverage was estimated. Overall, vaccination teams administered 424 100 doses of vaccine to an estimated target population of 578 043, resulting in an estimated administrative coverage of 73.4%. After the campaign, few cholera cases were reported and there was no evidence of the disease spreading within the vaccinated areas. The total cost of the campaign - 2.31 United States dollars (US$) per dose - included the relatively low cost of local delivery - US$ 0.41 per dose. We found that an early and large-scale targeted reactive campaign using a single-dose oral vaccine, organized in response to a cholera epidemic within a large city, to be feasible and appeared effective. While cholera vaccines remain in short supply, the maximization of the number of vaccines in response to a cholera epidemic, by the use of just one dose per member of an at-risk community, should be considered.

  6. An outpatient regimen of combined oral mifepristone 400 mg and misoprostol 400 microg for first-trimester legal medical abortion

    DEFF Research Database (Denmark)

    Ravn, Pernille; Rasmussen, Ase; Knudsen, Ulla Breth

    2005-01-01

    AIM: To evaluate the success rate of medical abortion using an outpatient regimen of oral mifepristone 400 mg and oral misoprostol 400 microg for legal abortion in women abortion was defined as an endometrial thickness ... the procedure over a 3-year period and 606 (92%) experienced successful medical abortion. The remaining 8% had vacuum aspiration performed mainly due to uterine retention (70%). Other reasons were vaginal bleeding (25%), vomiting (2%), or pelvic infection (4%). Most women reported no days with severe pain (67......%), 0--1 days with moderate pain (82%), and 0--1 days with light pain (62%). In terms of gastrointestinal side effects, 68% reported nausea, 33% vomiting, and 27% diarrhea. Most women (90%) felt that the information given at the hospital prior to the abortion was sufficient, 74% would prefer medical...

  7. Evaluation of fleroxacin (RO 23-6240) as single-oral-dose therapy of culture-proven chancroid in Nairobi, Kenya.

    Science.gov (United States)

    MacDonald, K S; Cameron, D W; D'Costa, L; Ndinya-Achola, J O; Plummer, F A; Ronald, A R

    1989-01-01

    Chancroid is gaining importance as a sexually transmitted disease because of its association with transmission of human immunodeficiency virus type 1 (HIV-1). Effective, simply administered therapy for chancroid is necessary. Fleroxacin is effective against Haemophilus ducreyi in vitro. We performed an initial randomized clinical trial to assess the efficacy of fleroxacin for treatment of chancroid in Nairobi, Kenya. Fifty-three men with culture-positive chancroid were randomly assigned to receive either 200 mg (group 1) or 400 mg (group 2) of fleroxacin as a single oral dose. Groups 1 and 2 were similar with regard to severity of disease, bubo formation, and HIV-1 status. A satisfactory clinical response to therapy was noted in 23 of 26 patients (88%) in group 1 and 18 of 23 patients (78%) in group 2. Bacteriological failure occurred in 1 of 26 evaluable patients (4%) in group 1 and 4 of 23 evaluable patients (17%) in group 2. Two of 37 HIV-1-seronegative men (5%) and 3 of 11 HIV-1-infected men (27%) were bacteriological failures. Fleroxacin, 200 or 400 mg as a single oral dose, is efficacious therapy for microbiologically proven chancroid in patients who do not have concurrent HIV-1 infection. Among HIV-1-infected men, a single dose of 200 or 400 mg of fleroxacin is inadequate therapy for chancroid. PMID:2502065

  8. Usefulness of low dose oral contrast media in 18F-FDG PET/CT

    International Nuclear Information System (INIS)

    An, Young Sil; Yoon, Joon Kee; Hong, Seon Pyo; Joh, Chul Woo; Yoon, Seok Nam

    2006-01-01

    The standard protocol using large volume of oral contrast media may cause gastrointestinal discomfort and contrast-related artifacts in PET/CT. The aim of this study was to evaluate the usefulness of low dose oral contrast in 18 F-FDG PET/CT. We retrospectively reviewed the whole-body PET/CT images in a total of 435 patients. About 200 ml of oral contrast agent (barium sulfate) was administered immediately before injection of 18 F-FDG. The FDG uptake of intestines was analyzed by visual and semi-quantitative method on transaxial, coronal and saggital planes. Seventy (16%, 113 sites) of 435 images showed high FDG uptake (peak SUV > 4); 50 (74%, 84 sites) with diffuse and 20 (26%, 29 sites) with focal uptake. The most commonly delivered site of oral contrast media was small bowel (n = 27, 39%). On PET/CT images, FDG uptake coexisted with oral contrast media in 26 patients (54%, 38 sites) with diffuse pattern and 9 (45%, 9 sites) with focal pattern, and by sites, those were 38 (45%) and 9 (31%), respectively. In small bowel regions, the proportion of coexistence reached as high as 61% (29/47 sites). A visual analysis of available non-attenuation corrected PET images of 27 matched regions revealed no contrast-related artifact. We concluded that the application of low dose contrast media could be helpful in the evaluation of abdominal uptake in the FDG PET/CT image

  9. Usefulness of low dose oral contrast media in FDG PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    An, Y. S.; Yun, J. G.; Lee, M. H.; Cho, C. W.; Yun, S. N [Ajou University Medical Center, Suwon (Korea, Republic of)

    2004-07-01

    Oral contrast media might help in interpreting PET/CT images, allowing better discrimination between physiologic and pathologic abdominal uptake. The aim of this study was to evaluate the usefulness of low dose oral contrast on FDG PET/CT. A total of 435 cancer patients received 200mL of oral Barium with water(200mL) immediately before FDG injection. PET images were reconstructed using attenuation correction and iterative reconstruction. The FDG uptake in gastrointestinal(GI) tract were analyzed by visual and semiquantitative method in transaxial, coronal and sagittal planes. Seventy patients(16%, 113 sites) of 435 images showed high FDG uptake(pSUV>4.0) : 50(74%, 84 sites) with diffuse uptake and 20(26%, 29sites) with focal uptake. The most common distribution site of oral contrast media was small bowel (n=27, 39%) and others were small bowel with transverse colon(n=6, 8%), small bowel with ascending and sigmoid colon(n=6, 8%) and etc. In PET/CT images, FDG uptake coexisted with oral contrast was showed in 26 patients(54%) with diffuse pattern and 9(45%) with focal pattern, and by sites, those were 38(45%) and 9(31%), respectively. In small bowel regions, the most common distribution site, the proportion of coexistence reached as high as 61% (29 in the total 47 sites). Application of low dose contrast agent can be helpful in the evaluation of intestinal uptake in FDG PET/CT image.

  10. Usefulness of low dose oral contrast media in FDG PET/CT

    International Nuclear Information System (INIS)

    An, Y. S.; Yun, J. G.; Lee, M. H.; Cho, C. W.; Yun, S. N

    2004-01-01

    Oral contrast media might help in interpreting PET/CT images, allowing better discrimination between physiologic and pathologic abdominal uptake. The aim of this study was to evaluate the usefulness of low dose oral contrast on FDG PET/CT. A total of 435 cancer patients received 200mL of oral Barium with water(200mL) immediately before FDG injection. PET images were reconstructed using attenuation correction and iterative reconstruction. The FDG uptake in gastrointestinal(GI) tract were analyzed by visual and semiquantitative method in transaxial, coronal and sagittal planes. Seventy patients(16%, 113 sites) of 435 images showed high FDG uptake(pSUV>4.0) : 50(74%, 84 sites) with diffuse uptake and 20(26%, 29sites) with focal uptake. The most common distribution site of oral contrast media was small bowel (n=27, 39%) and others were small bowel with transverse colon(n=6, 8%), small bowel with ascending and sigmoid colon(n=6, 8%) and etc. In PET/CT images, FDG uptake coexisted with oral contrast was showed in 26 patients(54%) with diffuse pattern and 9(45%) with focal pattern, and by sites, those were 38(45%) and 9(31%), respectively. In small bowel regions, the most common distribution site, the proportion of coexistence reached as high as 61% (29 in the total 47 sites). Application of low dose contrast agent can be helpful in the evaluation of intestinal uptake in FDG PET/CT image

  11. The effect of single oral doses of duloxetine, reboxetine, and midodrine on the urethral pressure in healthy female subjects, using urethral pressure reflectometry

    DEFF Research Database (Denmark)

    Klarskov, Niels; Cerneus, Dirk; Sawyer, William

    2018-01-01

    AIMS: To evaluate the effect on urethral pressure of reference drugs known to reduce stress urinary incontinence symptoms by different effect size and mechanisms of action on urethral musculature under four test conditions in healthy female subjects using urethral pressure reflectometry. METHODS......: Healthy females aged 18-55 years were recruited by advertising for this phase 1, single site, placebo-controlled, randomized, four-period, crossover study. The interventions were single oral doses of 10 mg Midodrine, 80 mg Duloxetine, 12 mg Reboxetine, and placebo. The endpoints were the opening urethral...... pressure measured in each period at four time points (predose and 2, 5.5, and 9 h after dosing). RESULTS: Twenty-nine females were enrolled; 25 randomized and 24 completed the study. The opening urethral pressure was higher in all measurements with filled bladder compared with empty bladder, and during...

  12. High-dose-rate brachytherapy using molds for oral cavity cancer. The technique and its limitations

    International Nuclear Information System (INIS)

    Nishimura, Yasumasa; Yokoe, Yoshihiko; Nagata, Yasushi; Okajima, Kaoru; Nishida, Mitsuo; Hiraoka, Masahiro

    1998-01-01

    With the availability of a high-dose-rate (HDR) remote afterloading device, a Phase I/II protocol was initiated at our institution to assess the toxicity and efficacy of HDR intracavitary brachytherapy, using molds, in the treatment of squamous cell carcinomas of the oral cavity. Eight patients with squamous cell carcinoma of the oral cavity were treated by the technique. The primary sites of the tumors were the buccal mucosa, oral floor, and gingiva. Two of the buccal mucosal cancers were located in the retromolar trigon. For each patient, a customized mold was fabricated, in which two to four afterloading catheters were placed for an 192 Ir HDR source. Four to seven fractions of 3-4 Gy, 5 mm below the mold surface, were given following external radiation therapy of 40-60 Gy/ 2 Gy. The total dose of HDR brachytherapy ranged from 16 to 28Gy. Although a good initial complete response rate of 7/8 (88%) was achieved, there was local recurrence in four of these seven patients. Both of the retromolar trigon tumors showed marginal recurrence. No serious (e.g., ulcer or bone exposure) late radiation damage has been observed thus far in the follow up period of 15-57 months. High-dose-rate brachytherapy using the mold technique seems a safe and useful method for selected early and superficial oral cavity cancer. However, it is not indicated for thick tumors and/or tumors located in the retromolar trigon. (author)

  13. Stability in the rumen and effect on plasma status of single oral doses of vitamin D and vitamin E in high-yielding dairy cows

    DEFF Research Database (Denmark)

    Hymøller, Lone; Jensen, Søren Krogh

    2010-01-01

    The ruminal fate of the fat-soluble vitamins D and E was studied in dairy cows. Ten to 15 kg of ruminal contents was taken from each cow through a ruminal fistula. A sample was taken out (0-h sample) and the rest of the contents were mixed with 4,360 mg of all-rac-α-tocopheryl acetate (vitamin E;...... a single dose of α-tocopheryl acetate led to the conclusion that oral single dose therapy with all-rac-α-tocopheryl acetate is of limited physiological value....

  14. The applicability of the PTTL dose re-analysis method to the Harshaw LiF:Mg,Cu,P material

    International Nuclear Information System (INIS)

    Moscovitch, M.; Benevides, L.; Romanyukha, A.; Hull, F.; Duffy, M.; Voss, S.; Velbeck, K. J.; Nita, I.; Rotunda, J. E.

    2011-01-01

    The photo-transferred thermoluminescence (PTTL) technique is applied to the Harshaw LiF:Mg,Cu,P material. It is demonstrated that using 254-nm UV light, dose levels as low as 0.2 mGy can be re-estimated. The PTTL efficiency was found to be ∼6 % in the dose range of 0.2 mGy -1 Gy, and it appears to be dose-independent. This implies that a simple calibration factor could be applied to the PTTL data for the re-estimation of dose levels. It was demonstrated that with a proper choice of the TL readout parameters, and the UV-light irradiation conditions, dose levels that are relevant to personal or environmental dosimetry can be re-estimated. (authors)

  15. Errors detected in pediatric oral liquid medication doses prepared in an automated workflow management system.

    Science.gov (United States)

    Bledsoe, Sarah; Van Buskirk, Alex; Falconer, R James; Hollon, Andrew; Hoebing, Wendy; Jokic, Sladan

    2018-02-01

    The effectiveness of barcode-assisted medication preparation (BCMP) technology on detecting oral liquid dose preparation errors. From June 1, 2013, through May 31, 2014, a total of 178,344 oral doses were processed at Children's Mercy, a 301-bed pediatric hospital, through an automated workflow management system. Doses containing errors detected by the system's barcode scanning system or classified as rejected by the pharmacist were further reviewed. Errors intercepted by the barcode-scanning system were classified as (1) expired product, (2) incorrect drug, (3) incorrect concentration, and (4) technological error. Pharmacist-rejected doses were categorized into 6 categories based on the root cause of the preparation error: (1) expired product, (2) incorrect concentration, (3) incorrect drug, (4) incorrect volume, (5) preparation error, and (6) other. Of the 178,344 doses examined, 3,812 (2.1%) errors were detected by either the barcode-assisted scanning system (1.8%, n = 3,291) or a pharmacist (0.3%, n = 521). The 3,291 errors prevented by the barcode-assisted system were classified most commonly as technological error and incorrect drug, followed by incorrect concentration and expired product. Errors detected by pharmacists were also analyzed. These 521 errors were most often classified as incorrect volume, preparation error, expired product, other, incorrect drug, and incorrect concentration. BCMP technology detected errors in 1.8% of pediatric oral liquid medication doses prepared in an automated workflow management system, with errors being most commonly attributed to technological problems or incorrect drugs. Pharmacists rejected an additional 0.3% of studied doses. Copyright © 2018 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

  16. Single oral dose pharmacokinetics of decursin and decursinol angelate in healthy adult men and women.

    Directory of Open Access Journals (Sweden)

    Jinhui Zhang

    Full Text Available The ethanol extract of Angelica gigas Nakai (AGN root has promising anti-cancer and other bioactivities in rodent models. It is currently believed that the pyranocoumarin isomers decursin (D and decursinol angelate (DA contribute to these activities. We and others have documented that D and DA were rapidly converted to decursinol (DOH in rodents. However, our in vitro metabolism studies suggested that D and DA might be metabolized differently in humans. To test this hypothesis and address a key question for human translatability of animal model studies of D and DA or AGN extract, we conducted a single oral dose human pharmacokinetic study of D and DA delivered through an AGN-based dietary supplement Cogni.Q (purchased from Quality of Life Labs, Purchase, NY in twenty healthy subjects, i.e., 10 men and 10 women, each consuming 119 mg D and 77 mg DA from 4 vegicaps. Analyses of plasma samples using UHPLC-MS/MS showed mean time to peak concentration (Tmax of 2.1, 2.4 and 3.3 h and mean peak concentration (Cmax of 5.3, 48.1 and 2,480 nmol/L for D, DA and DOH, respectively. The terminal elimination half-life (t1/2 for D and DA was similar (17.4 and 19.3 h and each was much longer than that of DOH (7.4 h. The mean area under the curve (AUC0-48h for D, DA and DOH was estimated as 37, 335 and 27,579 h∙nmol/L, respectively. Gender-wise, men absorbed the parent compounds faster and took shorter time to reach DOH peak concentration. The human data supported an extensive conversion of D and DA to DOH, even though they metabolized DA slightly slower than rodents. Therefore, the data generated in rodent models concerning anti-cancer efficacy, safety, tissue distribution and pharmacodynamic biomarkers will likely be relevant for human translation.ClinicalTrials.gov NCT02114957.

  17. Safety, tolerability, and efficacy of a fixed-dose combination of olmesartan 40 mg and hydrochlorothiazide 12.5/25 mg in daily practice

    Directory of Open Access Journals (Sweden)

    Bramlage P

    2013-08-01

    Full Text Available Peter Bramlage,1 Claudia Zemmrich,1 Reinhard Ketelhut,2 Wolf-Peter Wolf,3 Eva-Maria Fronk,4 Roland E Schmieder5 1Institut für Pharmakologie und Präventive Medizin, Mahlow, Germany; 2Institut für Sportmedizin, Universitätsklinikum Charité, Humboldt Universität zu Berlin, Berlin, Germany; 3Daiichi Sankyo Deutschland GmbH, Munich, Germany; 4Daiichi Sankyo Europe GmbH, Munich, Germany; 5Universitätsklinikum Erlangen, Klinik für Nephrologie und Hypertensiologie, Erlangen, Germany Background: The safety and efficacy of olmesartan 40 mg and hydrochlorothiazide (HCTZ as a fixed-dose combination has been investigated in clinical trials leading to its approval. The aims of the present study were to confirm these data in an unselected patient population in daily practice and to determine the impact of physical activity on blood pressure control. Methods: In a multicenter, noninterventional study, 3,333 patients with either insufficient blood pressure control on olmesartan 40 mg alone or on a fixed/free combination of olmesartan 40 mg and HCTZ 12.5/25 mg were primarily assessed for safety and tolerability of the fixed-dose combination of olmesartan 40 mg and HCTZ 12.5/25 mg at 24 ± 2 weeks. Secondary objectives were blood pressure reduction, treatment compliance, and impact of physical activity as measured by the sum of weekly energy costs. Results: The mean patient age was 63.2 ± 11.46 years, mean baseline blood pressure was 159.6 ± 15.28/93.5 ± 9.52 mmHg, and 70.9% had at least one additional cardiovascular risk factor. Adverse drug reactions were rare (n = 19, and no serious adverse drug reactions occurred. Compliance with drug therapy was at least sufficient in more than 99% of patients at the end of the study. Blood pressure at the last available visit was reduced by 26.1 ± 15.5/13.0 ± 10.1 mmHg versus baseline (P < 0.0001, but had reduced effectiveness in patients ≥75 years with diabetes or impaired renal function. In 69% of patients

  18. A Flexible-Dose Study of Paliperidone ER in Patients With Nonacute Schizophrenia Previously Treated Unsuccessfully With Oral Olanzapine.

    Science.gov (United States)

    Kotler, Moshe; Dilbaz, Nesrin; Rosa, Fernanda; Paterakis, Periklis; Milanova, Vihra; Smulevich, Anatoly B; Lahaye, Marjolein; Schreiner, Andreas

    2016-01-01

    The goal of this study was to explore the tolerability, safety, and treatment response of switching from oral olanzapine to paliperidone extended release (ER). Adult patients with nonacute schizophrenia who had been treated unsuccessfully with oral olanzapine were switched to flexible doses of paliperidone ER (3 to 12 mg/d). The primary efficacy outcome was a ≥ 20% improvement in Positive and Negative Syndrome Scale (PANSS) total scores from baseline to endpoint for patients who switched medications because of lack of efficacy with olanzapine and noninferiority versus previous olanzapine treatment (mean endpoint change in PANSS total scores vs. baseline of ≤ 5 points) for patients who switched for reasons other than lack of efficacy. Safety and tolerability were assessed by monitoring adverse events, extrapyramidal symptoms, and weight change. Of 396 patients, 65.2% were men, mean age was 40.0 ± 12.0 years, and 75.5% had paranoid schizophrenia. Among the patients whose main reason for switching was lack of efficacy, an improvement in the PANSS total score of ≥ 20% occurred in 57.4% of patients. Noninferiority was confirmed for each subgroup of patients whose main reason for switching was something other than lack of efficacy. Paliperidone ER was generally well tolerated. Extrapyramidal symptoms as measured by total Extrapyramidal Symptom Rating Scale scores showed statistically significant and clinically relevant improvements at endpoint, the average weight decreased by 0.8 ± 5.2 kg at endpoint, and a clinically relevant weight gain of ≥ 7% occurred in 8.0% of patients. Paliperidone ER flexibly-dosed over 6 months was well tolerated and associated with a meaningful clinical response in patients with nonacute schizophrenia who had previously been unsuccessfully treated with oral olanzapine.

  19. Risk Factors and Dose-Effect Relationship for Mandibular Osteoradionecrosis in Oral and Oropharyngeal Cancer Patients

    International Nuclear Information System (INIS)

    Lee, Ik Jae; Koom, Woong Sub; Lee, Chang Geol; Kim, Yong Bae; Yoo, Sei Whan; Keum, Ki Chang; Kim, Gwi Eon; Choi, Eun Chang; Cha, In Ho

    2009-01-01

    Purpose: To analyze risk factors and the dose-effect relationship for osteoradionecrosis (ORN) of the mandible after radiotherapy of oral and oropharyngeal cancers. Materials and Methods: One-hundred ninety-eight patients with oral (45%) and oropharyngeal cancer (55%) who had received external radiotherapy between 1990 and 2000 were retrospectively reviewed. All patients had a dental evaluation before radiotherapy. The median radiation dose was 60 Gy (range, 16-75 Gy), and the median biologically effective dose for late effects (BED late ) in bone was 114 Gy 2 (range, 30-167 Gy 2 ). Results: The frequency of ORN was 13 patients (6.6%). Among patients with mandibular surgery, eight had ORN at the surgical site. Among patients without mandibular surgery, five patients had ORN on the molar area of the mandible. The median time to ORN was 22 months (range, 1-69 months). Univariate analysis revealed that mandibular surgery and Co-60 were significant risk factors for ORN (p = 0.01 and 0.04, respectively). In multivariate analysis, mandibular surgery was the most important factor (p = 0.001). High radiation doses over BED 102.6 Gy 2 (conventional dose of 54 Gy at 1.8 Gy/fraction) were also a significant factor for ORN (p = 0.008) and showed a positive dose-effect relationship in logistic regression (p = 0.04) for patients who had undergone mandibular surgery. Conclusions: Mandibular surgery was the most significant risk factor for ORN of mandible in oral and oropharyngeal cancers patients. A BED of 102.6 Gy 2 or higher to the mandible also significantly increases the risk of ORN.

  20. A randomized comparative trial of two low-dose oral isotretinoin regimens in moderate to severe acne vulgaris

    Science.gov (United States)

    Dhaked, Daulat Ram; Meena, Ram Singh; Maheshwari, Anshul; Agarwal, Uma Shankar; Purohit, Saroj

    2016-01-01

    Background: Oral isotretinoin is highly effective in all forms and grades of acne, even in lower dosages (acne vulgaris. Materials and Methods: A total of 240 patients with moderate to severe acne vulgaris were selected and randomized into two groups and treated with a fixed dose of 20 mg of isotretinoin (Group A - daily and Group B - alternate days) for 24 weeks and followed up for 12 weeks post therapy. Results: A total of 234 patients completed the study. At the end of therapy, decrease in the total acne loads up to 98.99% (Group A) and 97.69% (Group B) was achieved from the baseline (P acne, Group A performed significantly better than Group B until the end of 36 weeks. While in the moderate acne, significant difference in the response between both groups was observed only up to 12 weeks. No serious side effect was observed. Conclusion: Both isotretinoin regimens were well tolerated and found to be an effective treatment for moderate to severe acne vulgaris. However, in moderate acne 20 mg alternate day regimen may be preferred. A 20 mg daily regimen is a better choice for severe acne in terms of response. Limitation: Small sample size and short follow-up period. PMID:27730033

  1. Oral dosing of chemical indicators for in vivo monitoring of Ca2+ dynamics in insect muscle.

    Directory of Open Access Journals (Sweden)

    Ferdinandus

    Full Text Available This paper proposes a remarkably facile staining protocol to visually investigate dynamic physiological events in insect tissues. We attempted to monitor Ca2+ dynamics during contraction of electrically stimulated living muscle. Advances in circuit miniaturization and insect neuromuscular physiology have enabled the hybridization of living insects and man-made electronic components, such as microcomputers, the result of which has been often referred as a Living Machine, Biohybrid, or Cyborg Insect. In order for Cyborg Insects to be of practical use, electrical stimulation parameters need to be optimized to induce desired muscle response (motor action and minimize the damage in the muscle due to the electrical stimuli. Staining tissues and organs as well as measuring the dynamics of chemicals of interest in muscle should be conducted to quantitatively and systematically evaluate the effect of various stimulation parameters on the muscle response. However, existing staining processes require invasive surgery and/or arduous procedures using genetically encoded sensors. In this study, we developed a non-invasive and remarkably facile method for staining, in which chemical indicators can be orally administered (oral dosing. A chemical Ca2+ indicator was orally introduced into an insect of interest via food containing the chemical indicator and the indicator diffused from the insect digestion system to the target muscle tissue. We found that there was a positive relationship between the fluorescence intensity of the indicator and the frequency of electrical stimulation which indicates the orally dosed indicator successfully monitored Ca2+ dynamics in the muscle tissue. This oral dosing method has a potential to globally stain tissues including neurons, and investigating various physiological events in insects.

  2. Oral dosing of chemical indicators for in vivo monitoring of Ca2+ dynamics in insect muscle.

    Science.gov (United States)

    Ferdinandus; Arai, Satoshi; Ishiwata, Shin'ichi; Suzuki, Madoka; Sato, Hirotaka

    2015-01-01

    This paper proposes a remarkably facile staining protocol to visually investigate dynamic physiological events in insect tissues. We attempted to monitor Ca2+ dynamics during contraction of electrically stimulated living muscle. Advances in circuit miniaturization and insect neuromuscular physiology have enabled the hybridization of living insects and man-made electronic components, such as microcomputers, the result of which has been often referred as a Living Machine, Biohybrid, or Cyborg Insect. In order for Cyborg Insects to be of practical use, electrical stimulation parameters need to be optimized to induce desired muscle response (motor action) and minimize the damage in the muscle due to the electrical stimuli. Staining tissues and organs as well as measuring the dynamics of chemicals of interest in muscle should be conducted to quantitatively and systematically evaluate the effect of various stimulation parameters on the muscle response. However, existing staining processes require invasive surgery and/or arduous procedures using genetically encoded sensors. In this study, we developed a non-invasive and remarkably facile method for staining, in which chemical indicators can be orally administered (oral dosing). A chemical Ca2+ indicator was orally introduced into an insect of interest via food containing the chemical indicator and the indicator diffused from the insect digestion system to the target muscle tissue. We found that there was a positive relationship between the fluorescence intensity of the indicator and the frequency of electrical stimulation which indicates the orally dosed indicator successfully monitored Ca2+ dynamics in the muscle tissue. This oral dosing method has a potential to globally stain tissues including neurons, and investigating various physiological events in insects.

  3. Effects of monophasic low-dose oral contraceptives on fibrin formation and resolution in young women

    DEFF Research Database (Denmark)

    Petersen, K R; Sidelmann, Johannes Jakobsen; Skouby, S O

    1993-01-01

    OBJECTIVE: The purpose of this study was to examine key variables in the regulation of coagulation and fibrinolysis during intake of low-dose oral contraceptives containing newly developed progestogens. STUDY DESIGN: Thirty-four healthy young women were allocated to 12 consecutive cycles of treat......OBJECTIVE: The purpose of this study was to examine key variables in the regulation of coagulation and fibrinolysis during intake of low-dose oral contraceptives containing newly developed progestogens. STUDY DESIGN: Thirty-four healthy young women were allocated to 12 consecutive cycles...... and concentration of plasminogen activator inhibitor. Thrombin-antithrombin III complexes and fibrin degradation products were unchanged, signifying no effect of hormonal intake on the degree of activation of the coagulation system or the efficacy of fibrinolysis. CONCLUSION: The overall dynamic balance between...

  4. Time, dose and volume factors in interstitial brachytherapy combined with external irradiation for oral tongue carcinoma

    International Nuclear Information System (INIS)

    Yorozu, Atsunori

    1996-01-01

    This is a retrospective analysis of 136 patients with squamous cell carcinoma of stages I and II of the oral tongue who were treated with interstitial brachytherapy alone or in combination with external irradiation between 1976 and 1991. Control of the primary lesion and the occurrence of late complications were analyzed with respect to dose, time and tumor size with the Cox hazard model. The 5-year survival rates for stages I and II were 84.5% and 75.6%. The 5-year primary control rate was 91.3% for stage I and 77.3% for stage II (p 50 Gy compared with a brachytherapy dose 30 mm. Late complications should be reduced by using a spacer, improvements in dental and oral hygiene, and a sophisticated implant method. (author)

  5. Whole-body dose and energy measurements in radiotherapy by a combination of LiF:Mg,Cu,P and LiF:Mg,Ti.

    Science.gov (United States)

    Hauri, Pascal; Schneider, Uwe

    2018-04-01

    Long-term survivors of cancer who were treated with radiotherapy are at risk of a radiation-induced tumor. Hence, it is important to model the out-of-field dose resulting from a cancer treatment. These models have to be verified with measurements, due to the small size, the high sensitivity to ionizing radiation and the tissue-equivalent composition, LiF thermoluminescence dosimeters (TLD) are well-suited for out-of-field dose measurements. However, the photon energy variation of the stray dose leads to systematic dose errors caused by the variation in response with radiation energy of the TLDs. We present a dosimeter which automatically corrects for the energy variation of the measured photons by combining LiF:Mg,Ti (TLD100) and LiF:Mg,Cu,P (TLD100H) chips. The response with radiation energy of TLD100 and TLD100H compared to 60 Co was taken from the literature. For the measurement, a TLD100H was placed on top of a TLD100 chip. The dose ratio between the TLD100 and TLD100H, combined with the ratio of the response curves was used to determine the mean energy. With the energy, the individual correction factors for TLD100 and TLD100H could be found. The accuracy in determining the in- and out-of-field dose for a nominal beam energy of 6MV using the double-TLD unit was evaluated by an end-to-end measurement. Furthermore, published Monte Carlo (M.C.) simulations of the mean photon energy for brachytherapy sources, stray radiation of a treatment machine and cone beam CT (CBCT) were compared to the measured mean energies. Finally, the photon energy distribution in an Alderson phantom was measured for different treatment techniques applied with a linear accelerator. Additionally, a treatment plan was measured with a cobalt machine combined with an MRI. For external radiotherapy, the presented double-TLD unit showed a relative type A uncertainty in doses of -1%±2% at the two standard deviation level compared to an ionization chamber. The type A uncertainty in dose was in

  6. Placental transfer, disposition, and metabolism of a single oral dose of [14CH3S] methamidophos in Sprague Dawley rat

    International Nuclear Information System (INIS)

    Salama, A.K.; Bakry, N.M.; Aly, H.A.; Abou-Donia, M.B.

    1990-01-01

    A single oral dose of 8 mg/kg (8 μci/kg) of [ 14 CH 3 S]methamidophos was administered on day 18 of gestation to pregnant Sprague Dawley rats. Eight groups of three rats were killed after 10 min. and 0.5, 1, 3, 6, 12, 24, 48 hr. At termination, 27.10% of the radioactivity was excreted in the urine, but only 4.19% of the dose was recovered in the feces. Also, 24.59% was recovered as 14 CO 2 , while only 0.11% was detected in expired air as volatile materials. Radiolabeled material was rapidly absorbed and distributed in the tissues with levels in most tissues peaking at one hour. A total of 1.73% of the dose was recovered in the fetus. Methamidophos and its metabolites were analyzed by gas-liquid chromatography/mass spectrometry, thin-layer chromatography and liquid scintillation counting. Methamidophos disappeared biexponentially from tissues and the fetus. The terminal half-lives of methamidophos were 94 and 13.5 hr for plasma and fetus, respectively. The major metabolites in the tissues were monomethyl phosphoramidate and monomethyl phosphate. In addition to these metabolites, phosphoric acid was found in the liver, kidneys, lung, uterus, fetus and urine

  7. Missed doses of oral antihyperglycemic medications in US adults with type 2 diabetes mellitus: prevalence and self-reported reasons.

    Science.gov (United States)

    Vietri, Jeffrey T; Wlodarczyk, Catherine S; Lorenzo, Rose; Rajpathak, Swapnil

    2016-09-01

    Adherence to antihyperglycemic medication is thought to be suboptimal, but the proportion of patients missing doses, the number of doses missed, and reasons for missing are not well described. This survey was conducted to estimate the prevalence of and reasons for missed doses of oral antihyperglycemic medications among US adults with type 2 diabetes mellitus, and to explore associations between missed doses and health outcomes. The study was a cross-sectional patient survey. Respondents were contacted via a commercial survey panel and completed an on-line questionnaire via the Internet. Respondents provided information about their use of oral antihyperglycemic medications including doses missed in the prior 4 weeks, personal characteristics, and health outcomes. Weights were calculated to project the prevalence to the US adult population with type 2 diabetes mellitus. Outcomes were compared according to number of doses missed in the past 4 weeks using bivariate statistics and generalized linear models. Approximately 30% of adult patients with type 2 diabetes mellitus reported missing or reducing ≥1 dose of oral antihyperglycemic medication in the prior 4 weeks. Accidental missing was more commonly reported than purposeful skipping, with forgetting the most commonly reported reason. The timing of missed doses suggested respondents had also forgotten about doses missed, so the prevalence of missed doses is likely higher than reported. Outcomes were poorer among those who reported missing three or more doses in the prior 4 weeks. A substantial number of US adults with type 2 diabetes mellitus miss doses of their oral antihyperglycemic medications.

  8. Concentrations of tylvalosin and 3-O-acetyltylosin attained in the synovial fluid of swine after administration by oral gavage at 50 and 5 mg/kg.

    Science.gov (United States)

    Canning, P; Bates, J; Hammen, K; Coetzee, J; Wulf, L; Rajewski, S; Wang, C; Karriker, L

    2016-12-01

    The objectives of this study were to determine the concentration of tylvalosin (TVN) and its metabolite, 3-O-acetyltylosin (3AT) in the synovial fluid of growing pigs when administered as a single bolus by oral gavage at target doses of 50 mg/kg (Trial 1) and 5 mg/kg (Trial 2). TVN is a water soluble macrolide antimicrobial used in swine production. The stability of the drug in synovial fluid samples stored at -70 °C up to 28 days was also evaluated in Trial 2. In Trial 1, eight pigs were randomly assigned to one of eight time points for euthanasia and synovial fluid collection: 0, 1, 2, 3, 4, 6, 9, 12 h postgavage. For Trial 2, 24 pigs were randomly allocated to one terminal collection time point at 0, 2, 4, 6, 8 or 10 h postgavage. Synovial fluid was analyzed to determine TVN and 3AT concentrations. TVN and 3AT were detected in Trial 1 at all time points, except 0 h. At 2 h postgavage for trial 2, the mean concentrations peaked at 31.17 ng/mL (95% CI: 18.62-52.16) for TVN and at 58.82 ng/mL (95% CI: 35.14-98.46) for 3AT. Storage duration did not impact TVN or 3AT concentrations (P-value 0.9732). © 2016 John Wiley & Sons Ltd.

  9. Role of oral tramadol 50 mg in reducing pain associated with outpatient hysteroscopy: A randomised double-blind placebo-controlled trial.

    Science.gov (United States)

    Hassan, AbdelGany; Haggag, Hisham

    2016-02-01

    Several drugs have been used to reduce hysteroscopy-associated pain. Although the Royal College of Obstetricians and Gynaecologists has recommended against the use of opiates in outpatient hysteroscopy, we wished to investigate if opioids can be used if the appropriate opioid was given in the appropriate dose. To study the effectiveness of tramadol 50 mg in reducing pain associated with outpatient hysteroscopy. A prospective randomised double-blind placebo-controlled trial conducted in the outpatient hysteroscopy clinic at Cairo University Hospital. Main outcome measures were the severity of pain during the procedure, immediately after the procedure and 30 minutes later assessed by a visual analogue scale (VAS). VAS of 0 indicates no pain and VAS of 10 indicates the worst possible pain. A total of 140 women who had diagnostic outpatient hysteroscopy were randomised to receive oral tramadol 50 mg or placebo one h before performing outpatient hysteroscopy. There was no difference between the groups in the age, parity, duration of the procedures or indications of hysteroscopy. The median pain score was significantly lower in the tramadol group during the procedure (5 vs 6; P = 0.013), immediately after the procedure (3 vs 4; P pain evoked by the procedure and the drug was well tolerated by women. © 2016 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

  10. Antimalarial iron chelator, FBS0701, shows asexual and gametocyte Plasmodium falciparum activity and single oral dose cure in a murine malaria model.

    Directory of Open Access Journals (Sweden)

    Patricia Ferrer

    Full Text Available Iron chelators for the treatment of malaria have proven therapeutic activity in vitro and in vivo in both humans and mice, but their clinical use is limited by the unsuitable absorption and pharmacokinetic properties of the few available iron chelators. FBS0701, (S3"-(HO-desazadesferrithiocin-polyether [DADFT-PE], is an oral iron chelator currently in Phase 2 human studies for the treatment of transfusional iron overload. The drug has very favorable absorption and pharmacokinetic properties allowing for once-daily use to deplete circulating free iron with human plasma concentrations in the high µM range. Here we show that FBS0701 has inhibition concentration 50% (IC(50 of 6 µM for Plasmodium falciparum in contrast to the IC(50 for deferiprone and deferoxamine at 15 and 30 µM respectively. In combination, FBS0701 interfered with artemisinin parasite inhibition and was additive with chloroquine or quinine parasite inhibition. FBS0701 killed early stage P. falciparum gametocytes. In the P. berghei Thompson suppression test, a single dose of 100 mg/kg reduced day three parasitemia and prolonged survival, but did not cure mice. Treatment with a single oral dose of 100 mg/kg one day after infection with 10 million lethal P. yoelii 17XL cured all the mice. Pretreatment of mice with a single oral dose of FBS0701 seven days or one day before resulted in the cure of some mice. Plasma exposures and other pharmacokinetics parameters in mice of the 100 mg/kg dose are similar to a 3 mg/kg dose in humans. In conclusion, FBS0701 demonstrates a single oral dose cure of the lethal P. yoelii model. Significantly, this effect persists after the chelator has cleared from plasma. FBS0701 was demonstrated to remove labile iron from erythrocytes as well as enter erythrocytes to chelate iron. FBS0701 may find clinically utility as monotherapy, a malarial prophylactic or, more likely, in combination with other antimalarials.

  11. Effect of a low dose combined oral contraceptive pill on the hormonal profile and cycle outcome following COS with a GnRH antagonist protocol in women over 35 years old.

    Science.gov (United States)

    Bakas, Panagiotis; Hassiakos, Dimitrios; Grigoriadis, Charalampos; Vlahos, Nikolaos F; Liapis, Angelos; Creatsas, George

    2014-11-01

    This prospective study examines if pre-treatment with two different doses of an oral contraceptive pill (OCP) modifies significantly the hormonal profile and/or the IVF/ICSI outcome following COS with a GnRH antagonist protocol. Infertile patients were allocated to receive either OCP containing 0.03 mg of ethinylestradiol and 3 mg of drospirenone, or OCP containing 0.02 mg of ethinylestradiol and 3 mg of drospirenone prior to initiation of controlled ovarian stimulation (COS) with recombinant gonadotropins on a variable multi-dose antagonist protocol (Ganirelix), while the control group underwent COS without OCP pretreatment. Lower dose OCP was associated with recovery of FSH on day 3 instead of day 5, but the synchronization of the follicular cohort, the number of retrieved oocytes and the clinical pregnancy rate were similar to higher dose OCP.

  12. Detection of sub micro Gray dose levels using OSL phosphor LiMgPO_4:Tb,B

    International Nuclear Information System (INIS)

    Rawat, N.S.; Dhabekar, Bhushan; Muthe, K.P.; Koul, D.K.; Datta, D.

    2017-01-01

    Highlights: • LiMgPO4:Tb,B has been studied and shown to possesses minimum measurable dose (MMD) in sub micro Gray region. • MMD as low as 0.49 µGy in readout time of less than 1 s at stimulation intensity of 32 mW/cm"2 has been achieved. • The OSL measurements for low doses has strengthened and validated this claim. • OSL spectrum shows several emission peaks and the prominent peak around 380 nm. - Abstract: Detection of sub micro Gray doses finds application in personnel and environmental monitoring, and nuclear forensics. Recently developed LiMgPO_4:Tb,B (LMP) is highly sensitive Optically Stimulated Luminescence (OSL) phosphor with excellent dosimetric properties. The OSL emission spectrum of LMP consists of several peaks attributed to characteristic Tb"3"+ emission. The OSL emission peak at 380 nm is favorable for bi-alkali PMT used in RISO reader system. It is demonstrated that significant improvement in dose detection threshold can be realized for LMP by optimization of continuous wave (CW–) OSL parameters like stimulation intensity and readout time. The minimum measurable dose (MMD) as low as 0.49 µGy in readout time of less than 1 s at stimulation intensity of 32 mW/cm"2 has been achieved using this phosphor. The recommendations for choice of parameters for personnel and environmental monitoring are also discussed.

  13. Detection of sub micro Gray dose levels using OSL phosphor LiMgPO{sub 4}:Tb,B

    Energy Technology Data Exchange (ETDEWEB)

    Rawat, N.S., E-mail: naru@barc.gov.in [Radiological Physics and Advisory Division, Bhabha Atomic Research Centre, Trombay, Mumbai (India); Dhabekar, Bhushan [Radiological Physics and Advisory Division, Bhabha Atomic Research Centre, Trombay, Mumbai (India); Muthe, K.P. [Technical Physics Division, Bhabha Atomic Research Centre, Trombay, Mumbai (India); Koul, D.K.; Datta, D. [Radiological Physics and Advisory Division, Bhabha Atomic Research Centre, Trombay, Mumbai (India)

    2017-04-15

    Highlights: • LiMgPO4:Tb,B has been studied and shown to possesses minimum measurable dose (MMD) in sub micro Gray region. • MMD as low as 0.49 µGy in readout time of less than 1 s at stimulation intensity of 32 mW/cm{sup 2} has been achieved. • The OSL measurements for low doses has strengthened and validated this claim. • OSL spectrum shows several emission peaks and the prominent peak around 380 nm. - Abstract: Detection of sub micro Gray doses finds application in personnel and environmental monitoring, and nuclear forensics. Recently developed LiMgPO{sub 4}:Tb,B (LMP) is highly sensitive Optically Stimulated Luminescence (OSL) phosphor with excellent dosimetric properties. The OSL emission spectrum of LMP consists of several peaks attributed to characteristic Tb{sup 3+} emission. The OSL emission peak at 380 nm is favorable for bi-alkali PMT used in RISO reader system. It is demonstrated that significant improvement in dose detection threshold can be realized for LMP by optimization of continuous wave (CW–) OSL parameters like stimulation intensity and readout time. The minimum measurable dose (MMD) as low as 0.49 µGy in readout time of less than 1 s at stimulation intensity of 32 mW/cm{sup 2} has been achieved using this phosphor. The recommendations for choice of parameters for personnel and environmental monitoring are also discussed.

  14. Formulation design of oral pediatric Acetazolamide suspension: dose uniformity and physico-chemical stability study.

    Science.gov (United States)

    Santoveña, Ana; Suárez-González, Javier; Martín-Rodríguez, Cristina; Fariña, José B

    2017-03-01

    The formulation of an active pharmaceutical ingredient (API) as oral solution or suspension in pediatrics is a habitual practice, due to the non-existence of many commercialized medicines in pediatric doses. It is also the simplest way to prepare and administer them to this vulnerable population. The design of a formulation that assures the dose and the system stability depends on the physico-chemical properties of the API. In this study, we formulate a class IV API, Acetazolamide (AZM) as suspension for oral administration to pediatric population. The suspension must comply attributes of quality, safety and efficacy for this route of administration. We use simple compounding procedures, as well as fewer pure excipients, as recommended for children. Mass and uniformity content assays and physical and chemical stability studies were performed. To quantify the API an UPLC method was used. We verified the physico-chemical stability of the suspensions and that they passed the mass test of the European Pharmacopeia (EP), but not the dose uniformity test. This reveals that AZM must be formulated as liquid forms with a more complex system of excipients (not usually indicated in pediatrics), or otherwise solid forms capable of assuring uniformity of mass and dose for every dosage unit.

  15. Estimates of dose to systematic organs and GI tract based on data from miniature swine orally intubated with a single dose of Am-241 citrate

    International Nuclear Information System (INIS)

    Bernard, S.R.; Nestor, C.W. Jr.; Eisele, G.R.; Eckerman, K.F.

    1982-01-01

    A model is presented for the internal radiation dose to the small intestine wall of miniature swine given Americium 241 citrate by oral intubation. The model incorporates the uptake of the Am-241 by the intestinal wall. About equal contributions of dose to the small intestine were observed from the intestinal contents and the wall itself

  16. Tratamento da esquitossomose mansoni pela oxamniquine em dose única, pela via oral

    Directory of Open Access Journals (Sweden)

    Aluizio Prata

    1976-06-01

    Full Text Available A oxamniquine em cápsulas foi usada no tratamento de 132 doentes com esquistossomose mansoni crônica, sendo 129 com a forma hepato-intestinal e 3 com a forma hepato-esplênica. A dose foi de 10 mg por quilo de peso corporal em 34 pacientes, 12.5 mg em 35 e 15 mg em 63. A tolerância foi excelente em 43,2% dos tratados, boa em 48,5% e satisfatória em 8,3%. As queixas mais freqüentes foram tonturas e sonolência, que aparecem logo após a ingestão da droga e são fugazes. Os exames de laboratório mostraram em um ou outro paciente somente discreta retenção de bromosulfaleina, aumento de transaminase e da bilirrubina, insuficientes para caracterizar uma hepatoxicidade evidente. O seguimento dos pacientes se prolongou por mais de quatro meses e constou de pelo menos cinco exames de fezes pelo método de sedimentação. Todos os exames foram negativos em 20 (66,66% pacientes que tomaram 10 mg, em 13 (56,52% que tomaram 12.5 mg e em 41 (89,13% que tomaram 15 mg. Excluindo-se os menores de 16 anos subiu a 95% a negatividade entre os que foram tratados com 15 mg.Oxamniquine in capsules was used in the treatment of 132 patients with chronic Schistosoma mansoni infections. 129 having the hepato intestinal form and 3 the hepato splenic form. The dose was 10mg per kiio body weight in 34 patients, 12.5mg in 35 and 15mg ip 63. The tolerance was excellent in 43.2% of those treated, good in 48.5% and satisfactory in 8.3%. The most frequent complaints were dizziness and somnolence which appear soon after ingestion and was transitory. Laboratory investigations showed in a few patients bromosutphalein retention, raised transaminases or biiirubin but insufficient to constitute hepatoxicity. The follow-up of the patients continued for more than 4 months and consisted of five or more examinations by a sedimentation method. AH the examinations were negative in 20 (66.66% patients who took lOmg, in 13 (56.52% who took 12.5mg and in 41 (89.13% who took 15mg

  17. A single 2 g oral dose of extended-release azithromycin for treatment of gonococcal urethritis.

    Science.gov (United States)

    Yasuda, Mitsuru; Ito, Shin; Kido, Akira; Hamano, Kiminari; Uchijima, Yutaka; Uwatoko, Noriyasu; Kusuyama, Hiroyuki; Watanabe, Akiko; Miyamura, Ryuzou; Miyata, Kazutoyo; Deguchi, Takashi

    2014-11-01

    We treated gonococcal urethritis in men with a single 2 g dose of azithromycin extended-release formulation (azithromycin-SR) to determine its microbiological outcomes and tolerability. We enrolled 189 Japanese men with gonococcal urethritis between April 2009 and December 2013. The patients were given a single 2 g dose of azithromycin-SR. Microbiological efficacy was evaluated by the results of the post-treatment molecular testing of Neisseria gonorrhoeae. MIC testing was performed only for pretreatment isolates of N. gonorrhoeae collected from the patients. We evaluated 130 patients for microbiological outcomes. Of these patients, 122 (93.8%) were judged to be microbiologically cured on the basis of negative test results. All isolates for which the azithromycin MICs were ≤0.25 mg/L were eradicated, whereas 5 of 12 isolates for which the MICs were 1 mg/L persisted after the treatment. Forty-six adverse events occurred in 41 patients. However, all adverse events were classified as mild. The eradication rate of N. gonorrhoeae was 93.8% in men with gonococcal urethritis treated with a single 2 g dose of azithromycin-SR. The breakpoint MIC of a 2 g dose of azithromycin-SR for gonococcal urethritis associated with clinical treatment failures appeared to be 1 mg/L. With regard to side effects of higher doses of azithromycin, the 2 g dose of azithromycin-SR appeared to improve tolerability. However, the widespread use of a high-dose regimen of azithromycin might lead to the development of further resistance to azithromycin. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  18. Comparison of distribution and toxicity following repeated oral dosing of different vanadium oxide nanoparticles in mice

    Energy Technology Data Exchange (ETDEWEB)

    Park, Eun-Jung, E-mail: pejtoxic@hanmail.net [Myunggok Eye Research Institute, Konyang University, Daejeon 302-718 (Korea, Republic of); Lee, Gwang-Hee [School of Civil, Environmental, and Architectural Engineering, Korea University, Seoul 136-713 (Korea, Republic of); Yoon, Cheolho [Seoul Center, Korea Basic Science Institute, Seoul 126-16 (Korea, Republic of); Kim, Dong-Wan, E-mail: dwkim1@korea.ac.kr [School of Civil, Environmental, and Architectural Engineering, Korea University, Seoul 136-713 (Korea, Republic of)

    2016-10-15

    Vanadium is an important ultra-trace element derived from fuel product combustion. With the development of nanotechnology, vanadium oxide nanoparticles (VO NPs) have been considered for application in various fields, thus the possibility of release into the environment and human exposure is also increasing. Considering that verification of bioaccumulation and relevant biological responses are essential for safe application of products, in this study, we aimed to identify the physicochemical properties that determine their health effects by comparing the biological effects and tissue distribution of different types of VO NPs in mice. For this, we prepared five types of VO NPs, commercial (C)-VO{sub 2} and -V{sub 2}O{sub 5} NPs and synthetic (S)-VO{sub 2}, -V{sub 2}O{sub 3,} and -V{sub 2}O{sub 5} NPs. While the hydrodynamic diameter of the two types of C-VO NPs was irregular and impossible to measure, those of the three types of S-VO NPs was in the range of 125–170 nm. The S- and C-V{sub 2}O{sub 5} NPs showed higher dissolution rates compared to other VO NPs. We orally dosed the five types of VO NPs (70 and 210 μg/mouse, approximately 2 and 6 mg/kg) to mice for 28 days and compared their biodistribution and toxic effects. We found that S-V{sub 2}O{sub 5} and S-V{sub 2}O{sub 3} NPs more accumulated in tissues compared to other three types of VO NPs, and the accumulated level was in order of heart>liver>kidney>spleen. Additionally, tissue levels of redox reaction-related elements and electrolytes (Na{sup +}, K{sup +}, and Ca{sup 2+}) were most clearly altered in the heart of treated mice. Notably, all S- and C-VO NPs decreased the number of WBCs at the higher dose, while total protein and albumin levels were reduced at the higher dose of S-V{sub 2}O{sub 5} and S-V{sub 2}O{sub 3} NPs. Taken together, we conclude that the biodistribution and toxic effects of VO NPs depend on their dissolution rates and size (surface area). Additionally, we suggest that further studies

  19. Long-term high-dose oral morphine in phantom limb pain with no addiction risk

    Directory of Open Access Journals (Sweden)

    Vinod Kumar

    2015-01-01

    Full Text Available Chronic phantom limb pain (PLP is a type of neuropathic pain, which is located in the missing/amputated limb. Phantom pain is difficult to treat as the exact basis of pain mechanism is still unknown. Various methods of treatment for PLP have been described, including pharmacological (NSAIDs, opioids, antiepileptic, antidepressants and non-pharmacological (TENS, sympathectomy, deep brain stimulation and motor cortex stimulation. Opioids are used for the treatment of neuropathic pain and dose of opioid is determined based on its effect and thus there is no defined ceiling dose for opioids. We report a case where a patient receiving high-dose oral morphine for chronic cancer pain did not demonstrate signs of addiction.

  20. Distribution of chloramphenicol to tissues, plasma and urine in pigs after oral intake of low doses.

    Science.gov (United States)

    Aspenström-Fagerlund, Bitte; Nordkvist, Erik; Törnkvist, Anna; Wallgren, Per; Hoogenboom, Ron; Berendsen, Bjorn; Granelli, Kristina

    2016-09-01

    Toxic effects of chloramphenicol in humans caused the ban for its use in food-producing animals in the EU. A minimum required performance level (MRPL) was specified for chloramphenicol at 0.3 μg kg(-1) for various matrices, including urine. In 2012, residues of chloramphenicol were found in pig urine and muscle without signs of illegal use. Regarding its natural occurrence in straw, it was hypothesised that this might be the source, straw being compulsory for use as bedding material for pigs in Sweden. Therefore, we investigated if low daily doses of chloramphenicol (4, 40 and 400 μg/pig) given orally during 14 days could result in residues in pig tissues and urine. A dose-related increase of residues was found in muscle, plasma, kidney and urine (showing the highest levels), but no chloramphenicol was found in the liver. At the lowest dose, residues were below the MRPL in all tissues except in the urine. However, in the middle dose, residues were above the MRPL in all tissues except muscle, and at the highest dose in all matrices. This study proves that exposure of pigs to chloramphenicol in doses occurring naturally in straw could result in residues above the MRPL in plasma, kidney and especially urine.

  1. Clinical outcome of high-dose-rate interstitial brachytherapy in patients with oral cavity cancer

    International Nuclear Information System (INIS)

    Lee, Sung Uk; Cho, Kwan Ho; Moon, Sung Ho; Choi, Sung Weon; Park, Joo Yong; Yun, Tak; Lee, Sang Hyun; Lim, Young Kyung; Jeong, Chi Young

    2014-01-01

    To evaluate the clinical outcome of high-dose-rate (HDR) interstitial brachytherapy (IBT) in patients with oral cavity cancer. Sixteen patients with oral cavity cancer treated with HDR remote-control afterloading brachytherapy using 192Ir between 2001 and 2013 were analyzed retrospectively. Brachytherapy was administered in 11 patients as the primary treatment and in five patients as salvage treatment for recurrence after the initial surgery. In 12 patients, external beam radiotherapy (50-55 Gy/25 fractions) was combined with IBT of 21 Gy/7 fractions. In addition, IBT was administered as the sole treatment in three patients with a total dose of 50 Gy/10 fractions and as postoperative adjuvant treatment in one patient with a total of 35 Gy/7 fractions. The 5-year overall survival of the entire group was 70%. The actuarial local control rate after 3 years was 84%. All five recurrent cases after initial surgery were successfully salvaged using IBT +/- external beam radiotherapy. Two patients developed local recurrence at 3 and 5 months, respectively, after IBT. The acute complications were acceptable (< or =grade 2). Three patients developed major late complications, such as radio-osteonecrosis, in which one patient was treated by conservative therapy and two required surgical intervention. HDR IBT for oral cavity cancer was effective and acceptable in diverse clinical settings, such as in the cases of primary or salvage treatment.

  2. Tratamento da esquitossomose mansoni pela oxamniquine em dose única, pela via oral

    Directory of Open Access Journals (Sweden)

    Aluizio Prata

    1976-06-01

    Full Text Available A oxamniquine em cápsulas foi usada no tratamento de 132 doentes com esquistossomose mansoni crônica, sendo 129 com a forma hepato-intestinal e 3 com a forma hepato-esplênica. A dose foi de 10 mg por quilo de peso corporal em 34 pacientes, 12.5 mg em 35 e 15 mg em 63. A tolerância foi excelente em 43,2% dos tratados, boa em 48,5% e satisfatória em 8,3%. As queixas mais freqüentes foram tonturas e sonolência, que aparecem logo após a ingestão da droga e são fugazes. Os exames de laboratório mostraram em um ou outro paciente somente discreta retenção de bromosulfaleina, aumento de transaminase e da bilirrubina, insuficientes para caracterizar uma hepatoxicidade evidente. O seguimento dos pacientes se prolongou por mais de quatro meses e constou de pelo menos cinco exames de fezes pelo método de sedimentação. Todos os exames foram negativos em 20 (66,66% pacientes que tomaram 10 mg, em 13 (56,52% que tomaram 12.5 mg e em 41 (89,13% que tomaram 15 mg. Excluindo-se os menores de 16 anos subiu a 95% a negatividade entre os que foram tratados com 15 mg.

  3. Desarrollo de la formulación de cefalexina 250 mg granulado para suspensión oral

    Directory of Open Access Journals (Sweden)

    Roxana Martínez Fernández

    2002-04-01

    Full Text Available Se desarrolló la formulación de la cefalexina 250 mg como granulado para suspensión oral. Se utilizó la vía húmeda para la preparación del granulado, teniendo en cuenta los resultados de la caracterización físico-química realizada a las materias primas empleadas. Los resultados de los análisis físico-químicos y microbiológicos del producto terminado fueron satisfactorios. Se realizó un estudio de estabilidad en vida de estante durante 18 meses, con el que se pudo comprobar que la formulación obtenida es estable durante el tiempo estudiado a temperatura entre 15 y 25 °C y durante 7 d después de reconstituido y mantenido en refrigeración. El medicamento cumple con las especificaciones de calidad descritas en la USP 24.The formulation of cephalexin 250 mg was developed as a granulate for oral suspension. The humid way was used for the preparation of the granulate, taking into account the results of the physicochemical characterization of the raw materials used. The results of the physicochemical and microbiological analyses of the finished product were satisfactory. A shelf life stability study was conducted for 18 months that made possible to prove that the formulation obtained was stable during the studied time at temperatures between 15 and 25 ºC and for 7 days after being reconstituted and kept in refrigeration. The drug meets the quality specifications described in the USP 24.

  4. [Pharmacokinetics and relative bioavailability of THC and THC-solid dispersion orally to mice at single dose].

    Science.gov (United States)

    Liao, Li; Hua, Hua; Zhao, Jun-Ning; Luo, Heng; Yang, An-Dong

    2014-03-01

    To establish a fast sensitive, reproducible LC-MS/MS method to study pharmacokinetic properties of THC, and compare relative bioavailability of THC and its solid dispersion in mice. 200 mice were divided randomly into two groups, and administered orally with THC and THC-solid dispersion after fasting (calculate on THC:400 mg x kg(-1)), used HPLC-MS/MS method to determine the THC concentration of each period at the following times: baseline ( predose ), 15, 30, 45 min, 1, 1.5, 2, 3, 4, 6, 24 h after dosing. Calculating the pharmacokinetic parameters according to the C-t curv, and then use the Phoenix WinNonlin software for data analysis. The calibration curves were linear over the range 9.06-972 microg x L(-1) for THC (R2 = 0.999). The limit of detection (LOD) was 0.7 microg x L(-1), respectively. The average extraction recoveries for THC was above 75%, The methodology recoveries were between 79% and 108%. The intra-day and inter-day RSD were less than 13%, the stability test showed that the plasma samples was stable under different conditions (RSD THC and THC-solid dispersion orally to mice shows as fllows: T(max), were 60 and 15 min, AUC(0-t) were 44 500.43 and 57 497.81 mg x L(-1) x min, AUC(0-infinity) were 51 226.00 and 68 031.48 mg x L(-1) x min, MRT(0-infinity) were 596.915 6, 661.747 7 min, CL(z)/F were 0.007 809 and 0.005 88 L x min(-1) x kg(-1). Compared with THC, the MRT and t1/2 of the THC-solid dispersion were all slightly extended, the t(max) was significantly reduced, AUC(0-24 h), AUC(0-infinity) and C(max) were all significantly higher, the relative bioavailability of THC-solid dispersion is 1.34 times of THC. The results of the experiment shows that the precision, accuracy, recovery and applicability were found to be adequate for the pharmacokinetic studies. After oral administration to mice, the relative bioavailability of THC-solid dispersion show significant improvement compared to THC.

  5. No Dose Adjustment is Recommended for Digoxin, Warfarin, Atorvastatin or a Combination Oral Contraceptive When Coadministered with Dulaglutide.

    Science.gov (United States)

    de la Peña, Amparo; Cui, Xuewei; Geiser, Jeanne; Loghin, Corina

    2017-11-01

    Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) for the treatment of type 2 diabetes mellitus are known to delay gastric emptying (GE). The potential effect of the GLP-1 RA dulaglutide on the pharmacokinetics (PK) of four orally administered drugs and on the pharmacodynamic (PD) effect of warfarin was investigated. In four separate clinical pharmacology studies, digoxin, warfarin, atorvastatin and Ortho-Cyclen ® were orally administered to healthy subjects with and without a subcutaneous dose of dulaglutide 1.5 mg. The effect of dulaglutide coadministration was assessed based on the PK parameters of key analytes. For warfarin PD, the effect of dulaglutide on the international normalized ratio (INR) was evaluated. Areas under the concentration-time curves (AUCs) with and without dulaglutide were similar for all analytes except atorvastatin, where it was reduced by 21%. Maximum concentrations (C max ) were generally lower following coadministration with dulaglutide, with statistically significant reductions (90% confidence intervals of geometric least squares means ratios outside 0.80-1.25) for all analytes except R-warfarin. For all analytes, there was a general trend for the time to C max (t max ) to increase following coadministration with dulaglutide. For warfarin, dulaglutide coadministration had no statistically significant effect on the maximum INR (INR max ); however, a 2% increase in area under the INR curve (AUC INR ) was observed. Dulaglutide did not affect the absorption of the tested medications to a clinically relevant degree. Based on the PK and PD evaluations, no dose adjustments for digoxin, warfarin, atorvastatin and Ortho-Cyclen ® are recommended when coadministered with dulaglutide. NCT01458210, NCT01436201, NCT01432938, and NCT01250834.

  6. Dose and risk evaluation to the thyroid gland in intra-oral dental radiology

    International Nuclear Information System (INIS)

    Souza, Edmilson M.; Lima, Marco A.F.; Kelecom, Alphonse; Correa, Samanda C.A.; Silva, Ademir X.; Brito, Alan

    2008-01-01

    Intra-oral technique is one of the most frequently used procedures of dental radiology, allowing the detection of a variety of dental anomalies such as caries, dental trauma and periodontal lesions, while exposing patients to relatively low doses of radiation. However, although the adverse effects of doses generated by dental radiology are essentially stochastic, a number of epidemiological studies have provided evidence of an increased risk of thyroid tumors for dental radiography. Many studies have measured doses of radiation for dental radiography, but only a few have estimated thyroid dose. Furthermore, most of the studies on dose evaluation in dental radiology are based on standardized calculation phantoms, which neglect the variance of the patient size or even sex. The purpose of this study is to use the Monte Carlo code MCNPX and the FAX (Female Adult voXel) and MAX (Male Adult voXel) phantoms to investigate how absorbed doses to the thyroid gland in intraoral dental examinations vary in female and male patients. The lifetime cancer incidence attributable to dental examinations were estimated using the Biological Effects of Ionizing Radiations (BEIR) VII Committee Report. The phantoms study proved a useful trial for detecting the radiation dose to the thyroid gland and conclusively supported that the anatomy may be regarded as an influencing factor in radiation dose received during dental examination. Finally, the results have also confirmed that the association of the MCNPX code and the MAX and FAX phantoms is very useful in dosimetric studies on radiographic examinations of female and male patients. (author)

  7. Reduced time for urinary alkalinization before high-dose methotrexate with preadmission oral bicarbonate.

    Science.gov (United States)

    Kintzel, Polly E; Campbell, Alan D; Yost, Kathleen J; Brinker, Brett T; Arradaza, Nicole V; Frobish, Daniel; Wehr, Alison M; O'Rourke, Timothy J

    2012-06-01

    Hydration and urinary alkalinization are essential for reducing renal dysfunction with high dose methotrexate (HDMTX). This report presents an analysis of institutional methods used to achieve adequate urinary alkalinization and output for patients receiving single agent HDMTX. Renal and metabolic parameters of tolerance were examined. Medical records of adult patients receiving HDMTX during the calendar years of 2008-2009 were retrospectively reviewed to determine the time to achieve urine pH > 7. Number of hospital days, bicarbonate dose, ordered hydration rate, urine output, and urine pH were assessed. A survival analysis model was run for time to urine pH > 7 using preadmission oral bicarbonate as a predictor variable and including a frailty term. Observational statistics were performed for other parameters. The analysis included 79 encounters for ten patients. Urine pH > 7 was achieved more rapidly in patients receiving preadmission oral bicarbonate (P = 0.012). The number of patients receiving HDMTX on the same day as admission was greater for those receiving preadmission oral bicarbonate (47%) in comparison to those who did not (2%), and they spent less time in the hospital. A standard regimen for hydration and urinary alkalinization based on this project is reported. The nature and frequency of adverse events were as expected for this treatment. At our institution, the time to achieve urinary alkalinization was reduced for patients receiving preadmission oral bicarbonate which facilitated chemotherapy infusion on the same day as admission and decreased the number of calendar days that patients stayed in the hospital.

  8. Effects of Tadalafil 5 mg Dosed Once Daily in Men with Premature Ejaculation.

    Science.gov (United States)

    Ozcan, Levent; Polat, Emre Can; Onen, Efe; Kocaaslan, Ramazan; Otunctemur, Alper; Cekmen, Mustafa; Eraldemir, Ceyla; Ozbek, Emin

    2017-01-01

    In this study, we evaluated the effect of 5 mg tadalafil once daily in men with premature ejaculation (PE). Thirty married men with lifelong PE and 30 healthy men as control group were included in this study. All the patients received 5 mg tadalafil once a day for a month. The international index of erectile function questionnaire and intravaginal ejaculatory latency times (IELTs) and PE profile were recorded before and after treatment. Plasma samples were collected before and after treatment. The mean baseline IELTs was 40.8 ± 8.1 s in the PE group and 196.5 ± 26.2 s in the control group. After treatment in the PE group, the mean IELTs values showed a statistically significant improvement from the baseline values. At the end of 4 weeks, in the PE group, the mean IELT values showed a statistically significant improvement from the baseline values. Baseline serum nitric oxide (NO) levels were 27.3 ± 1.7 in the PE group and in the 31.1 ± 1.4 healthy control groups. After treatment, NO levels were increased from baseline. We consider that 5 mg tadalafil once daily is safety and effective for the treatment of PE. © 2016 S. Karger AG, Basel.

  9. Repeated dose 90-day oral toxicity test of G-7% NANA in rats: An application of new criterion for toxicity determination to test article-induced changes.

    Science.gov (United States)

    Heo, Hye Seon; An, MinJi; Lee, Ji Sun; Kim, Hee Kyong; Park, Yeong-Chul

    2018-06-01

    G-7% NANA is N-acetylneuraminic acid(NANA) containing 7% sialic acid isolated from glycomacropeptide (GMP), a compound of milk. Since NANA is likely to have immunotoxicity, the need to ensure safety for long-term administration has been raised. In this study, a 90-day repeated oral dose toxicity test was performed in rats using G-7% NANA in the dosages of 0, 1250, 2500 and 5000 mg/kg/day.A toxicity determination criterion based on the significant change caused by the administration of the substancewas developed for estimating NOEL, NOAEL and LOAELapplied to this study. When analyzing the immunological markers, no significant changes were observed, even if other significant changes were observed in the high dose group. In accordance with the toxicity determination criterion developed, the NOEL in male and female has been determined as 2500 mg/kg/day, and the NOAEL in females has been determined as 5000 mg/kg/day. The toxicity determination criterion, applied for the first time in the repeated dose toxicity tests, could provide a basis for distinguishing NOEL and NOAEL more clearly; nevertheless, the toxicity determination criterion needs to be supplemented by adding differentiating adverse effects and non-adverse effects based on more experiences of the repeated dose toxicity tests. Copyright © 2018 Elsevier Inc. All rights reserved.

  10. Relative bioavailability of a newly developed 5-mg levomethadone hydrochloride IR tablet (L-Polamidon® 5 mg tablets) in comparison with the 5-mg levomethadone hydrochloride oral solution (L-Polamidon® solution for substitution) as reference product.

    Science.gov (United States)

    Blume, Henning H; Wedemeyer, Ralf-Steven; Donath, Frank; Roscher, Katrin; Elvert, Gerd; Wagner, Daniel; Bley, Oliver; Vuia, Alexander; Todorova-Sanjari, Marina; Villalobos, Ramon; Schug, Barbara

    2015-04-01

    To establish the relative bioavailability (rBA) between two p.o. 5-mg levomethadone hydrochloride formulations, i.e., L-Polamidon® 5 mg tablets (test) vs. L-Polamidon® solution for substitution (reference). To assess the safety and tolerability of both formulations. A total of 33 healthy male subjects, aged 29 ± 6 years (BMI: 23.9 ± 2.5 kg/m2) completed this single center, open-label, randomized, 2-period cross-over study with single dose administrations under fasting conditions and coadministration with naltrexone for safety reasons. Administrations of both investigational products were separated by a washout period of at least 2 weeks, i.e., 13 treatmentfree days. The total dose for each subject was 2 x 5 mg resulting in 10 mg levomethadone hydrochloride. For pharmacokinetic evaluation, blood samples were withdrawn until 72 hours postdose. A validated non-stereoselective liquid chromatography-tandem mass spectroscopy method (LC-MS/MS) was applied for the determination of levomethadone in plasma. The lower limit of quantitation was 0.100 ng/mL. Adverse events were descriptively analyzed in the study population. The geometric means of the parameters related with the extent of total exposure of levomethadone, i.e., AUC(0-tlast) and AUC(0-∞), were 244.422 ng x h/mL and 332.999 ng x h/mL for test and 246.837 ng x h/mL and 329.467 ng×h/mL for reference, respectively. The geometric means of the peak exposure for levomethadone, i.e., Cmax, were 8.923 ng/mL for test and 8.635 ng/mL for reference. The point estimates (PEs) of the Test/Reference (T/R) adjusted geometric mean ratios of AUC(0-last), AUC(0-∞), and C(max) were 99.20%, 101.42%, and 104.11%, respectively, and all of them showed 90%-confidence intervals (CIs) within the range of 80.00 - 125.00% as suggested by regulatory requirements for bioequivalence assessment In total, 21 subjects experienced 55 AEs during the study, the most frequently reported AE, i.e., headache, accounted for 13 out of the total

  11. Bilateral femoral head avascular necrosis with a very low dose of oral corticosteroid used for panhypopituitarism.

    Science.gov (United States)

    Dharmshaktu, Pramila; Aggarwal, Anshita; Dutta, Deep; Kulshreshtha, Bindu

    2016-01-13

    Avascular necrosis (AVN) of the femoral head is a rare complication related to glucocorticoid administration and traditionally has been associated with high doses and/or prolonged therapy. Occurrence of osteonecrosis with a physiological replacement dose of glucocorticoids has not been reported previously. We report a 38-year-old man with non-secreting pituitary adenoma who developed bilateral AVN while on a very small dose of oral prednisolone for secondary adrenal insufficiency after surgery for pituitary adenoma. The patient was switched to hydrocortisone. Zolindronic acid was administered and the patient underwent bilateral core decompressive surgery resulting in a reduction of hip pain and improvement. When last evaluated, 2 years after diagnosis of AVN, the patient was functionally independent, and was able to do his routine activities with mild pain. The report intends to highlight the occurrence of AVN of the femur even with a very small dose of prednisolone used for treatment of panhypopituitarism. Glucocorticoids may have to be continued in the lowest possible dose using the most physiological preparation such as hydrocortisone when stoppage is not possible. 2016 BMJ Publishing Group Ltd.

  12. Bilateral femoral head avascular necrosis with a very low dose of oral corticosteroid used for panhypopituitarism

    Science.gov (United States)

    Dharmshaktu, Pramila; Aggarwal, Anshita; Dutta, Deep; Kulshreshtha, Bindu

    2016-01-01

    Avascular necrosis (AVN) of the femoral head is a rare complication related to glucocorticoid administration and traditionally has been associated with high doses and/or prolonged therapy. Occurrence of osteonecrosis with a physiological replacement dose of glucocorticoids has not been reported previously. We report a 38-year-old man with non-secreting pituitary adenoma who developed bilateral AVN while on a very small dose of oral prednisolone for secondary adrenal insufficiency after surgery for pituitary adenoma. The patient was switched to hydrocortisone. Zolindronic acid was administered and the patient underwent bilateral core decompressive surgery resulting in a reduction of hip pain and improvement. When last evaluated, 2 years after diagnosis of AVN, the patient was functionally independent, and was able to do his routine activities with mild pain. The report intends to highlight the occurrence of AVN of the femur even with a very small dose of prednisolone used for treatment of panhypopituitarism. Glucocorticoids may have to be continued in the lowest possible dose using the most physiological preparation such as hydrocortisone when stoppage is not possible. PMID:26762348

  13. Toxicity of the styrene metabolite, phenylglyoxylic acid, in rats after three months' oral dosing

    DEFF Research Database (Denmark)

    Ladefoged, Ole; Lam, Henrik Rye; Ostergaard, G.

    1998-01-01

    Male Wistar rats were dosed with 0, 1250, 3750 or 5000 mg/l of phenylglyoxylic acid (PGA) (CAS no. 611-73-4) in the drinking water ad libitum for 3 months. During the entire treatment period, there were no gross signs of toxicity related to PGA. No changes in neurobehavior were found after using ....... Alternatively, the ototoxicity of styrene, like toluene, may be caused the parent compound itself and not by a metabolite like PGA. (C) 1998 Inter Press, inc....

  14. Peripheral arterial disease in a female using high-dose combined oral contraceptive pills.

    Science.gov (United States)

    Pallavee, P; Samal, Sunita; Samal, Rupal

    2013-01-01

    The association between oral contraceptive (OC) pills and vascular diseases is well-known, although, the present generation of pills is considered to be relatively safer in this regard. Hormonal treatment for severe abnormal uterine bleeding is usually considered after ruling out malignancy, when such bleeding is resistant to all other forms of treatment. We report a case of severe peripheral arterial disease in a female, who had been on high-dose OC pills for an extended period of time for severe uterine bleeding.

  15. Safety and pharmacokinetic profile of fixed-dose ivermectin with an innovative 18mg tablet in healthy adult volunteers.

    Directory of Open Access Journals (Sweden)

    Jose Muñoz

    2018-01-01

    Full Text Available Ivermectin is a pivotal drug for the control of onchocerciasis and lymphatic filariasis, which is increasingly identified as a useful drug for the control of other Neglected Tropical Diseases. Its role in the treatment of soil transmitted helminthiasis through improved efficacy against Trichuris trichiura in combination with other anthelmintics might accelerate the progress towards breaking transmission. Ivermectin is a derivative of Avermectin B1, and consists of an 80:20 mixture of the equipotent homologous 22,23 dehydro B1a and B1b. Pharmacokinetic characteristics and safety profile of ivermectin allow to explore innovative uses to further expand its utilization through mass drug administration campaigns to improve coverage rates. We conducted a phase I clinical trial with 54 healthy adult volunteers who sequentially received 2 experimental treatments using a new 18 mg ivermectin tablet in a fixed-dose strategy of 18 and 36 mg single dose regimens, compared to the standard, weight based 150–200 μg/kg, regimen. Volunteers were recruited in 3 groups based on body weight. Plasma concentrations of ivermectin were measured through HPLC up to 168 hours post treatment. Safety data showed no significant differences between groups and no serious adverse events: headache was the most frequent adverse event in all treatment groups, none of them severe. Pharmacokinetic parameters showed a half-life between 81 and 91 h in the different treatment groups. When comparing the systemic bioavailability (AUC0t and Cmax of the reference product (WA-ref with the other two study groups using fixed doses, we observed an overall increase in AUC0t and Cmax for the two experimental treatments of 18 mg and 36 mg. Body mass index (BMI and weight were associated with t1/2 and V/F, probably reflecting the high liposolubility of IVM with longer retention times proportional to the presence of more adipose tissue. Systemic exposure to ivermectin (AUC0t or Cmax was not

  16. Control de la calidad y estudio de estabilidad del paracetamol gotas orales 100 mg/ml Quality control and stability study of 100 mg/ml paracetamol oral drops

    Directory of Open Access Journals (Sweden)

    Caridad M García Peña

    2013-03-01

    Full Text Available Introducción: las gotas orales de Paracetamol, están indicadas a la población infantil hasta los 5 años para el alivio de la fiebre, dolor de cabeza, dolores dentales y proporciona alivio sintomático del resfriado común. Objetivo: validar dos métodos analíticos, para el control de la calidad y el estudio de estabilidad y estudiar la estabilidad de las gotas orales de producción nacional. Métodos: para cuantificar el principio activo para el estudio de estabilidad, la separación se realizó a través de una columna cromatográfica Lichrosorb RP - 18 (5µm (250 x 4 mm, con detección ultravioleta a 243 nm, empleando una fase móvil compuesta por Agua destilada: Metanol (3:1. Mientras que el método para el control de la calidad se utilizó un Espectrofotómetro SPECTRONIC GENESYS 2.Para el estudio de estabilidad, se emplearon los métodos de vida de estante (a temperatura inferior a 30 º C y de estabilidad acelerada (40 ± 2ºC mediante cromatografía líquida de alta eficiencia. Resultados: los resultados obtenidos de los parámetros evaluados en las validaciones se encontraron dentro de los límites establecidos. Los resultados del estudio de estabilidad realizado, demuestran que el producto terminado cumplió con las especificaciones de calidad durante el estudio. Conclusiones: los métodos analíticos por espectrofotometría UV y cromatografía líquida de alta resolución, son válidos para el control de la calidad y estudio de estabilidad de las gotas orales de Paracetamol 100 mg/mL, ya que resultaron lineales, precisos, exactos y específicos. Se demostró la estabilidad física, química y microbiológica del producto por espacio de 12 meses a temperatura inferior a 30 ºC, envasados en frascos de vidrio ámbar por 15 mL, boca 18 mm, calidad hidrolítica III. Además se evidenció que el producto es estable durante 30 días después de abierto el frasco.Introduction: paracetamol is an effective analgesic and antipyretic drug of

  17. Population pharmacokinetics of artesunate and dihydroartemisinin following single- and multiple-dosing of oral artesunate in healthy subjects

    Directory of Open Access Journals (Sweden)

    Kirsch Lee E

    2009-12-01

    Full Text Available Abstract Background The population pharmacokinetics of artesunate (AS and its active metabolite dihydroartemisinin (DHA were studied in healthy subjects receiving single- or multiple-dosing of AS orally either in combination with pyronaridine (PYR or as a monotherapy with or without food. Methods Data from 118 concentration-time profiles arising from 91 healthy Korean subjects were pooled from four Phase I clinical studies. Subjects received 2-5 mg/kg of single- and multiple-dosing of oral AS either in combination with PYR or as a monotherapy with or without food. Plasma AS and DHA were measured simultaneously using a validated liquid chromatography- mass spectrometric method with a lower limit of quantification of 1 ng/mL for both AS and DHA. Nonlinear mixed-effect modelling was used to obtain the pharmacokinetic and variability (inter-individual and residual variability parameter estimates. Results A novel parent-metabolite pharmacokinetic model consisting of a dosing compartment, a central compartment for AS, a central compartment and a peripheral compartment for DHA was developed. AS and DHA data were modelled simultaneously assuming stoichiometric conversion to DHA. AS was rapidly absorbed with a population estimate of absorption rate constant (Ka of 3.85 h-1. The population estimates of apparent clearance (CL/F and volume of distribution (V2/F for AS were 1190 L/h with 36.2% inter-individual variability (IIV and 1210 L with 57.4% IIV, respectively. For DHA, the population estimates of apparent clearance (CLM/F and central volume of distribution (V3/F were 93.7 L/h with 28% IIV and 97.1 L with 30% IIV, respectively. The population estimates of apparent inter-compartmental clearance (Q/F and peripheral volume of distribution (V4/F for DHA were 5.74 L/h and 18.5 L, respectively. Intake of high-fat and high-caloric meal prior to the drug administration resulted in 84% reduction in Ka. Body weight impacted CLM/F, such that a unit change in

  18. Oral sodium phenylbutyrate in patients with recurrent malignant gliomas: a dose escalation and pharmacologic study.

    Science.gov (United States)

    Phuphanich, Surasak; Baker, Sharyn D; Grossman, Stuart A; Carson, Kathryn A; Gilbert, Mark R; Fisher, Joy D; Carducci, Michael A

    2005-04-01

    We determined the maximum tolerated dose (MTD), toxicity profile, pharmacokinetic parameters, and preliminary efficacy data of oral sodium phenylbutyrate (PB) in patients with recurrent malignant gliomas. Twenty-three patients with supratentorial recurrent malignant gliomas were enrolled on this dose escalation trial. Four dose levels of PB were studied: 9, 18, 27, and 36 g/day. Data were collected to assess toxicity, response, survival, and pharmacokinetics. All PB doses of 9, 18, and 27 g/day were well tolerated. At 36 g/day, two of four patients developed dose-limiting grade 3 fatigue and somnolence. At the MTD of 27 g/day, one of seven patients developed reversible grade 3 somnolence. Median survival from time of study entry was 5.4 months. One patient had a complete response for five years, and no partial responses were noted, which yielded an overall response rate of 5%. Plasma concentrations of 706, 818, 1225, and 1605 muM were achieved with doses of 9, 18, 27, and 36 g/day, respectively. The mean value for PB clearance in this patient population was 22 liters/h, which is significantly higher than the 16 liters/h reported in patients with other malignancies who were not receiving P450 enzyme-inducing anticonvulsant drugs (P = 0.038). This study defines the MTD and recommended phase 2 dose of PB at 27 g/day for heavily pretreated patients with recurrent gliomas. The pharmacology of PB appears to be affected by concomitant administration of P450-inducing anticonvulsants.

  19. Oral sodium phenylbutyrate in patients with recurrent malignant gliomas: A dose escalation and pharmacologic study1

    Science.gov (United States)

    Phuphanich, Surasak; Baker, Sharyn D.; Grossman, Stuart A.; Carson, Kathryn A.; Gilbert, Mark R.; Fisher, Joy D.; Carducci, Michael A.

    2005-01-01

    We determined the maximum tolerated dose (MTD), toxicity profile, pharmacokinetic parameters, and preliminary efficacy data of oral sodium phenylbutyrate (PB) in patients with recurrent malignant gliomas. Twenty-three patients with supratentorial recurrent malignant gliomas were enrolled on this dose escalation trial. Four dose levels of PB were studied: 9, 18, 27, and 36 g/day. Data were collected to assess toxicity, response, survival, and pharmacokinetics. All PB doses of 9, 18, and 27 g/day were well tolerated. At 36 g/day, two of four patients developed dose-limiting grade 3 fatigue and somnolence. At the MTD of 27 g/day, one of seven patients developed reversible grade 3 somnolence. Median survival from time of study entry was 5.4 months. One patient had a complete response for five years, and no partial responses were noted, which yielded an overall response rate of 5%. Plasma concentrations of 706, 818, 1225, and 1605 μM were achieved with doses of 9, 18, 27, and 36 g/day, respectively. The mean value for PB clearance in this patient population was 22 liters/h, which is significantly higher than the 16 liters/h reported in patients with other malignancies who were not receiving P450 enzyme–inducing anticonvulsant drugs (P = 0.038). This study defines the MTD and recommended phase 2 dose of PB at 27 g/day for heavily pretreated patients with recurrent gliomas. The pharmacology of PB appears to be affected by concomitant administration of P450-inducing anticonvulsants. PMID:15831235

  20. Efficacy, safety and tolerability of escitalopram in doses up to 50 mg in Major Depressive Disorder (MDD: an open-label, pilot study

    Directory of Open Access Journals (Sweden)

    Crawford Gordon M

    2011-03-01

    Full Text Available Abstract Background Escitalopram is licensed for use at doses up to 20 mg but is used clinically at higher doses. There is limited published data at higher doses and none in the treatment of Major Depressive Disorder (MDD. Methods This open-label, pilot study was designed to investigate the efficacy, safety and tolerability of escitalopram in doses up to 50 mg in MDD. It was conducted in 60 primary care patients with MDD who had not responded to adequate treatment with citalopram. Patients were treated with escalating doses of escitalopram up to 50 mg for up to 32 weeks until they achieved remission (Montgomery-Asberg Depression Rating Scale [MADRS] ≤8 or failed to tolerate the dose. Results Forty-two patients (70% completed the study. Twenty-one patients (35% achieved remission with 8 of the 21 patients (38% needing the 50 mg dose to achieve remission. Median time to remission was 24 weeks and median dose in remission was 30 mg. No significant safety issues were identified although tolerability appeared to decline above a dose of 40 mg with 26% of patients unable to tolerate 50 mg. Twelve (20% patients had adverse events leading to discontinuation. The most common adverse events were headache (35%, nausea, diarrhoea and nasopharyngitis (all 25%. Minor mean weight gain was found during the study, which did not appear to be dose-related. Half of the patients who completed the study chose to continue treatment with escitalopram rather than taper down the dose at 32 weeks. Conclusions Dose escalation with escitalopram above 20 mg may have a useful role in the management of patients with MDD, although further studies are needed to confirm this finding. Trial Registration ClinicalTrials.gov: NCT00785434

  1. Regulation of operant oral ethanol self-administration: a dose-response curve study in rats.

    Science.gov (United States)

    Carnicella, Sebastien; Yowell, Quinn V; Ron, Dorit

    2011-01-01

    Oral ethanol self-administration procedures in rats are useful preclinical tools for the evaluation of potential new pharmacotherapies as well as for the investigation into the etiology of alcohol abuse disorders and addiction. Determination of the effects of a potential treatment on a full ethanol dose-response curve should be essential to predict its clinical efficacy. Unfortunately, this approach has not been fully explored because of the aversive taste reaction to moderate to high doses of ethanol, which may interfere with consumption. In this study, we set out to determine whether a meaningful dose-response curve for oral ethanol self-administration can be obtained in rats. Long-Evans rats were trained to self-administer a 20% ethanol solution in an operant procedure following a history of excessive voluntary ethanol intake. After stabilization of ethanol self-administration, the concentration of the solution was varied from 2.5 to 60% (v/v), and operant and drinking behaviors, as well as blood ethanol concentration (BEC), were evaluated following the self-administration of a 20, 40, and 60% ethanol solution. Varying the concentration of ethanol from 2.5 to 60% after the development of excessive ethanol consumption led to a typical inverted U-shaped dose-response curve. Importantly, rats adapted their level and pattern of responding to changes in ethanol concentration to obtain a constant level of intake and BEC, suggesting that their operant behavior is mainly driven by the motivation to obtain a specific pharmacological effect of ethanol. This procedure can be a useful and straightforward tool for the evaluation of the effects of new potential pharmacotherapies for the treatment of alcohol abuse disorders. Copyright © 2010 by the Research Society on Alcoholism.

  2. Effect of Admission Oral Diuretic Dose on Response to Continuous versus Bolus Intravenous Diuretics in Acute Heart Failure: An Analysis from DOSE-AHF

    Science.gov (United States)

    Shah, Ravi V.; McNulty, Steven; O'Connor, Christopher M.; Felker, G. Michael; Braunwald, Eugene; Givertz, Michael M.

    2014-01-01

    Background Results from the Diuretic Optimization Strategies in Acute Heart Failure (DOSE-AHF) study suggest that an initial continuous infusion of loop diuretics is not superior to bolus dosing with regard to clinical endpoints in AHF. We hypothesized that outpatient furosemide dose was associated with congestion and poorer renal function, and explored the hypothesis that a continuous infusion may be more effective in patients on higher outpatient diuretic doses. Methods DOSE-AHF randomized 308 patients within 24 hours of admission to high vs. low initial intravenous diuretic dose given as either a continuous infusion or bolus. We compared baseline characteristics and assessed associations between mode of administration (bolus vs. continuous) and outcomes in patients receiving high-dose (≥120 mg furosemide equivalent, n=177) versus low-dose (diuretics. Results Patients on higher doses of furosemide were less frequently on renin-angiotensin system inhibitors (P=.01), and had worse renal function and more advanced symptoms. There was a significant interaction between outpatient dose and mode of therapy (P=0.01) with respect to net fluid loss at 72 hours after adjusting for creatinine and intensification strategy. Admission diuretic dose was associated with an increased risk of death or rehospitalization at 60 days (adjusted HR=1.08 per 20-mg increment in dose, 95% CI 1.01–1.16, P=.03). Conclusions In acute HF, patients on higher diuretic doses have greater disease severity, and may benefit from an initial bolus strategy. PMID:23194486

  3. Mass balance, metabolic disposition, and pharmacokinetics of a single oral dose of regorafenib in healthy human subjects.

    Science.gov (United States)

    Gerisch, Michael; Hafner, Frank-Thorsten; Lang, Dieter; Radtke, Martin; Diefenbach, Konstanze; Cleton, Adriaan; Lettieri, John

    2018-01-01

    To evaluate the mass balance, metabolic disposition, and pharmacokinetics of a single dose of regorafenib in healthy volunteers. In addition, in vitro metabolism of regorafenib in human hepatocytes was investigated. Four healthy male subjects received one 120 mg oral dose of regorafenib containing approximately 100 µCi (3.7 MBq) [ 14 C]regorafenib. Plasma concentrations of parent drug were derived from HPLC-MS/MS analysis and total radioactivity from liquid scintillation counting (LSC). Radiocarbon analyses used HPLC with fraction collection followed by LSC for all urine samples, plasma, and fecal homogenate extracts. For the in vitro study, [ 14 C]regorafenib was incubated with human hepatocytes and analyzed using HPLC-LSC and HPLC-HRMS/MS. Regorafenib was the major component in plasma, while metabolite M-2 (pyridine N-oxide) was the most prominent metabolite. Metabolites M-5 (demethylated pyridine N-oxide) and M-7 (N-glucuronide) were identified as minor plasma components. The mean concentration of total radioactivity in plasma/whole blood appeared to plateau at 1-4 h and again at 6-24 h post-dose. In total, 90.5% of administered radioactivity was recovered in the excreta within a collection interval of 12 days, most of which (71.2%) was eliminated in feces, while excretion via urine accounted for 19.3%. Regorafenib (47.2%) was the most prominent component in feces and was not excreted into urine. Excreted metabolites resulted from oxidative metabolism and glucuronidation. Regorafenib was eliminated predominantly in feces as well as by hepatic biotransformation. The multiple biotransformation pathways of regorafenib decrease the risk of pharmacokinetic drug-drug interactions.

  4. Use of low-dose oral theophylline as an adjunct to inhaled corticosteroids in preventing exacerbations of chronic obstructive pulmonary disease: study protocol for a randomised controlled trial.

    Science.gov (United States)

    Devereux, Graham; Cotton, Seonaidh; Barnes, Peter; Briggs, Andrew; Burns, Graham; Chaudhuri, Rekha; Chrystyn, Henry; Davies, Lisa; De Soyza, Anthony; Fielding, Shona; Gompertz, Simon; Haughney, John; Lee, Amanda J; McCormack, Kirsty; McPherson, Gladys; Morice, Alyn; Norrie, John; Sullivan, Anita; Wilson, Andrew; Price, David

    2015-06-10

    Chronic obstructive pulmonary disease (COPD) is associated with high morbidity, mortality, and health-care costs. An incomplete response to the anti-inflammatory effects of inhaled corticosteroids is present in COPD. Preclinical work indicates that 'low dose' theophylline improves steroid responsiveness. The Theophylline With Inhaled Corticosteroids (TWICS) trial investigates whether the addition of 'low dose' theophylline to inhaled corticosteroids has clinical and cost-effective benefits in COPD. TWICS is a randomised double-blind placebo-controlled trial conducted in primary and secondary care sites in the UK. The inclusion criteria are the following: an established predominant respiratory diagnosis of COPD (post-bronchodilator forced expiratory volume in first second/forced vital capacity [FEV1/FVC] of less than 0.7), age of at least 40 years, smoking history of at least 10 pack-years, current inhaled corticosteroid use, and history of at least two exacerbations requiring treatment with antibiotics or oral corticosteroids in the previous year. A computerised randomisation system will stratify 1424 participants by region and recruitment setting (primary and secondary) and then randomly assign with equal probability to intervention or control arms. Participants will receive either 'low dose' theophylline (Uniphyllin MR 200 mg tablets) or placebo for 52 weeks. Dosing is based on pharmacokinetic modelling to achieve a steady-state serum theophylline of 1-5 mg/l. A dose of theophylline MR 200 mg once daily (or placebo once daily) will be taken by participants who do not smoke or participants who smoke but have an ideal body weight (IBW) of not more than 60 kg. A dose of theophylline MR 200 mg twice daily (or placebo twice daily) will be taken by participants who smoke and have an IBW of more than 60 kg. Participants will be reviewed at recruitment and after 6 and 12 months. The primary outcome is the total number of participant-reported COPD exacerbations requiring

  5. Prophylactic single-dose administration of 600 mg clindamycin versus 4-time administration of 600 mg clindamycin in orthognathic surgery: A prospective randomized study in bilateral mandibular sagittal ramus osteotomies

    NARCIS (Netherlands)

    Lindeboom, Jerôme A. H.; Baas, Eric M.; Kroon, Frans H. M.

    2003-01-01

    Objective. The purpose of this study was to compare a single 600-mg dose of preoperative intravenously administered clindamycin with a 24-hour 600-mg regimen of clindamycin as prophylaxis for postoperative infections in bilateral sagittal ramus osteotomies. Study design. Seventy patients were

  6. Successful comeback of the single-dose live oral cholera vaccine CVD 103-HgR.

    Science.gov (United States)

    Herzog, Christian

    2016-01-01

    Effective and easy to administer cholera vaccines are in need more than ever, for at risk populations and travellers alike. In many parts of the world cholera is still endemic, causing outbreaks and constituting repeatedly serious public health problems. The oral live cholera vaccine CVD 103-HgR (Orochol, Mutachol), the first genetically modified organism (GMO) used as vaccine, was in its time (launched 1993, Switzerland) the ideal cholera vaccine: single-dose, protective efficacy of 80-100% against moderate to severe cholera, acting within 8 days and exhibiting excellent safety, indiscernible from placebo. However, there were strong headwinds: In the 1990s the indication for cholera vaccines was generally downplayed by experts and in 1997 the European Commission called for a moratorium of GMOs which blocked the registration in the European Union. Thus, demand for this vaccine remained low and in 2003 it was taken off the market for economic reasons. After a decade in obscurity it (Vaxchora) has resurfaced again, now produced in the U.S. and equipped with a U.S. FDA license (June 10, 2016). What had happened? This commentary gives a critical account of an almost unbelievable string of misadventures, emerging adverse circumstances and man-made failures which nearly killed this single-dose live oral cholera vaccine. The good news is that patience and persistence lead to success in the end, allowing good science to prevail for the benefit of those in need. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Phase I trial of split-dose induction docetaxel, cisplatin, and 5-fluorouracil (TPF chemotherapy followed by curative surgery combined with postoperative radiotherapy in patients with locally advanced oral and oropharyngeal squamous cell cancer (TISOC-1

    Directory of Open Access Journals (Sweden)

    Oertel Katrin

    2012-10-01

    Full Text Available Abstract Background Induction chemotherapy (ICT with docetaxel, cisplatin and fluorouracil (TPF followed by radiotherapy is an effective treatment option for unresectable locally advanced head and neck cancer. This phase I study was designed to investigate the safety and tolerability of a split-dose TPF ICT regimen prior to surgery for locally advanced resectable oral and oropharyngeal cancer. Methods Patients received TPF split on two dosages on day 1 and 8 per cycle for one or three 3-week cycles prior to surgery and postoperative radiotherapy or radiochemotherapy. Docetaxel was escalated in two dose levels, 40 mg/m2 (DL 0 and 30 mg/m2 (DL −1, plus 40 mg/m2 cisplatin and 2000 mg/m2 fluorouracil per week using a 3 +3 dose escalation algorithm. Results Eighteen patients were enrolled and were eligible for toxicity and response. A maximum tolerated dose of 30 mg/m2 docetaxel per week was reached. The most common grade 3+ adverse event was neutropenia during ICT in 10 patients. Surgery reached R0 resection in all cases. Nine patients (50% showed complete pathologic regression. Conclusions A split-dose regime of TPF prior to surgery is feasible, tolerated and merits additional investigation in a phase II study with a dose of 30 mg/m docetaxel per week. Trial registration number NCT01108042 (ClinicalTrials.gov Identifier

  8. A 14-day repeated-dose oral toxicological evaluation of an isothiocyanate-enriched hydro-alcoholic extract from Moringa oleifera Lam. seeds in rats.

    Science.gov (United States)

    Kim, Youjin; Jaja-Chimedza, Asha; Merrill, Daniel; Mendes, Odete; Raskin, Ilya

    2018-01-01

    A 14-d short-term oral toxicity study in rats evaluated the safety of moringa isothiocyanate-1 (MIC-1)-enriched hydro-alcoholic moringa seeds extract (MSE). Rats (5 males/5 females per group) were gavaged daily for 14 d with the vehicle control or MSE, at 78 (low), 257 (mid-low), 772 (mid-high), or 2571 (high) mg/kg bw/d, standardized to MIC-1 (30, 100, 300, or 1000 mg/kg bw/d, respectively). Toxicological endpoints included body weight and weight gain, food consumption and feed efficiency, clinical observations, hematology, gross necropsy and histopathology, and relative organ weights. Mortality was only observed in the high dose group animals, both male and female, representing decreases in body weight/weight gain and food consumption/feed efficiency. Irregular respiratory patterns and piloerection were major clinical observations found primarily in the mid-high and high dose group animals. In the high dose group, gastrointestinal distention and stomach discoloration were observed in non-surviving males and females, and degeneration and necrosis of the testicular germinal cells and epididymal cells were also observed in a non-surviving male. Increased liver weights were found in females in the mid-high and high dose groups. Animals in the low and mid-low groups did not exhibit adverse effects of MSE (100 mg/kg bw/d MIC-1). A no observed adverse effect level (NOAEL) of the standardized MSE was determined as 257 mg/kg bw/d providing 100 mg/kg bw/d MIC-1.

  9. The Lack of Effect of Food on the Pharmacokinetics of ZX008 (Fenfluramine Oral Solution): Results of a Single-dose, Two-period Crossover Study.

    Science.gov (United States)

    Gammaitoni, Arnold; Smith, Steven; Boyd, Brooks

    2018-06-22

    Fenfluramine is being developed as a low-dose adjunctive treatment for seizures in patients with Dravet syndrome and other epileptic encephalopathies, including Lennox-Gastaut syndrome. Most patients with Dravet syndrome receive multiple antiepileptic drugs, making it challenging for caregivers to track correct administration times. The present Phase I study was conducted to determine the effect of food on the pharmacokinetic properties of fenfluramine. Healthy nonsmoking subjects aged 18 to 50years were enrolled in an open-label, crossover, Phase I pharmacokinetic and safety profile study and received 2 single 0.8-mg/kg doses of ZX008 (fenfluramine hydrochloride oral solution), 1 after a 10-hour overnight fast and the other 30 minutes after the start of consumption of a high-fat breakfast, in a randomly assigned order. A washout period of at least 9days separated the 2 treatment periods. Venous blood samples were taken before each dose and periodically for 72hours after each dose for determination of concentrations of fenfluramine and its active metabolite norfenfluramine. Plasma pharmacokinetic parameters were estimated for each subject by noncompartmental analysis. In the 13 subjects completing both treatment periods, food had no effect on the rate or extent of absorption and bioavailability of fenfluramine as assessed by fed vs fasted adjusted geometric mean observed plasma C max (59.1vs 56.7 ng/mL; NS) and AUC 0-∞ (1640vs 1600 ng · h/mL; NS). Additionally, there was no impact of food on systemic exposure of norfenfluramine. Seven subjects reported at least 1 treatment-emergent adverse event; all treatment-emergent adverse events were mild in severity. The bioequivalence and tolerability of single 0.8-mg/kg oral doses of ZX008 in the fed and fasted states support ZX008 administration without regard to meals. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  10. Measurement of low-LET radiation dose aboard the chinese scientific experiment satellite (1988) by highly sensitive LiF (Mg, Cu, P) TL chips

    International Nuclear Information System (INIS)

    Zhang Zhonglun; Zheng Yanzhen.

    1989-01-01

    Low-LET radiation dose is an important portion of spaceflight dose. It is a new application that highly sensitive LiF(Mg, Cu, P) TL chips are used in measurement of low-LET dose aboard the chinese scientific experiment satellite. Avarage dose rate in satellite is 9.2 mrad/day and on the ground is about 0.32 mrad/day

  11. Evaluation of an ultra-low-dose oral contraceptive for dysmenorrhea: a placebo-controlled, double-blind, randomized trial.

    Science.gov (United States)

    Harada, Tasuku; Momoeda, Mikio

    2016-12-01

    To evaluate the efficacy and safety of an ultra-low-dose oral contraceptive (NPC-01; 0.02 mg ethinyl estradiol and 1 mg norethisterone) in subjects with dysmenorrhea. Placebo-controlled, double-blind, randomized trial. Clinical trial sites. Two hundred fifteen subjects with dysmenorrhea. Subjects were randomly assigned to receive NPC-01, placebo, or IKH-01 (0.035 mg ethinyl estradiol and 1 mg norethisterone) for four cycles. Total dysmenorrhea score (verbal rating scale) assessing pain on the basis of limited ability to work and need for analgesics. The reductions of total dysmenorrhea score and visual analog scale score after the treatment were significantly higher in the NPC-01 group than in the placebo group. Furthermore, the efficacy of NPC-01 was comparable to that of IKH-01. The overall incidence of side effects was significantly higher in the NPC-01 group than in the placebo group. All side effects that occurred in the NPC-01 group were previously reported in patients receiving IKH-01. No serious side effects occurred. The ultra-low-dose contraceptive NPC-01 relieved dysmenorrhea as effectively as IKH-01. Thus, NPC-01 could represent a new option for long-term treatment of dysmenorrhea. NCT01129102. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  12. The impact of a 600-mg loading dose of clopidogrel in diabetic and non-diabetic patients undergoing elective PCI.

    Science.gov (United States)

    Mohareb, Mina W; Abd Elghany, Mohamed; Sabry, Nirmeen A; Farid, Samar F

    2016-08-01

    High platelet reactivity (HPR) and suboptimal response to dual antiplatelet therapy (DAPT) may explain high recurrent rates of ischemic events in type 1 and 2 diabetes mellitus (DM) patients undergoing percutaneous coronary intervention (PCI). The aim of this study was to determine the effect of diabetes mellitus on clopidogrel activity in cardiac patients undergoing PCI. This is an observational study. Patients were categorized according to DM status into diabetic group (N.=30) and non-diabetic group (N.=33). All patients received clopidogrel in a loading dose of 600 mg before PCI. Platelet function was assessed using light transmittance aggregometry (LTA) technique at baseline (before clopidogrel administration), 24 hour after clopidogrel loading dose administration and 7-10 days after PCI. All patients were followed up for at least one year after PCI for recurrence of acute cardiac events. There was no statistically significant difference between the two groups with respect to 10 µm adenosine diphosphate (ADP)-induced platelet aggregation measured at baseline (P=0.64), 24 hours after PCI (P=0.874), and 7-10 days after PCI (0.643). Diabetics were not significantly different from non-diabetics in terms of post-PCI acute stent thrombosis (P=0.945), sub-acute stent thrombosis (P=0.945), unstable angina (P=0.29) and cardiac death (P=0.64). There was a statistically significant difference between patients with and without post-PCI acute events regarding ADP aggregation measured 24 hours and 7-10 days after PCI. The use of a high loading dose of clopidogrel (600 mg) in patients undergoing elective PCI can overcome the significant increase in post-PCI platelet aggregation and rate of acute cardiac events induced by diabetes mellitus as co-morbidity in those patients.

  13. Monte Carlo method for dose calculation due to oral X-rays

    International Nuclear Information System (INIS)

    Loureiro, Eduardo Cesar de Miranda

    1998-06-01

    The increasing utilization of oral X-rays, especially in youngsters and children, calls for the assessment of equivalent doses in their organs and tissues. With this purpose, a Monte Carlo code was adapted to simulate an X-ray source irradiating phantoms of the MIRD-5 type with different ages (10, 15 and 40 years old) to calculate the conversion coefficients which transform the exposure at skin to equivalent doses at several organs and tissues of interest. In order to check the computer program, simulations were performed for adult patients using the original code (ADAM.FOR developed at the GSF-Germany) and the adapted program (MCDRO.PAS). Good agreement between results obtained with both codes was observed. Irradiations of the incisive, canine and molar teeth were simulated. The conversion factors were calculated for the following organs and tissues: thyroid, active bone narrow (head and whole body), bone (facial skeleton, cranium and whole body), skin (head and whole body) and crystalline. Based on the obtained results, it follows that the younger the patient and the larger the field area, the higher the dose in assessed organs and tissues. The variation of the source-skin distance does not change the conversion coefficients. On the other hand, the increase in the voltage applied to the X-ray tube causes an increase in the calculated conversion coefficients. (author)

  14. Effect of Oral Administration of “Gadagi” Tea on Lipid Profile in Rats ...

    African Journals Online (AJOL)

    Abstract: Effect of oral administration of “Gadagi” tea on lipid profile was assessed in 50 healthy male albino rats which were grouped and administered with different doses(mg/kg) i.e low dose (380mg/kg, 415mg/kg, 365mg/kg,. 315mg/kg for “sak”, ”sada” and “magani” respectively), standard dose (760mg/kg, 830mg/kg, ...

  15. Influence of Vehicles Used for Oral Dosing of Test Molecules on the Progression of Mycobacterium tuberculosis Infection in Mice

    OpenAIRE

    Singh, Shubhra; Dwivedi, Richa; Chaturvedi, Vinita

    2014-01-01

    Preclinical evaluation of drug-like molecules requires their oral administration to experimental animals using suitable vehicles. We studied the effect of oral dosing with corn oil, carboxymethyl cellulose, dimethyl sulfoxide, and polysorbate-80 on the progression of Mycobacterium tuberculosis infection in mice. Infection was monitored by physical (survival time and body weight) and bacteriological (viable counts in lungs) parameters. Compared with water, corn oil significantly improved both ...

  16. Pharmacokinetics of single oral dose of pimobendan in Hispaniolan Amazon parrots (Amazona ventralis).

    Science.gov (United States)

    Guzman, David Sanchez-Migallon; Beaufrère, Hugues; KuKanich, Butch; Barker, Steven A; Brandão, João; Paul-Murphy, Joanne; Tully, Thomas N

    2014-06-01

    Pimobendan is a phosphodiesterase (PDE) inhibitor and calcium sensitizer with inotropic, lusitropic, and rasodilator properties used in the treatment of congestive heart failure. The mechanism of action is by inhibition of PDE III and V and by increasing intracellular calcium sensitivity in the cardiac myocardium. Pharmacokinetic and pharmacodynamic studies have been published in humans, dogs, and cats, but there are no studies in avian species. Pimobendan has been used in birds at the empirical dosage of 0.25 mg/kg q12h. To determine the pharmacokinetic parameters of pimobendan in Hispaniolan Amazon parrots (Amazona ventralis), 3 pilot studies with 2 birds, each receiving 1, 3, and 10 mg/kg PO, provided the basis for the pivotal trials with 6 birds, each receiving 10 mg/kg PO using 2 different suspensions. Blood samples were obtained at 0, 0.5, 1, 1.5, 2, 3, 4, 8, 12, and 18 hours after drug administration. Plasma concentrations were determined by liquid chromatography-tandem mass spectrometry (HPLC/MS) by use of electrospray ionization. Because of the erratic and low concentrations of pimobendan, pharmacokinetic parameters were calculated using naive averaged analysis. Plasma concentrations after commercial pimobendan tablet suspension at 10 mg/kg reached a Cmax of 8.26 ng/mL at 3 hours with a terminal half-life of 2.1 hours, while concentrations after the bulk chemical suspension reached a Cmax of 1.28 ng/mL at 12 hours and had a terminal half-life of 2.3 hours. Further studies evaluating the effect of oral pimobendan in parrots are needed.

  17. Low energy helium-neon laser prevents oral mucositis after high-dose chemo-radiotherapy: results of a double-blind randomized trial

    International Nuclear Information System (INIS)

    Cowen, Didier; Tardieu, Corinne; Resbeut, Michel; Hannoun-Levi, Jean-Michel; Alzieu, Claude; Schubert, Marc; Franquin, Jean-Claude

    1996-01-01

    Purpose: To evaluate the efficiency of Helium-Neon (He-Ne) laser in the prevention of oral mucositis (OM) induced by high dose chemoradiotherapy before bone marrow transplantation (BMT). Methods and materials: Between 1993 and 1995, 30 consecutive patients (pts) receiving an autologous peripheral stem-cell or bone marrow transplant (BMT) after high dose chemoradiotherapy were randomized to receive or not prophylactic laser applications to the oral mucosa. Chemotherapy consisted of cyclophosphamide, 60 mg/kg intravenously (IV) on day (d)-5 and d-4 in 27 cases, or melphalan 140 mg/kg IV on d-4 in 3 cases. Total body irradiation consisted of 12 Gy midplane dose in six fractions and 3 days. He-Ne laser (632.8 nm wavelength, power 60 mW) applications were performed daily from d-5 to d-1 on 5 anatomic sites of the oral mucosa. Oral examination was performed daily from d0 to d+20. Mucositis was scored according to an oral exam guide with a 16 items scale of which 4 were assessed by the pts themselves. Mean daily scores of pain, ability to swallow and saliva production were measured. A daily mucositis index (DMI) and a cumulative score of oral mucositis (CSOM) were established. Requirement for narcotics and parenteral nutrition were measured. Validation of the grading scale was carried out using the Cronbach alpha coefficient for the internal validation and the test-retest correlation coefficient for the reproducibility analysis. The U Mann Whitney test was used to test for differences among groups. Patients were assigned to either laser treatment (L+) or sham-treatment (L-) by computer blocked randomization. Results: No pt was excluded for failure to complete the laser application protocol. Laser applications were well tolerated and no side effects were reported. The items were highly interrelated as well as the index considered as a whole: over 21 days, α = 0.97. Reproducibility analysis between the nurses in charge with the oral examination showed a significant

  18. PHARMACOKINETICS OF TRAMADOL HYDROCHLORIDE AND ITS METABOLITE O-DESMETHYLTRAMADOL FOLLOWING A SINGLE, ORALLY ADMINISTERED DOSE IN CALIFORNIA SEA LIONS (ZALOPHUS CALIFORNIANUS).

    Science.gov (United States)

    Boonstra, Jennifer L; Barbosa, Lorraine; Van Bonn, William G; Johnson, Shawn P; Gulland, Frances M D; Cox, Sherry K; Martin-Jimenez, Tomas

    2015-09-01

    Tramadol is a synthetic, centrally acting, opiate-like analgesic that is structurally related to codeine and morphine. The objective of this study was to determine the pharmacokinetics of tramadol hydrochloride and its major active metabolite O-desmethyltramadol (M1) in the California sea lion (Zalophus californianus). A single dose of tramadol was administered orally in fish at 2 mg/kg to a total of 15 wild California sea lions admitted for rehabilitation. Twenty-four total blood samples were collected post drug administration at 10, 20, 30, and 45 min and at 1, 3, 5, 6, 8, 12, and 24 hr. Blood plasma was separated and stored at -80°C until analysis with high-performance liquid chromatography was performed to determine levels of tramadol and M1, the major active metabolite. The results indicate that the plasma levels of parent tramadol are low or negligible during the first 30-45 min and then reach the predicted mean maximum plasma concentration of 358 ng/ml at 1.52 hr. The M1 metabolite was not detectable in 21 of 24 plasma samples, below the level of quantification of 5 ng/ml in one sample, and detectable at 11 and 17 ng/ml in two of the samples. This study suggests that a 2 mg/kg dose would need to be administered every 6-8 hr to maintain concentrations of tramadol above the minimum human analgesic level for mild to moderate pain. Based on dosing simulations, a dose of 4 mg/kg q8 hr or q12 hr, on average, may represent an adequate compromise, but further studies are needed using a larger sample size. Pharmacodynamic studies are warranted to determine if tramadol provides analgesic effects in this species. The potential for tramadol toxicosis at any dose also has not been determined in this species.

  19. Quality of Life of Oral Cancer Patients After Low-Dose-Rate Interstitial Brachytherapy

    International Nuclear Information System (INIS)

    Yoshimura, Ryo-ichi; Shibuya, Hitoshi; Miura, Masahiko; Watanabe, Hiroshi; Ayukawa, Fumio; Hayashi, Keiji; Toda, Kazuma

    2009-01-01

    Purpose: To assess the quality of life (QOL) of oral cancer patients treated with low-dose-rate interstitial brachytherapy (LDR-BT) alone. Methods and Materials: Between June 2005 and July 2006, a total of 56 patients with oral cancer were enrolled in this prospective study. QOL was assessed by means of the core questionnaire and head and neck questionnaire module of the European Organization for Research and Treatment of Cancer (EORTC Quality of Life Questionnaire-Core 30 [QLQ-C30] and QLQ Head and Neck 35 [H and N35]). The questionnaires were distributed to the patients before the start of treatment and 3 months, 6 months, and 12 months after the start of LDR-BT. Results: It was possible to analyze the results for 20 of the initial 56 patients because they did not experience metastasis or recurrence during this study. No functions or symptoms asked about in the QLQ-C30 deteriorated during the first year. The emotional function score steadily and significantly increased. No symptoms in the QLQ-H and N35 significantly deteriorated. The scores for pain, trouble with social eating, and weight loss on the QLQ-H and N35 steadily and significantly decreased. Age, gender, and LDR-BT source had no effect on the change in QOL during the first year, but T-stage significantly affected the change in global health status, tumor site affected the changes in swallowing, sensory problems, sticky saliva, and complications affected the changes in pain, swallowing, and mouth opening. Conclusions: QOL of oral cancer patients treated with LDR-BT is high. However, tumor stage, tumor site, and complications affected the changes in a few functions and symptoms during the first year

  20. In vivo effect of single oral dose of artemether against early juvenile stages of Schistosoma mansoni Egyptian strain.

    Science.gov (United States)

    El-Beshbishi, Samar N; Taman, Amira; El-Malky, Mohamed; Azab, Manar S; El-Hawary, Amira K; El-Tantawy, Dina A

    2013-10-01

    The current treatment and control of schistosomiasis, rely on a single drug, praziquantel, although, it has minor activity against juvenile stages of the parasite. Studies have shown that artemether (ART) exhibits effects against juveniles of Schistosoma mansoni Liberian and Puerto Rican strains, Schistosoma japonicum and Schistosoma haematobium. Aiming to assess the in vivo activity of single oral dose of ART against early juvenile stages of S. mansoni Egyptian strain, this study was established. Mice were treated with ART (400 mg/kg) at two time points evenly spaced over the period of larval development (7 and 21 days post-infection; pi), and a third treatment point (day 49 pi) was included to elucidate when susceptibility decreases. Administration of ART on day 7 pi reduced the total worm burden by 85.94%. The greatest reductions were seen when treatment was given on day 21 pi, with total and female worm burden reductions of 91.52% and 90.57%, respectively, and cessation of oviposition. Similar dose given on day 49 pi reduced total worm burden by 55.17% and female worm burden by 66.51%. Moreover, it induced significant reduction in the tissue egg load and significant alterations in the oogram pattern with decreased immature eggs and increased dead eggs. Antipathological activities were evident in significant reductions in granulomata count and diameter. In conclusion, ART exhibits major in vivo schistosomicidal effects against the early larval migratory stages of S. mansoni Egyptian strain, mainly the 21-day old schistosomula, hence preventing disease progression and morbidity. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Prospective Evaluation to Establish a Dose Response for Clinical Oral Mucositis in Patients Undergoing Head-and-Neck Conformal Radiotherapy

    International Nuclear Information System (INIS)

    Narayan, Samir; Lehmann, Joerg; Coleman, Matthew A.; Vaughan, Andrew; Yang, Claus Chunli; Enepekides, Danny; Farwell, Gregory; Purdy, James A.; Laredo, Grace; Nolan, Kerry A.S.; Pearson, Francesca S.; Vijayakumar, Srinivasan

    2008-01-01

    Purpose: We conducted a clinical study to correlate oral cavity dose with clinical mucositis, perform in vivo dosimetry, and determine the feasibility of obtaining buccal mucosal cell samples in patients undergoing head-and-neck radiation therapy. The main objective is to establish a quantitative dose response for clinical oral mucositis. Methods and Materials: Twelve patients undergoing radiation therapy for head-and-neck cancer were prospectively studied. Four points were chosen in separate quadrants of the oral cavity. Calculated dose distributions were generated by using AcQPlan and Eclipse treatment planning systems. MOSFET dosimeters were used to measure dose at each sampled point. Each patient underwent buccal sampling for future RNA analysis before and after the first radiation treatment at the four selected points. Clinical and functional mucositis were assessed weekly according to National Cancer Institute Common Toxicity Criteria, Version 3. Results: Maximum and average doses for sampled sites ranged from 7.4-62.3 and 3.0-54.3 Gy, respectively. A cumulative point dose of 39.1 Gy resulted in mucositis for 3 weeks or longer. Mild severity (Grade ≤ 1) and short duration (≤1 week) of mucositis were found at cumulative point doses less than 32 Gy. Polymerase chain reaction consistently was able to detect basal levels of two known radiation responsive genes. Conclusions: In our sample, cumulative doses to the oral cavity of less than 32 Gy were associated with minimal acute mucositis. A dose greater than 39 Gy was associated with longer duration of mucositis. Our technique for sampling buccal mucosa yielded sufficient cells for RNA analysis using polymerase chain reaction

  2. Predicting biopharmaceutical performance of oral drug candidates - Extending the volume to dissolve applied dose concept.

    Science.gov (United States)

    Muenster, Uwe; Mueck, Wolfgang; van der Mey, Dorina; Schlemmer, Karl-Heinz; Greschat-Schade, Susanne; Haerter, Michael; Pelzetter, Christian; Pruemper, Christian; Verlage, Joerg; Göller, Andreas H; Ohm, Andreas

    2016-05-01

    The purpose of the study was to experimentally deduce pH-dependent critical volumes to dissolve applied dose (VDAD) that determine whether a drug candidate can be developed as immediate release (IR) tablet containing crystalline API, or if solubilization technology is needed to allow for sufficient oral bioavailability. pH-dependent VDADs of 22 and 83 compounds were plotted vs. the relative oral bioavailability (AUC solid vs. AUC solution formulation, Frel) in humans and rats, respectively. Furthermore, in order to investigate to what extent Frel rat may predict issues with solubility limited absorption in human, Frel rat was plotted vs. Frel human. Additionally, the impact of bile salts and lecithin on in vitro dissolution of poorly soluble compounds was tested and data compared to Frel rat and human. Respective in vitro - in vivo and in vivo - in vivo correlations were generated and used to build developability criteria. As a result, based on pH-dependent VDAD, Frel rat and in vitro dissolution in simulated intestinal fluid the IR formulation strategy within Pharmaceutical Research and Development organizations can be already set at late stage of drug discovery. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. A pilot study on the serum pharmacokinetics of nattokinase in humans following a single, oral, daily dose.

    Science.gov (United States)

    Ero, Michael Penfield; Ng, Connie M; Mihailovski, Tamara; Harvey, Nathaniel R; Lewis, Brad Howard

    2013-01-01

    Nattokinase is a serine protease and is derived from natto, a traditional Japanese, fermented, soybean food meal. Multiple authors have described the significant fibrinolytic, antithrombotic, and antihypertensive effects of natto. Nattokinase has been growing in popularity for use as a dietary supplement for the benefit of cardiovascular health. Little is known regarding the pharmacokinetic and pharmacodynamic properties of this enzyme, and the bioavailability of nattokinase is currently unknown. This study intended to (1) detect nattokinase directly and immunologically, (2) show that nattokinase and/or its metabolites were detectable in human blood following ingestion of a commercial preparation, and (3) chart a pharmacokinetic dosing effect for nattokinase. The research team designed the pilot study as an in vivo, human clinical trial. Healthy human subjects responded to an advertisement and were screened. Subjects who satisfied both inclusion and exclusion criteria were enrolled into the study. Subjects were then instructed to orally ingest a single capsule containing a known concentration of nattokinase immediately following a baseline blood draw. Subsequent blood draws occurred over a 24-h period. This study was conducted in Oakland, California, at a clinical reference laboratory and was performed with the approval of an institutional review board (IRB) to ensure that appropriate ethical standards were met. Eleven healthy participants (five male, six female, ages 21-65), who met eligibility criteria, were enrolled. Administration of nattokinase occurred orally with the ingestion of a single daily dose (2000 FU) of nattokinase. Capsules, each containing approximately 100 mg of nattokinase, in softgel form (NSK-SD, Japan Bio Science Laboratory, Osaka, Japan), were used in the study. Baseline blood samples were collected, and participants were observed swallowing a single capsule of the nattokinase supplement before returning at 2, 4, 8, 12, 24, and 48 h post

  4. Effects of single oral doses of lysine clonixinate and acetylsalicylic acid on platelet functions in man.

    Science.gov (United States)

    Pallapies, D; Muhs, A; Bertram, L; Rohleder, G; Nagyiványi, P; Peskar, B A

    1996-01-01

    Lysine clonixinate is an analgesic drug with a so far unknown mechanism of action. We have determined its effect on platelet cyclooxygenase in man. Biosynthesis of thromboxane (TX)B2 and prostaglandin (PG)F2 alpha in clotting whole blood ex vivo as well as collagen-induced platelet aggregation measured before and at various time points after oral administration of 125 mg lysine clonixinate were compared to results obtained with 500 mg acetylsalicylic acid (ASA). While biosynthesis of both TXB2 and PGF2 alpha measured radioimmunologically was inhibited significantly 2.5 h, but not 6 h, after administration of lysine clonixinate, inhibition by ASA was much greater and still highly significant after 48 h. Similarly, collagen-induced aggregation of platelet-rich plasma was inhibited for a longer period and to a greater extent after administration of ASA than after lysine clonixinate. Our results indicate that lysine clonixinate is a cyclooxygenase inhibitor of moderate potency. It remains to be investigated whether mechanisms other than inhibition of cyclooxygenase contribute to the analgesic activity of lysine clonixinate.

  5. Enrofloxacin assay validation and pharmacokinetics following a single oral dose in chickens.

    Science.gov (United States)

    da Silva, R G; Reyes, F G R; Sartori, J R; Rath, S

    2006-10-01

    The pharmacokinetics of enrofloxacin (ENRO), a fluoroquinolone antimicrobial agent, was studied in male broiler chickens (Cobb) after single oral administration of 10 mg of ENRO/kg b.w. A high-performance liquid chromatography-photodiode array detector (DAD) (HPLC-DAD) method was developed and validated and used for quantitation of ENRO and its major metabolite ciprofloxacin in plasma. The HPLC analyses were carried out using a cationic-octadecyl mixed column and 0.05 mol/L phosphate buffer (pH 2.5)/acetonitrile as mobile phase. The sample preparation of plasma consisted of the precipitation of proteins followed by solid phase extraction on cationic-octadecyl mixed cartridges. The method was validated considering linear range, linearity, selectivity, sensitivity, limit of detection (LOD), limit of quantitation (LOQ), intra- and inter-day precisions and accuracy. The LOD and LOQ for both fluoroquinolones were 60 and 200 ng/mL for plasma. The plasma concentration vs. time graph was characteristic of a two-compartment open model. The maximal plasma concentration of 1.5 +/- 0.2 mg/mL was achieved at 9 +/- 2 h. The elimination half-life and the mean residence time of ENRO were 1.5 +/- 0.2 and 15.64 h, respectively. The area under the concentration-time curve was calculated as 35 +/- 4 mgxh/mL.

  6. Bevacizumab with metronomic chemotherapy of low-dose oral cyclophosphamide in recurrent cervical cancer: Four cases

    Directory of Open Access Journals (Sweden)

    Rose Isono-Nakata

    2018-05-01

    Full Text Available Standard chemotherapy for women with advanced or recurrent cervical cancer involves a combination of paclitaxel, platinum, and bevacizumab. However, for patients who experience anaphylaxis in response to paclitaxel or platinum, have permanent peripheral neuropathy, or develop early recurrence or progressive disease during first-line chemotherapy, the development of a non-taxane non-platinum regimen is mandatory. Clinical trials using anti-angiogenic treatment demonstrated favorable outcomes in cases of highly vascularized cervical cancer. Metronomic chemotherapy has been considered an anti-angiogenic treatment, although its use in combination with bevacizumab has not been studied in cervical cancer. We treated four patients with recurrent cervical cancer with 50 mg of oral cyclophosphamide daily and 15 mg/kg of intravenous bevacizumab every 3 weeks (CFA-BEV. One patient experienced disease progression after 4 months, whereas the other three patients continued the regimen until their last follow-up at 13, 14, and 15 months, respectively. One patient suffered from grade 3 neutropenia; however, no grade 2 or higher non-hematological toxicities were observed. These cases demonstrate the use of CFA-BEV with minimal toxicity and expected anti-cancer activity and indicate that this regimen should be considered for second-line chemotherapy in advanced recurrent cervical cancer. Keywords: Cervical cancer, Metronomic chemotherapy, Bevacizumab

  7. Comparison of the efficacy and safety of rosuvastatin 10 mg and atorvastatin 20 mg in high-risk patients with hypercholesterolemia – Prospective study to evaluate the Use of Low doses of the Statins Atorvastatin and Rosuvastatin (PULSAR

    Directory of Open Access Journals (Sweden)

    García Hugo

    2006-12-01

    Full Text Available Abstract Background Many patients at high risk of cardiovascular disease do not achieve recommended low-density lipoprotein cholesterol (LDL-C goals. This study compared the efficacy and safety of low doses of rosuvastatin (10 mg and atorvastatin (20 mg in high-risk patients with hypercholesterolemia. Methods A total of 996 patients with hypercholesterolemia (LDL-C ≥ 3.4 and Results Rosuvastatin 10 mg reduced LDL-C levels significantly more than atorvastatin 20 mg at week 6 (44.6% vs. 42.7%, p Conclusion In high-risk patients with hypercholesterolemia, rosuvastatin 10 mg was more efficacious than atorvastatin 20 mg at reducing LDL-C, enabling LDL-C goal achievement and improving other lipid parameters. Both treatments were well tolerated.

  8. Comparing the effects of low-dose contraceptive pills to control dysfunctional uterine bleeding by oral and vaginal methods.

    Science.gov (United States)

    Mehrabian, Ferdous; Abbassi, Fariba

    2013-09-01

    Background and Objective : Contraceptive pills are generally taken orally and can cause side effects such as nausea, vomiting and hypertension. The vaginal use of these pills can reduce such complications. Our objective was to compare the efficacy and side effects of low dose contraceptive pills by oral and vaginal route in the management of dysfunctional uterine bleeding-(DUB) Methods: This comparative observational study was conducted at Beheshti and Alzahra (SA) teaching hospitals, affiliated to Isfahan University of Medical Sciences in 2010-2011. One hundred women who presented with DUB were randomly assigned into two groups of equal number, receiving the low dose oral contraceptive pills by oral or vaginal route for three month. The amount and duration of bleeding were compared at the beginning and at the end of the study and side effects by these two methods compared. The results of this study showed that both oral and vaginal routes effectively reduced the duration and amount of bleeding due to DUB after three courses of treatment. This effect was better in the vaginal method compared with oral administration (P = 0.03). Regarding the side effects, nausea and vomiting were significantly higher in the oral group than in the vaginal group (P = 0.03). Vulvovaginitis infection was more frequent in the vaginal group than in the oral group (P = 0.03). Low dose contraceptive pills are effective in reducing the amount, time, and duration of bleeding in patients with DUB. In addition, reduction of gastrointestinal side effects by vaginal route helps to use these pills by the patient with proper training of physicians, midwives and patients.

  9. Effect of low-dose ritonavir (100 mg twice daily) on the activity of cytochrome P450 2D6 in healthy volunteers

    NARCIS (Netherlands)

    Aarnoutse, Rob E; Kleinnijenhuis, Johanneke; Koopmans, Peter P; Touw, Daan J; Wieling, Jaap; Hekster, Yechiel A; Burger, David M

    2005-01-01

    OBJECTIVE: In the treatment of human immunodeficiency virus infection, the protease inhibitor ritonavir is used in a low dose (100 mg twice daily) to inhibit cytochrome P450 (CYP) 3A4 and thereby increase plasma concentrations of coadministered protease inhibitors. When applied in a therapeutic dose

  10. Effect of low-dose ritonavir (100 mg twice daily) on the activity of cytochrome P450 2D6 in healthy volunteers.

    NARCIS (Netherlands)

    Aarnoutse, R.E.; Kleinnijenhuis, J.; Koopmans †, P.P.; Touw, D.J.; Wieling, J.; Hekster, Y.A.; Burger, D.M.

    2005-01-01

    OBJECTIVE: In the treatment of human immunodeficiency virus infection, the protease inhibitor ritonavir is used in a low dose (100 mg twice daily) to inhibit cytochrome P450 (CYP) 3A4 and thereby increase plasma concentrations of coadministered protease inhibitors. When applied in a therapeutic dose

  11. Resolution of methylphenidate osmotic release oral system-induced hair loss in two siblings after dose escalation.

    Science.gov (United States)

    Ardic, Ulku Akyol; Ercan, Eyup Sabri

    2017-11-01

    This report describes the cases of two siblings who experienced hair loss after treatment with methylphenidate (MPH) osmotic release oral system (OROS). Hair loss was resolved after discontinuation of the drug, but the children re-initiated treatment, after which hair loss again occurred, but they continued the treatment. After dose escalation, the hair loss resolved. This is the first report to describe resolution of OROS-MPH-induced hair loss after dose escalation. © 2017 Japan Pediatric Society.

  12. Evaluation of a low-dose CT protocol with oral contrast for assessment of acute appendicitis

    Energy Technology Data Exchange (ETDEWEB)

    Platon, Alexandra; Jlassi, Helmi; Becker, Christoph D.; Poletti, Pierre-Alexandre [University Hospital of Geneva, Department of Radiology, Geneva 14 (Switzerland); Rutschmann, Olivier T. [University Hospital of Geneva, Emergency Center, Geneva (Switzerland); Verdun, Francis R. [University Institute for Radiation Physics, Lausanne (Switzerland); Gervaz, Pascal [University Hospital of Geneva, Clinic of Digestive Surgery, Geneva (Switzerland)

    2009-02-15

    The aim of this study was to evaluate a low-dose CT with oral contrast medium (LDCT) for the diagnosis of acute appendicitis and compare its performance with standard-dose i.v. contrast-enhanced CT (standard CT) according to patients' BMIs. Eighty-six consecutive patients admitted with suspicion of acute appendicitis underwent LDCT (30 mAs), followed by standard CT (180 mAs). Both examinations were reviewed by two experienced radiologists for direct and indirect signs of appendicitis. Clinical and surgical follow-up was considered as the reference standard. Appendicitis was confirmed by surgery in 37 (43%) of the 86 patients. Twenty-nine (34%) patients eventually had an alternative discharge diagnosis to explain their abdominal pain. Clinical and biological follow-up was uneventful in 20 (23%) patients. LDCT and standard CT had the same sensitivity (100%, 33/33) and specificity (98%, 45/46) to diagnose appendicitis in patients with a body mass index (BMI) {>=} 18.5. In slim patients (BMI < 18.5), sensitivity to diagnose appendicitis was 50% (2/4) for LDCT and 100% (4/4) for standard CT, while specificity was identical for both techniques (67%, 2/3). LDCT may play a role in the diagnostic workup of patients with a BMI {>=} 18.5. (orig.)

  13. Evaluation of a low-dose CT protocol with oral contrast for assessment of acute appendicitis

    International Nuclear Information System (INIS)

    Platon, Alexandra; Jlassi, Helmi; Becker, Christoph D.; Poletti, Pierre-Alexandre; Rutschmann, Olivier T.; Verdun, Francis R.; Gervaz, Pascal

    2009-01-01

    The aim of this study was to evaluate a low-dose CT with oral contrast medium (LDCT) for the diagnosis of acute appendicitis and compare its performance with standard-dose i.v. contrast-enhanced CT (standard CT) according to patients' BMIs. Eighty-six consecutive patients admitted with suspicion of acute appendicitis underwent LDCT (30 mAs), followed by standard CT (180 mAs). Both examinations were reviewed by two experienced radiologists for direct and indirect signs of appendicitis. Clinical and surgical follow-up was considered as the reference standard. Appendicitis was confirmed by surgery in 37 (43%) of the 86 patients. Twenty-nine (34%) patients eventually had an alternative discharge diagnosis to explain their abdominal pain. Clinical and biological follow-up was uneventful in 20 (23%) patients. LDCT and standard CT had the same sensitivity (100%, 33/33) and specificity (98%, 45/46) to diagnose appendicitis in patients with a body mass index (BMI) ≥ 18.5. In slim patients (BMI < 18.5), sensitivity to diagnose appendicitis was 50% (2/4) for LDCT and 100% (4/4) for standard CT, while specificity was identical for both techniques (67%, 2/3). LDCT may play a role in the diagnostic workup of patients with a BMI ≥ 18.5. (orig.)

  14. Effect of a single oral dose of milrinone on left ventricular diastolic performance in the failing human heart

    NARCIS (Netherlands)

    F. Piscione; B.E. Jaski; G.J. Wenting (Gert); P.W.J.C. Serruys (Patrick)

    1987-01-01

    textabstractIn 14 patients with severe congestive heart failure, left ventricular pressure (measured by tip manometer) and derived variables were measured before and every 10 minutes after administration of oral milrinone (10 mg) for 50 minutes along with measurements of coronary sinus blood flow

  15. Oral glucose tolerance test performance in olanzapine-treated schizophrenia-spectrum patients is predicted by BMI and triglycerides but not olanzapine dose or duration.

    Science.gov (United States)

    Guina, Jeffrey; Roy, Sayon; Gupta, Ankur; Langleben, Daniel D; Elman, Igor

    2017-07-01

    Olanzapine, an atypical antipsychotic, is associated with glucoregulatory abnormalities, but the nature of this link is not fully elucidated. This is the first olanzapine oral glucose tolerance test (oGTT) study to consider treatment dose and duration, and to compare complementary indices respectively assessing insulin sensitivity (Matsuda index) and resistance (homeostasis model assessment). Body mass index (BMI), body composition, plasma lipids, and oGTT were measured in olanzapine-treated nondiabetic patients with DSM-IV-TR diagnosis of schizophrenia or schizoaffective disorder (n = 35). While only one previously undiagnosed participant met diabetes criteria based on fasting plasma glucose alone (≥126 mg/dL), seven were diagnosed with oGTT (2-hr plasma glucose ≥200 mg/dL). Multiple regression analyses revealed that the Matsuda index correlated with BMI (p triglycerides (p = 0.01), but not with age, olanzapine dose, olanzapine treatment duration, or plasma cholesterol. Homeostasis model assessment and fasting plasma glucose correlated with triglycerides only (p triglycerides may be implicated in olanzapine-related glucoregulatory abnormalities. The lack of correlation between glucoregulatory abnormalities and olanzapine dose or treatment duration suggests preexisting metabolic disturbances and/or disturbances arising early in the course of treatment. Clinicians prescribing antipsychotics should consider oGTT, especially in patients with obesity and/or hypertriglyceridemia. Copyright © 2017 John Wiley & Sons, Ltd.

  16. The Impact of a One-Dose versus Two-Dose Oral Cholera Vaccine Regimen in Outbreak Settings: A Modeling Study.

    Directory of Open Access Journals (Sweden)

    Andrew S Azman

    2015-08-01

    Full Text Available In 2013, a stockpile of oral cholera vaccine (OCV was created for use in outbreak response, but vaccine availability remains severely limited. Innovative strategies are needed to maximize the health impact and minimize the logistical barriers to using available vaccine. Here we ask under what conditions the use of one dose rather than the internationally licensed two-dose protocol may do both.Using mathematical models we determined the minimum relative single-dose efficacy (MRSE at which single-dose reactive campaigns are expected to be as or more effective than two-dose campaigns with the same amount of vaccine. Average one- and two-dose OCV effectiveness was estimated from published literature and compared to the MRSE. Results were applied to recent outbreaks in Haiti, Zimbabwe, and Guinea using stochastic simulations to illustrate the potential impact of one- and two-dose campaigns. At the start of an epidemic, a single dose must be 35%-56% as efficacious as two doses to avert the same number of cases with a fixed amount of vaccine (i.e., MRSE between 35% and 56%. This threshold decreases as vaccination is delayed. Short-term OCV effectiveness is estimated to be 77% (95% CI 57%-88% for two doses and 44% (95% CI -27% to 76% for one dose. This results in a one-dose relative efficacy estimate of 57% (interquartile range 13%-88%, which is above conservative MRSE estimates. Using our best estimates of one- and two-dose efficacy, we projected that a single-dose reactive campaign could have prevented 70,584 (95% prediction interval [PI] 55,943-86,205 cases in Zimbabwe, 78,317 (95% PI 57,435-100,150 in Port-au-Prince, Haiti, and 2,826 (95% PI 2,490-3,170 cases in Conakry, Guinea: 1.1 to 1.2 times as many as a two-dose campaign. While extensive sensitivity analyses were performed, our projections of cases averted in past epidemics are based on severely limited single-dose efficacy data and may not fully capture uncertainty due to imperfect

  17. Pharmacokinetic interaction of enrofloxacin/trimethoprim combination following single-dose intraperitoneal and oral administration in rats.

    Science.gov (United States)

    Choi, Myung-Jin; Yohannes, Sileshi Belew; Lee, Seung-Jin; Damte, Dereje; Kim, Jong-Choon; Suh, Joo-Won; Park, Seung-Chun

    2014-03-01

    The pharmacokinetic interaction of enrofloxacin and trimethoprim was evaluated after single-dose intraperitoneal or oral co-administration in rats. Plasma concentrations of the two drugs were determined by high-performance liquid chromatography. Following intraperitoneal combination, a significant (P trimethoprim, respectively. There was a significant (P trimethoprim. Further study is recommended in other species of animals.

  18. Non-randomized study on the effects of preoperative radiotherapy and daily administration of low-dose cisplatin against those of radiotherapy alone for oral cancer. Effects on local control, control of metastases, and overall survival

    International Nuclear Information System (INIS)

    Kurita, Hiroshi; Ohtsuka, Akiko; Kobayashi, Hiroichi; Kurashina, Kenji; Shikama, Naoto; Oguchi, Masahiko

    2000-01-01

    Cisplatin is a known radiation modifier. Our previous study suggested that daily administration of low-dose cisplatin enhanced the efficacy of radiotherapy against primary oral squamous carcinoma. In this paper, we follow the patients who participated in the previous study and survey the benefit of combination low-dose cisplatin in improving local control, prevention of metastases, and overall survival. This study included patients with surgically resectable advanced oral tumors. Ten patients underwent preoperative radiotherapy of 30-40 Gy/15-20 days with concomitant daily administration of low-dose cisplatin (5 mg/body or 5 mg/m 2 ). Ten other patients received external radiotherapy alone. All patients then underwent a planned radical tumor resection. No significant difference was see in loco-regional control rates (primary: 86 vs. 88%, neck: 83 vs. 78% at 48 months) or incidence of metastasis (70 vs. 64%) between the two groups. Nor was there a significant difference in the overall survival rate (60 vs. 66%). The results of this study suggest that the concomitant use of daily administration of low-dose cisplatin with preoperative radiation brings no statistically significant benefit in improving local control and survival rate in patients with advanced resectable oral cancer. (author)

  19. Risk of venous thromboembolism from use of oral contraceptives containing different progestogens and oestrogen doses: Danish cohort study, 2001-9

    DEFF Research Database (Denmark)

    Lidegaard, Øjvind; Nielsen, Lars Hougaard; Skovlund, Charlotte Wessel

    2011-01-01

    To assess the risk of venous thromboembolism from use of combined oral contraceptives according to progestogen type and oestrogen dose.......To assess the risk of venous thromboembolism from use of combined oral contraceptives according to progestogen type and oestrogen dose....

  20. A Randomised Trial Evaluating the Safety and Immunogenicity of the Novel Single Oral Dose Typhoid Vaccine M01ZH09 in Healthy Vietnamese Children

    NARCIS (Netherlands)

    Tran, T.H.; Nguyen, T.D.; Nguyen, T.T.; Ninh, T.T.V.; Tran, N.B.C.; Nguyen, V.M.H.; Tran, T.T.N.; Cao, T.T.; Pham, V.M.; Nguyen, T.C.B.; Tran, T.D.H.; Pham, V.T.; To, S.D.; Campbell, J.I.; Stockwell, E.; Schultsz, C.; Simmons, C.P.; Glover, C.; Lam, W.; Marques, F.; May, J.P.; Upton, A.; Budhram, R.; Dougan, G.; Farrar, J.; Nguyen, V.V.C.; Dolecek, C.

    2010-01-01

    Background: The emergence of drug resistant typhoid fever is a major public health problem, especially in Asia. An oral single dose typhoid vaccine would have major advantages. M01ZH09 is a live oral single dose candidate typhoid vaccine containing Salmonella enterica serovar Typhi (Ty2 aroC(-)

  1. A randomised trial evaluating the safety and immunogenicity of the novel single oral dose typhoid vaccine M01ZH09 in healthy Vietnamese children

    NARCIS (Netherlands)

    Tran, Tinh Hien; Nguyen, Thi Dung; Nguyen, Thanh Truong; Ninh, Thi Thanh Van; Tran, Nguyen Bich Chau; Nguyen, Van Minh Hoang; Tran, Thi Thu Nga; Cao, Thu Thuy; Pham, Van Minh; Nguyen, Thi Cam Binh; Tran, Thi Diem Ha; Pham, Van Toi; To, Song Diep; Campbell, James I.; Stockwell, Elaine; Schultsz, Constance; Simmons, Cameron P.; Glover, Clare; Lam, Winnie; Marques, Filipe; May, James P.; Upton, Anthony; Budhram, Ronald; Dougan, Gordon; Farrar, Jeremy; Nguyen, Van Vinh Chau; Dolecek, Christiane

    2010-01-01

    The emergence of drug resistant typhoid fever is a major public health problem, especially in Asia. An oral single dose typhoid vaccine would have major advantages. M01ZH09 is a live oral single dose candidate typhoid vaccine containing Salmonella enterica serovar Typhi (Ty2 aroC(-)ssaV(-)) ZH9 with

  2. Evaluation of changes in serum chemistry in association with feed withdrawal or high dose oral gavage with Dextran Sodium Sulfate (DSS) induced gut leakage in broiler chickens

    Science.gov (United States)

    Dextran sodium sulfate (DSS) has been shown to be effective at inducing enteric inflammation in broiler chickens, resulting in increased leakage of orally administered fluorescein isothiocyanate dextran to circulation. In a previous study, two doses of DSS (0.45g/dose) administered as oral gavage re...

  3. Microdosing clinical study: pharmacokinetic, pharmacogenomic (SLCO2B1), and interaction (grapefruit juice) profiles of celiprolol following the oral microdose and therapeutic dose.

    Science.gov (United States)

    Ieiri, Ichiro; Doi, Yohei; Maeda, Kazuya; Sasaki, Tomohiro; Kimura, Miyuki; Hirota, Takeshi; Chiyoda, Takeshi; Miyagawa, Mayuko; Irie, Shin; Iwasaki, Kazuhide; Sugiyama, Yuichi

    2012-07-01

    The authors evaluated the contribution of the SLCO2B1 polymorphism to the pharmacokinetics of celiprolol at a microdose (MD) and therapeutic dose (TD) and compared pharmacokinetic proportionality between the 2 dose forms in 30 SLCO2B1 genotype-matched healthy volunteers. Three drugs (celiprolol, fexofenadine, and atenolol) were orally administered as a cassette dosing following the MD (totally 97.5 µg) and then a TD (100 mg) of celiprolol, with and without grapefruit juice. The mean AUC(0-24) of celiprolol was lower in SLCO2B1*3/*3 individuals (775 ng·h/mL) than in *1/*3 (1097 ng·h/mL) and *1/*1 (1547 ng·h/mL) individuals following the TD, and this was confirmed in population pharmacokinetic analysis with statistical significances; however, SLCO2B1 genotype-dependent differences disappeared following the MD. Dose-normalized AUC of celiprolol at the MD was much lower than that at the TD, explained by the saturation of the efflux transporter. Thus, the effect of SLCO2B1 polymorphism on the AUC of celiprolol clearly observed only at the TD may be due to the saturation of the efflux transport systems.

  4. Treatment outcome with low-dose-rate interstitial brachytherapy in early-stage oral tongue cancers

    Directory of Open Access Journals (Sweden)

    Bhalavat Rajendra

    2009-01-01

    Full Text Available Purpose : Although radical radiotherapy is known to be equally effective for early-stage oral tongue cancers (T1-2 N0 with the added advantage of organ and function preservation, surgery remains the preferred treatment. We present outcome of patients treated with brachytherapy (BT either radical or boost. Materials and Methods : Fifty-seven patients (T1/T2 31/26 were studied. Seventeen patients (30% were treated with radical BT (50-67 Gy while 40 (70% with external beam radiation therapy (EBRT + BT (36-56 Gy + 15-38 Gy]. Low-dose-rate (LDR BT was delivered with 192 Ir wires, using plastic bead technique with varied dose rates (< 60 cGy/h in 29 patients, 60-90 cGy/h in 17, and> 90 cGy/h in 11. Results : The overall local control (LCR was achieved in 59.7% (34/57 patients. LCR for T1 and T2 was 67.8% and 50%, respectively. A total of 23 patients had failures [local: 20 (T1: 8; T2: 12 patients, node: 5 (T1:2; T2: 3, and local + nodal: 3]. Overall 5-year disease-free survival and overall survival (OAS were 51% and 67%, respectively and those for T1 and T2 was 64.5/77.4% and 38.5/54% respectively (P = 0.002. All 16 patients were salvaged. Median survival after salvage treatment was 13.5 months (6-100 months. Soft tissue necrosis was observed in 12.3% (7/57 and osteoradionecrosis in two patients. Conclusion : BT, as an integral part of radical radiation therapy in early-stage tongue cancers, appears to be an effective alternative treatment modality with preservation of the organ and function without jeopardizing the outcome.

  5. Phase III trial of high and low dose rate interstitial radiotherapy for early oral tongue cancer

    International Nuclear Information System (INIS)

    Inoue, Takehiro; Inoue, Toshihiko; Teshima, Teruki; Murayama, Shigeyuki; Shimizutani, Kimishige; Fuchihata, Hajime; Furukawa, Souhei

    1996-01-01

    Purpose: Oral tongue carcinomas are highly curable with radiotherapy. In the past, patients with tongue carcinoma have usually been treated with low dose rate (LDR) interstitial radiation. This Phase III study was designed to compare the treatment results obtained with LDR with those obtained with high dose rate (HDR) interstitial radiotherapy for tongue carcinoma. Methods and Materials: The criteria for patient selection for the Phase III study were: (a) presence of a T1T2N0 tumor that could be treated with single-plane implantation, (b) localization of tumor at the lateral tongue border, (c) tumor thickness of 10 mm or less, (d) performance status between O and 3, and (e) absence of any severe concurrent disease. From April 1992 through December 1993, 15 patients in the LDR group (70 Gy/4 to 9 days) and 14 patients in the HDR group (60 Gy/10 fractions/6 days) were accrued. The time interval between two fractions of the HDR brachytherapy was more than 6 h. Results: Local recurrence occurred in two patients treated with LDR brachytherapy but in none of the patients treated with HDR. One- and 2-year local control rates for patients in the LDR group were both 86%, compared with 100% in the HDR group (p = 0.157). There were four patients with nodal metastasis in the LDR group and three in the HDR group. Local recurrence occurred in two of the four patients with nodal metastases in the LDR group. One- and 2-year nodal control rates for patients in the LDR group are were 85%, compared with 79% in the HDR group. Conclusion: HDR fractionated interstitial brachytherapy can be an alternative to traditional LDR brachytherapy for early tongue cancer and eliminate the radiation exposure for medical staffs

  6. Importance of levonorgestrel dose in oral contraceptives for effects on coagulation

    NARCIS (Netherlands)

    Kluft, C.; Maat, M.P.M. de; Heinemann, L.A.J.; Spannagl, M.; Schramm, W.

    1999-01-01

    Combined oral contraceptives show clear differences in effect on the tissue factor-initiated coagulation test of activated protein C resistance, which is dependent on the presence and dosage of levonorgestrel. Multiphasic levonorgestrol oral contraceptives differ from monophasic contraceptives and

  7. Toxicokinetics and toxicological effects of single oral dose of fumonisin B1 containing Fusarium verticillioides culture material in weaned piglets.

    Science.gov (United States)

    Dilkin, P; Direito, G; Simas, M M S; Mallmann, C A; Corrêa, B

    2010-05-14

    Toxicokinetics and the toxicological effects of culture material containing fumonisin B(1) (FB(1)) were studied in male weaned piglets by clinical, pathological, biochemical and sphingolipid analyses. The animals received a single oral dose of 5 mg FB(1)/kg of body weight, obtained from Fusarium verticillioides culture material. FB(1) was detected by HPLC in plasma collected at 1-h intervals up to 6h and at 12-h intervals up to 96 h. FB(1) eliminated in feces and urine was quantified over a 96-h period and in liver samples collected 96 h post-intoxication. Blood samples were obtained at the beginning and end of the experiment to determine serum enzyme activity, total bilirubin, cholesterol, sphinganine (Sa), sphingosine (So) and the Sa/So ratio. FB(1) was detected in plasma between 30 min and 36 h after administration. The highest concentration of FB(1) was observed after 2 h, with a mean concentration of 282 microg/ml. Only 0.93% of the total FB(1) was detected in urine between 75 min and 41 h after administration, the highest mean concentration (561 microg/ml) was observed during the interval after 8 at 24 h. Approximately 76.5% of FB(1) was detected in feces eliminated between 8 and 84 h after administration, with the highest levels observed between 8 and 24 h. Considering the biochemical parameters, a significant increase only occurred in cholesterol, alkaline phosphatase and aspartate aminotransferase activities. In plasma and urine, the highest Sa and Sa/So ratios were obtained at 12 and 48 h, respectively. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

  8. Bioavailability and Pharmacokinetics of Oral Cocaine in Humans.

    Science.gov (United States)

    Coe, Marion A; Jufer Phipps, Rebecca A; Cone, Edward J; Walsh, Sharon L

    2018-06-01

    The pharmacokinetic profile of oral cocaine has not been fully characterized and prospective data on oral bioavailability are limited. A within-subject study was performed to characterize the bioavailability and pharmacokinetics of oral cocaine. Fourteen healthy inpatient participants (six males) with current histories of cocaine use were administered two oral doses (100 and 200 mg) and one intravenous (IV) dose (40 mg) of cocaine during three separate dosing sessions. Plasma samples were collected for up to 24 h after dosing and analyzed for cocaine and metabolites by gas chromatography-mass spectrometry. Pharmacokinetic parameters were calculated by non-compartmental analysis, and a two-factor model was used to assess for dose and sex differences. The mean ± SEM oral cocaine bioavailability was 0.32 ± 0.04 after 100 and 0.45 ± 0.06 after 200 mg oral cocaine. Volume of distribution (Vd) and clearance (CL) were both greatest after 100 mg oral (Vd = 4.2 L/kg; CL = 116.2 mL/[min kg]) compared to 200 mg oral (Vd = 2.9 L/kg; CL = 87.5 mL/[min kg]) and 40 mg IV (Vd = 1.3 L/kg; CL = 32.7 mL/[min kg]). Oral cocaine area-under-thecurve (AUC) and peak concentration increased in a dose-related manner. AUC metabolite-to-parent ratios of benzoylecgonine and ecgonine methyl ester were significantly higher after oral compared to IV administration and highest after the lower oral dose. In addition, minor metabolites were detected in higher concentrations after oral compared to IV cocaine. Oral cocaine produced a pharmacokinetic profile different from IV cocaine, which appears as a rightward and downward shift in the concentration-time profile. Cocaine bioavailability values were similar to previous estimates. Oral cocaine also produced a unique metabolic profile, with greater concentrations of major and minor metabolites.

  9. Co-crystal of Tramadol-Celecoxib in Patients with Moderate to Severe Acute Post-surgical Oral Pain: A Dose-Finding, Randomised, Double-Blind, Placebo- and Active-Controlled, Multicentre, Phase II Trial.

    Science.gov (United States)

    López-Cedrún, José; Videla, Sebastián; Burgueño, Miguel; Juárez, Inma; Aboul-Hosn, Samir; Martín-Granizo, Rafael; Grau, Joan; Puche, Miguel; Gil-Diez, José-Luis; Hueto, José-Antonio; Vaqué, Anna; Sust, Mariano; Plata-Salamán, Carlos; Monner, Antoni

    2018-06-01

    Co-crystal of tramadol-celecoxib (CTC), containing equimolar quantities of the active pharmaceutical ingredients (APIs) tramadol and celecoxib (100 mg CTC = 44 mg rac-tramadol hydrochloride and 56 mg celecoxib), is a novel API-API co-crystal for the treatment of pain. We aimed to establish the effective dose of CTC for treating acute pain following oral surgery. A dose-finding, double-blind, randomised, placebo- and active-controlled, multicentre (nine Spanish hospitals), phase II study (EudraCT number: 2011-002778-21) was performed in male and female patients aged ≥ 18 years experiencing moderate to severe pain following extraction of two or more impacted third molars requiring bone removal. Eligible patients were randomised via a computer-generated list to receive one of six single-dose treatments (CTC 50, 100, 150, 200 mg; tramadol 100 mg; and placebo). The primary efficacy endpoint was the sum of pain intensity difference (SPID) over 8 h assessed in the per-protocol population. Between 10 February 2012 and 13 February 2013, 334 patients were randomised and received study treatment: 50 mg (n = 55), 100 mg (n = 53), 150 mg (n = 57), or 200 mg (n = 57) of CTC, 100 mg tramadol (n = 58), or placebo (n = 54). CTC 100, 150, and 200 mg showed significantly higher efficacy compared with placebo and/or tramadol in all measures: SPID (0-8 h) (mean [standard deviation]): - 90 (234), - 139 (227), - 173 (224), 71 (213), and 22 (228), respectively. The proportion of patients experiencing treatment-emergent adverse events was lower in the 50 (12.7% [n = 7]), 100 (11.3% [n = 6]), and 150 (15.8% [n = 9]) mg CTC groups, and similar in the 200 mg (29.8% [n = 17]) CTC group, compared with the tramadol group (29.3% [n = 17]), with nausea, dizziness, and vomiting the most frequent events. Significant improvement in the benefit-risk ratio was observed for CTC (doses ≥ 100 mg) over tramadol and placebo in

  10. Intralesional Versus Oral Chloroquine in Cutaneous Leishmaniasis: Comparison of Outcome, Duration of Treatment and Total Dose of Drug

    International Nuclear Information System (INIS)

    Hanif, M. M.; Akram, K.; Mustafa, G.

    2016-01-01

    Objective: To compare intralesional versus oral chloroquine in cutaneous leishmaniasis and determine the cure rate, duration of treatment, and total dose of drug. Study Design: Randomized controlled study. Place and Duration of Study: Department of Dermatology, Sheikh Zayed Medical College/Hospital, Rahim Yar Khan, from November 2013 to June 2014. Methodology: Consecutive 86 patients of cutaneous leishmaniasis, with single to multiple lesions of various sizes were enrolled and divided randomly into group A and B for the purpose of intralesional and oral chloroquine administration, respectively to compare the effect of the two routes on duration of treatment and total dose of the drug. SPSS version 16 was used for data analysis after data entry into it. Quantitative variables like, duration, cost and total dose of treatment were calculated as mean and standard deviation and compared by using T-test. P-value of less than 0.05 was taken as significant. Results: Cure rate was 100% in both groups towards the end of treatment. Mean duration of treatment was 9.17 ± 3 weeks in intralesional (A) group as against 11.37 ± 3 weeks in oral (B) group (p = 0.0028). Mean total dose of the drug given to each patient in group A was 5.8 ± 0.5 gm and in group B, it was 19.2 ± 1.5 gm, which is significantly higher (p=0.001). The total cost of treatment in group A was Rs. 90 ± 8 and in group B it was Rs. 91 ± 1 (p=0.446). Conclusion: Duration of treatment is significantly shorter and total dose is lesser with intralesional compared to oral chloroquine in treatment of cutaneous leishmaniasis. (author)

  11. [Safety Evaluation of Rare Sugar Syrup: Single-dose Oral Toxicity in Rats, Reverse Mutation Assay, Chromosome Aberration Assay, and Acute Non-Effect Level for Diarrhea of a Single Dose in Humans].

    Science.gov (United States)

    Yamada, Takako; Iida, Tetsuo; Takamine, Satoshi; Hayashi, Noriko; Okuma, Kazuhiro

    2015-01-01

    The safety of rare sugar syrup obtained from high-fructose corn syrup under slightly alkaline conditions was studied. Mutagenicity of rare sugar syrup was assessed by a reverse mutation assay using Salmonella typhimurium and Escherichia coli, and an in vitro chromosomal aberration assay using Chinese hamster lung cell line (CHL/IU). No mutagenicity of rare sugar syrup was detected under these experimental conditions. Oral administration of single dose (15,000 mg/kg) of rare sugar syrup to rats caused no abnormalities, suggesting no adverse effect of rare sugar syrup. In humans, the acute non-effect level of rare sugar syrup for causing diarrhea was estimated as 0.9 g/kg body weight as dry solid base in both males and females.

  12. Comparison of a single-dose vectored thermal pulsation procedure with a 3-month course of daily oral doxycycline for moderate-to-severe meibomian gland dysfunction.

    Science.gov (United States)

    Hagen, Kerry B; Bedi, Raman; Blackie, Caroline A; Christenson-Akagi, Kellie J

    2018-01-01

    The aim of this study was to compare the efficacy of a single bilateral 12-minute vectored thermal pulsation (VTP) procedure versus daily oral doxycycline for 3 months for moderate-to-severe meibomian gland dysfunction (MGD). This prospective, randomized, parallel-group, single-masked study included 28 subjects who received either a single-dose VTP or 3 months of doxycycline treatment. At baseline and 3 months post treatment, all subjects were evaluated for the following: dry eye symptoms with a standard dry eye questionnaire (the Standard Patient Evaluation for Eye Dryness [SPEED]), meibomian gland (MG) function by counting the number of glands yielding liquid secretion with the MG evaluator (MGE), tear breakup time (TBUT) and corneal and conjunctival staining. In the VTP group, at 3 months, there was a significant improvement in MG function (4.00±1.47 to 7.73±5.53), SPEED score (11.00±3.30 to 5.42±2.15), TBUT (6.26±2.01 to 8.44±1.81), corneal staining (0.38±0.50 to 0.12±0.33) and conjunctival staining (1.69±1.93 to 0.62±0.85). In the doxycycline group, there was a significant improvement in MG function (4.63±1.41 to 10.63±5.91), SPEED score (13.42±4.17 to 9.42±5.47) and conjunctival staining (2.38±1.88 to 1.13±1.51), but the improvement in TBUT (6.90±2.56 to 7.59±2.03) and corneal staining (0.21±0.41 to 0.13±0.34) was not statistically significant ( p =0.262 and p =0.414, respectively). At 3 months, SPEED score was significantly better in the VTP group ( p oral doxycycline at improving the dry eye symptoms secondary to MGD. A single 12-minute VTP treatment was at least as effective as a dose of doxycycline for 3 months, in improving MG function and all measured signs of MGD. Given the minimal risk profile of the single VTP procedure over long-term doxycycline use, a single VTP presents a favorable alternative to long-term antibiotic use.

  13. The effects of oral and intramuscular administration and dose escalation of enrofloxacin on the selection of quinolone resistance among Salmonella and coliforms in pigs

    DEFF Research Database (Denmark)

    Wiuff, C.; Lykkesfeldt, J.; Svendsen, O.

    2003-01-01

    The effect of route of administration and dose of enrofloxacin (Baytril(R)) on the development of fluoroquinolone resistance in Salmonella and Escherichia coli in the intestinal tract of pigs was investigated. Healthy pigs at the age of 8-10 weeks were infected with a mixture of susceptible wild......-type (MICciprofloxacin = 0.03 mug/ml) and a mutant Salmonella typhimurium with reduced susceptibility to fluoroquinolones (MICciprofloxacin 0.5 mug/ml) (in the ratio 99: 1) and treated with 2.5 mg/kg bwt enrofloxacin by either intramuscular (i.m.) or oral (p.o.) administration at time points either 4 or 24 It after....... The Salmonella infection was cleared in all cases during the 2 weeks independent of frequency of resistance. The study showed that resistance is very easily selected by treatment with enrofloxacin at the recommended dose 2.5 mg/kg bwt, but also that the intensity of selection can be reduced by using...

  14. Efeitos da associação entre pequenas doses subaracnóideas de morfina e cetoprofeno venoso e oral em pacientes submetidas à cesariana Efectos de la asociación entre pequeñas dosis subaracnóideas de morfina y cetoprofeno venoso y oral en pacientes sometidas a cesariana Effects of low spinal morphine doses associated to intravenous and oral ketoprofen in patients submitted to cesarean sections

    Directory of Open Access Journals (Sweden)

    Eliana Marisa Ganem

    2003-08-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: Pequenas doses subaracnóideas de morfina são eficazes em reduzir a dor pós-operatória de pacientes submetidas à cesariana, com menor incidência de efeitos colaterais. O objetivo desta pesquisa foi avaliar a qualidade da analgesia pós-operatória e a ocorrência de efeitos colaterais em pacientes submetidas a cesarianas, sob anestesia subaracnóidea com bupivacaína hiperbárica e morfina nas doses de 0,05 mg e 0,1 mg, associadas ao cetoprofeno pelas vias venosa e oral. MÉTODO: Participaram do estudo 60 gestantes de termo, estado físico ASA I e II, que foram submetidas à cesariana eletiva. As pacientes foram divididas em dois grupos: grupo 1 - morfina 0,1 mg, grupo 2 - 0,05 mg, associada a 15 mg de bupivacaína hiperbárica. Todas receberam cetoprofeno (100 mg por via venosa no per-operatório e por via oral a cada 8 horas no primeiro dia de pós-operatório. As pacientes foram avaliadas 6, 12 e 24 horas após o término da cirurgia, com relação à intensidade da dor e presença de efeitos colaterais (sedação, prurido, náusea e vômito. A presença destes últimos também foi avaliada no per-operatório. RESULTADOS: Ambos os grupos foram idênticos quanto aos dados antropométricos e à duração da cirurgia e da anestesia. Também foram homogêneos com relação à intensidade da dor pós-operatória e à presença de prurido, sedação, náusea e vômito. CONCLUSÕES: A morfina, nas doses de 0,05 mg e 0,1 mg administradas no espaço subaracnóideo, associada ao cetoprofeno pelas vias venosa e oral, apresentou a mesma qualidade de analgesia pós-operatória e determinou a mesma ocorrência de efeitos colaterais.JUSTIFICATIVA Y OBJETIVOS: Pequeñas dosis subaracnóideas de morfina son eficaces en reducir el dolor pos-operatorio de pacientes sometidas a cesariana, con menor incidencia de efectos colaterales. El objetivo de esta pesquisa fue evaluar la calidad de la analgesia pos-operatoria y la ocurrencia

  15. Challenging the neuronal MIBG uptake by pharmacological intervention: effect of a single dose of oral amitriptyline on regional cardiac MIBG uptake

    Energy Technology Data Exchange (ETDEWEB)

    Estorch, Montserrat; Carrio, Ignasi; Mena, Esther; Flotats, Albert; Camacho, Valle; Fuertes, Jordi [Autonomous University of Barcelona, Department of Nuclear Medicine, Hospital Sant Pau, Barcelona (Spain); Kulisewsky, Jaume [Autonomous University of Barcelona, Department of Neurology, Hospital Sant Pau, Barcelona (Spain); Narula, Jagat [Irvine College of Medicine, Division of Cardiology, University of California, Irvine, CA (United States)

    2004-12-01

    Imaging with metaiodobenzylguanidine (MIBG) is used for the assessment of neuronal dysfunction in various cardiovascular disorders. Although valuable information is obtained by resting MIBG imaging, it is conceivable that competitive interference with the re-uptake mechanism would exaggerate MIBG defects and might unmask subclinical neuronal dysfunction. Tricyclic antidepressants, such as amitriptyline, have been reported to significantly increase cardiac MIBG washout and inhibit uptake into presynaptic neurons. This study was undertaken to assess whether a single oral dose of amitriptyline could influence cardiac MIBG distribution. Six patients (aged 62-81 years; four males, two females) who had demonstrated a normal cardiac MIBG scan during work-up for movement disorders were studied. The patients underwent a second {sup 123}I-MIBG study after oral administration of 25 mg amitriptyline within 1 week. Single-photon emission computed tomography images were acquired at 4 h to assess the regional distribution of MIBG, after generation of polar maps and employing a 20-segment model. Mean percentage of peak activity was calculated for each segment at rest and after amitriptyline administration. After amitriptyline administration, there was a decrease in regional MIBG uptake in 10{+-}4 segments per patient [62/120 segments (52%): 37 segments with a 5-10% decrease, 25 segments with a >10% decrease]. This change was statistically significant in lateral (P=0.003), apical (P<0.0001) and inferior (P=0.03) regions. A single oral dose of amitriptyline can induce changes in the uptake and retention of cardiac MIBG, indicating the feasibility of use of pharmacological intervention in cardiac neurotransmission imaging. (orig.)

  16. Exploratory pilot study assessing the risk of cognitive impairment or sedation in the elderly following single doses of solifenacin 10 mg.

    Science.gov (United States)

    Wesnes, Keith A; Edgar, Chris; Tretter, Reiner N; Bolodeoku, John

    2009-11-01

    To assess the cognitive effects of single doses of solifenacin 10 mg compared with placebo (primary objective) and oxybutynin immediate release (IR) 10 mg (secondary objective) in elderly subjects. Single-centre, randomised, double-blind, placebo-controlled study in 12 healthy elderly volunteers, with three crossover periods separated by two 14-day washout periods. Each sequence consisted of a single dose of solifenacin 10 mg in one period, oxybutynin IR 10 mg in another and placebo in another. Aspects of attention, information processing, working memory, episodic memory and self-rated mood and alertness were tested using the validated Cognitive Drug Research computerised assessment system. There was no evidence from absolute mean values or changes from baseline to suggest that solifenacin 10 mg impaired cognition or self-ratings of mood and alertness versus placebo. Post-hoc ANCOVA showed no statistically significant cognitive deterioration with solifenacin versus placebo, when measured at a time point closest to the probable C(max) of solifenacin. Oxybutynin was associated with statistically significant impairments in several measures of cognitive function at a time point corresponding with its probable C(max). In this pilot study, single 10 mg doses of solifenacin did not show any clear propensity to impair cognitive function in a healthy elderly population.

  17. Florfenicol residues in Rainbow Trout after oral dosing in recirculating and flow-through culture systems

    Science.gov (United States)

    Meinertz, Jeffery R.; Hess, Karina R.; Bernady, Jeffry A.; Gaikowski, M. P.; Whitsel, Melissa; Endris, R. G.

    2014-01-01

    Aquaflor is a feed premix for fish containing the broad spectrum antibacterial agent florfenicol (FFC) incorporated at a ratio of 50% (w/w). To enhance the effectiveness of FFC for salmonids infected with certain isolates of Flavobacterium psychrophilum causing coldwater disease, the FFC dose must be increased from the standard 10 mg·kg−1 body weight (BW)·d−1 for 10 consecutive days. A residue depletion study was conducted to determine whether FFC residues remaining in the fillet tissue after treating fish at an increased dose would be safe for human consumption. Groups of Rainbow Trout Oncorhynchus mykiss (total n = 144; weight range, 126–617 g) were treated with FFC at 20 mg·kg−1 BW·d−1 for 10 d in a flow-through system (FTS) and a recirculating aquaculture system (RAS) each with a water temperature of ∼13°C. The two-tank RAS included a nontreated tank containing 77 fish. Fish were taken from each tank (treated tank, n = 16; nontreated tank, n = 8) at 6, 12, 24, 48, 72, 120, 240, 360, and 480 h posttreatment. Florfenicol amine (FFA) concentrations (the FFC marker residue) in skin-on fillets from treated fish were greatest at 12 h posttreatment (11.58 μg/g) in the RAS and were greatest at 6 h posttreatment (11.09 μg/g) in the FTS. The half-lives for FFA in skin-on fillets from the RAS and FTS were 20.3 and 19.7 h, respectively. Assimilation of FFC residues in the fillets of nontreated fish sharing the RAS with FFC-treated fish was minimal. Florfenicol water concentrations peaked in the RAS-treated tank and nontreated tanks at 10 h (453 μg/L) and 11 h (442 μg/L) posttreatment, respectively. Monitoring of nitrite concentrations throughout the study indicated the nitrogen oxidation efficiency of the RAS biofilter was minimally impacted by the FFC treatment.

  18. Prophylactic Oral Dextrose Gel for Newborn Babies at Risk of Neonatal Hypoglycaemia: A Randomised Controlled Dose-Finding Trial (the Pre-hPOD Study).

    Science.gov (United States)

    Hegarty, Joanne Elizabeth; Harding, Jane Elizabeth; Gamble, Gregory David; Crowther, Caroline Anne; Edlin, Richard; Alsweiler, Jane Marie

    2016-10-01

    Neonatal hypoglycaemia is common, affecting up to 15% of newborns, and can cause brain damage. Currently, there are no strategies, beyond early feeding, to prevent neonatal hypoglycaemia. Our aim was to determine a dose of 40% oral dextrose gel that will prevent neonatal hypoglycaemia in newborn babies at risk. We conducted a randomised, double-blind, placebo-controlled dose-finding trial of buccal dextrose gel to prevent neonatal hypoglycaemia at two hospitals in New Zealand. Babies at risk of hypoglycaemia (infant of a mother with diabetes, late preterm delivery, small or large birthweight, or other risk factors) but without indication for admission to a neonatal intensive care unit (NICU) were randomly allocated either to one of four treatment groups: 40% dextrose at one of two doses (0.5 ml/kg = 200 mg/kg, or 1 ml/kg = 400 mg/kg), either once at 1 h of age or followed by three additional doses of dextrose (0.5 ml/kg before feeds in the first 12 h); or to one of four corresponding placebo groups. Treatments were administered by massaging gel into the buccal mucosa. The primary outcome was hypoglycaemia (dextrose gel (relative risk [RR] 0.68; 95% confidence interval [CI] 0.47-0.99, p = 0.04) but was not significantly different between dose groups (p = 0.21). Compared to multiple doses, single doses of gel were better tolerated, quicker to administer, and less messy, but these limitations were not different between dextrose and placebo gel groups. Babies who received any dose of dextrose gel were less likely to develop hypoglycaemia than those who received placebo (RR 0.79; 95% CI 0.64-0.98, p = 0.03; number needed to treat = 10, 95% CI 5-115). Rates of NICU admission were similar (RR 0.64; 95% CI 0.33-1.25, p = 0.19), but admission for hypoglycaemia was less common in babies randomised to dextrose gel (RR 0.46; 95% CI 0.21-1.01, p = 0.05). Rates of breastfeeding were similar in both groups. Adverse effects were uncommon and not different between groups. A

  19. Perbandingan Pengaruh Nifedipin 20 mg per Oral 2 Jam Preoperasi dengan Plasebo terhadap Suhu Inti pada Pasien yang Menjalani Operasi Modified Radical Mastectomy dengan Anestesi Umum

    Directory of Open Access Journals (Sweden)

    Saleh Trisnadi

    2014-08-01

    Full Text Available Strategy of prevention the initial redistribution hypothermia is based on the reduction of the heat gradient between the core and perifer before surgery by administering vasodilators. The purpose of this study was to asses the effect of oral nifedipine 20 mg 2 hours before anesthesia in preventing hypothermia in patients undergoing modified radical mastectomy under general anesthesia and to compare the decreased rate of body temperature oral nifedipine with placebo. The research was done with the prospective method, randomized double-blind controlled study in 30 patients aged 18–60 yrs, American Society of Anesthesiologist (ASA physical status I-II, underwent modified radical mastectomy surgery, were randomly divided into two groups at Dr. Hasan Sadikin General Hospital Bandung during June until August 2012. One group was given oral nifedipine 20 mg 2 hours before general anesthesia and the other group was given placebo. Tymphani temperature was recorded during anesthesia every 10 minutes. Research data was tested statistically by the Mann-Whitney test. The average core temperature in the nifedipine was 36.37 ° C which was higher than the control group 35.61 ° C (p<0.05. It can be concluded that the use of nifedipine can prevent intraoperative hypothermia.

  20. Evaluation of the disintegration properties of commercial famotidine 20 mg orally disintegrating tablets using a simple new test and human sensory test.

    Science.gov (United States)

    Harada, Tsutomu; Narazaki, Ryuichi; Nagira, Shinsuke; Ohwaki, Takayuki; Aoki, Shigeru; Iwamoto, Kiyoshi

    2006-08-01

    The purpose of this study was to demonstrate the usefulness and broad-applicability of a simple disintegration test method for orally disintegrating tablets (ODT). Eight types of commercial famotidine 20 mg orally disintegrating tablets with different physical properties (formulation, manufacturing method, tablet weight, shape, diameter, thickness, etc.), were used. Disintegration times of these tablets were evaluated employing human sensory test, conventional disintegration test, and the new proposed disintegration test. The human sensory test was performed in 5 healthy volunteers. In the conventional disintegration test, the disintegration apparatus described in the Japanese Pharmacopeia (JP 1(st)) was used. Our proposed new test which is characterized by a rotating shaft with a low weight (10, 15 g) and rotation speed (10, 25, 50 rpm) was evaluated using tablets with and without storage under severe conditions (60 degrees C/75%RH for 1 week). The disintegration times of famotidine 20 mg orally disintegrating tablets in human sensory test varied from 9 to 32 s. In contrast, disintegration times in the conventional test were prolonged to over 300 s. Disintegration times in the new proposed test were close to those in human sensory test. Especially, when the new test was conducted with 15 or 10 g weight and 25 rpm, the slope (human sensory test vs. new proposed test) was almost 1. We were able to demonstrate that the new proposed test was useful to estimate the actual human disintegration time.

  1. Effects of recording time and residue on dose-response by LiMgPO4: Tb, B ceramic disc synthesized via improved sintering process

    Science.gov (United States)

    Kong, Xirui; Fu, Zhilong; Que, Huiying; Fan, Yanwei; Chen, Zhaoyang; He, Chengfa

    2018-05-01

    The LiMgPO4: Tb, B ceramic disc is successfully synthesized via improved sintering method which enables the disc sample to have two flat and smooth surfaces. It is worth mentioning that the OSL signal intensity of LiMgPO4: Tb, B disc attenuates much faster than that of commercial Al2O3: C. It costs only 1 s to reduce the intensity to 10%, but the Al2O3:C needs more than 40 s to finish it. Some essential OSL properties related to the dose detection method of this sample also have been systematically investigated. Although the dose-response cure would have better linearity with longer recording time, extended recording time (≥6 s) will not make any contribution to the linearity of the curve. If the bleaching time is more than 35 s, the residue created by previous detection (high dose of 10 Gy) would do almost no influence (with a positive deviation lower than 5.59%) on next lower-dose detection (0.1 Gy). The material would reach its service life when the total-ionizing dose runs up to 30 k Gy. Therefore, the LiMgPO4: Tb, B ceramic material is a potential candidate for real-time dose monitoring with optical fiber telemetering technology.

  2. Effect of rare earth filtration on patient exposure, dose reduction, and image quality in oral panoramic radiology

    International Nuclear Information System (INIS)

    Tyndall, D.A.; Washburn, D.B.

    1987-01-01

    Rare earth intensifying screen material (Gd2O2S:Tb) was added to the standard Al filtration of an oral panoramic x-ray unit, resulting in a beam capable of achieving reductions in patient dose without a loss of image quality. The added rare earth filtration technique resulted in patient dose reductions of 21-56%, depending on anatomic sites, when compared to the conventional Al filtration technique. Films generated from both techniques were measured densitometrically and evaluated by a panel of practicing clinicians. Diagnostically significant differences were minimal. The results indicate that use of rare earth filters in oral panoramic radiography is an effective means of reducing exposures of dental patients to ionizing radiation

  3. Andrographis paniculata: Dissolution investigation and pharmacokinetic studies of four major active diterpenoids after multiple oral dose administration in healthy Thai volunteers.

    Science.gov (United States)

    Pholphana, Nanthanit; Panomvana, Duangchit; Rangkadilok, Nuchanart; Suriyo, Tawit; Puranajoti, Porranee; Ungtrakul, Teerapat; Pongpun, Wanwisa; Thaeopattha, Saichit; Songvut, Phanit; Satayavivad, Jutamaad

    2016-12-24

    Andrographis paniculata is included in 'The National List of Essential Herbal Drugs A.D. 1999' of Thailand as an herbal drug for the treatment of common cold symptoms and non-infectious diarrhea. The therapeutic activities of A. paniculata are attributed to four major active diterpenoids: andrographolide (1), 14-deoxy-11, 12-didehydroandrographolide (2), neoandrographolide (3), and 14-deoxyandrographolide (4). However, the pharmacokinetic studies in humans of this plant were performed after a single oral dose administration and reported the parameters related to be of only 1. This study aims to determine the pharmacokinetic parameters of four major active diterpenoids after multiple oral dose administration of A. paniculata capsules in healthy volunteers. The dissolution testing of these four diterpenoids was also performed. The dissolution testing of four major active diterpenoids was conducted in pH 1.2, pH 4.5, and pH 6.8 for 10-100min. The pharmacokinetic study of these active diterpenoids was designed as an open-label, multiple oral dose administration of A. paniculata capsules in 20 healthy Thai volunteers at 1:1 ratio of female and male. Each volunteer was given four A. paniculata capsules each time which contained 1, 2, 3, and 4 in the quantities of 32.64, 5.40, 3.60, and 3.84mg, respectively, three times a day for three consecutive days. On the fourth day, after the first dose of the day was administered, blood samples were collected at the predefined time points. The validated LC-MS/MS method was used to simultaneously determine the concentrations of these diterpenoids in the human plasma samples. The pharmacokinetic parameters of each active diterpenoid were determined. All four major active diterpenoids have been completely dissolved in the simulated pH of gastrointestinal tract within 60min of dissolution. The dissolution profiles were found to be highest in pH 6.8 and lowest in pH 1.2, especially for 3. In the pharmacokinetic study, although 1 was

  4. Evaluation of Genotoxicity and 28-day Oral Dose Toxicity on Freeze-dried Powder of Tenebrio molitor Larvae (Yellow Mealworm)

    OpenAIRE

    Han, So-Ri; Yun, Eun-Young; Kim, Ji-Young; Hwang, Jae Sam; Jeong, Eun Ju; Moon, Kyoung-Sik

    2014-01-01

    The larval form of Tenebrio molitor (T. molitor) has been eaten in many countries and provides benefits as a new food source of protein for humans. However, no information exists regarding its safety for humans. The objective of the present study was to evaluate the genotoxicity and repeated dose oral toxicity of the freeze-dried powder of T. molitor larvae. The genotoxic potential was evaluated by a standard battery testing: bacterial reverse mutation test, in vitro chromosome aberration tes...

  5. The route of administration (oral vs intravenous) does not influence dose or outcome in Graves' disease and unifocal autonomy

    International Nuclear Information System (INIS)

    Schneider, Peter; Biko, Johannes; Haenscheid, Heribert; Hilliger, Stephan; Koutsampelas, Christos; Kranzfelder, Michael; Ladner, Stephan; Reiners, Christoph

    2005-01-01

    In a prospective randomised study, we investigated the influence of the route of administration of radioiodide on dosimetry and therapy outcome. Fifty-four patients suffering from Graves' disease (GD) and 60 patients with unifocal autonomy (UA) participated in the study and were randomly treated with either orally or intravenously administered radioiodide. Pretherapeutic dosimetry was based on single uptake measurements with a calibrated uptake probe system. The radioiodine kinetics during hospitalisation was assessed by daily bedside uptake measurements. Therapeutic dose was determined by half-life and thyroid uptake at the time of discharge using the same uptake probe as for the radioiodine test. No improvement in accuracy of dosimetry was achieved when radioiodide was administered intravenously. Mean therapeutic doses were identical following intravenous or oral administration. Variation in the achieved dose was slightly higher in the patients receiving oral administration, this being attributable to larger deviations in discrete activities of the capsules administered as compared with the values determined by dosimetry. No differences according to treatment modality were found with regard to therapeutic outcome. Eighty-seven patients attended 6-month follow-up after therapy. In the UA group, successful treatment, defined as a normal or elevated TSH level, was observed in 94% of patients after oral administration and in 80% after intravenous administration; corresponding figures in the GD group were 68% and 65%. The causes of individual differences between targeted and therapeutically achieved doses remain undetermined. Variations in the bioavailability of radioiodide or other parameters affecting thyroid status may be involved, and further investigations are needed to clarify this. (orig.)

  6. Bovine spongiform encephalopathy: the effect of oral exposure dose on attack rate and incubation period in cattle ? an update

    OpenAIRE

    Konold, Timm; Arnold, Mark E; Austin, Anthony R; Cawthraw, Saira; Hawkins, Steve AC; Stack, Michael J; Simmons, Marion M; Sayers, A Robin; Dawson, Michael; Wilesmith, John W; Wells, Gerald AH

    2012-01-01

    Abstract Background To provide information on dose–response and aid in modelling the exposure dynamics of the BSE epidemic in the United Kingdom groups of cattle were exposed orally to a range of different doses of brainstem homogenate of known infectious titre from clinical cases of classical bovine spongiform encephalopathy (BSE). Interim data from this study was published in 2007. This communication documents additional BSE cases, which occurred subsequently, examines possible influence of...

  7. Milk transfer, distribution, and metabolism of a single oral dose of [14CH3S]methamidophos in Sprague Dawley rats

    International Nuclear Information System (INIS)

    Bakry, N.M.; Salama, A.K.; Aly, H.A.; Abou-Donia, M.B.

    1990-01-01

    A single oral dose of 8 mg/kg (8 μci/kg) of [ 14 CH 3 S]methamidophos was administered to the dams right after delivery. Suckling groups were collected at intervals of 1, 3, 6, 12, 24, 36, and 48 hr after dosing. Radiolabeled material was rapidly absorbed and subsequently distributed throughout the body. Generally, the highest concentration of radioactivity were associated with kidneys, liver, lung, small intestine, spleen, stomach, and uterus; the lowest were found in the heart, muscles, skin, diaphragm, brain, spinal cord, and adipose tissues. Total radioactivity in the sucklings reached a maximum value of 1,067 ng methamidophos equivalent (1.89% of applied dose). Methamidophos and its metabolites were analyzed by gas-liquid chromatography/mass spectrometry, thin-layer chromatography and liquid scintillation counting. Methamidophos disappeared biexponentially from the suckling pups. The terminal half-life of methamidophos was 43.5 hr corresponding to a constant rate value of 0.02 hr -1 . The major metabolites in the sucklings were monomethyl phosphoroamidate and monomethyl phosphate

  8. Single Low Dose Primaquine (0.25 mg/kg Does Not Cause Clinically Significant Haemolysis in G6PD Deficient Subjects.

    Directory of Open Access Journals (Sweden)

    Germana Bancone

    Full Text Available Primaquine is the only drug consistently effective against mature gametocytes of Plasmodium falciparum. The transmission blocking dose of primaquine previously recommended was 0.75 mg/kg (adult dose 45 mg but its deployment was limited because of concerns over haemolytic effects in patients with glucose-6-phosphate dehydrogenase (G6PD deficiency. G6PD deficiency is an inherited X-linked enzymatic defect that affects an estimated 400 million people around the world with high frequencies (15-20% in populations living in malarious areas. To reduce transmission in low transmission settings and facilitate elimination of P. falciparum, the World Health Organization now recommends adding a single dose of 0.25 mg/kg (adult dose 15 mg to Artemisinin-based Combination Therapies (ACTs without G6PD testing. Direct evidence of the safety of this low dose is lacking. Adverse events and haemoglobin variations after this treatment were assessed in both G6PD normal and deficient subjects in the context of targeted malaria elimination in a malaria endemic area on the North-Western Myanmar-Thailand border where prevalence of G6PD deficiency (Mahidol variant approximates 15%.The tolerability and safety of primaquine (single dose 0.25 mg base/kg combined with dihydroartemisinin-piperaquine (DHA-PPQ given three times at monthly intervals was assessed in 819 subjects. Haemoglobin concentrations were estimated over the six months preceding the ACT + primaquine rounds of mass drug administration. G6PD deficiency was assessed with a phenotypic test and genotyping was performed in male subjects with deficient phenotypes and in all females. Fractional haemoglobin changes in relation to G6PD phenotype and genotype and primaquine round were assessed using linear mixed-effects models. No adverse events related to primaquine were reported during the trial. Mean fractional haemoglobin changes after each primaquine treatment in G6PD deficient subjects (-5.0%, -4.2% and -4

  9. Ability of Saudi mothers to appropriately and accurately use dosing devices to administer oral liquid medications to their children

    Directory of Open Access Journals (Sweden)

    Almazrou S

    2014-12-01

    Full Text Available Saja Almazrou, Hind Alsahly, Huda Alwattar, Lamya Alturki, Mona Alamri Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia Background: Most liquid medications are packaged with administration devices, which may be used inappropriately or inaccurately, and sometimes are not used at all. Because of the importance of their proper use for children's health, this study was designed to assess Saudi mothers' experiences with measuring cups, syringes, and droppers for oral liquid medications; to compare accuracy of dosing across these devices; and to determine the effects of mothers' education statuses and pharmacist counseling on dosing accuracy. Methods: This was a cross-sectional study in which mothers were observed as they used a set of commonly available dosing devices which are a dosing cup, syringe, and dropper. Interviews were conducted in the outpatient pharmacy waiting area in several tertiary hospitals and primary clinics in Riyadh, Saudi Arabia between March and April 2013. Saudi women who were mothers of children aged 12 years old or younger and who gave their consent were eligible. Caregivers other than mothers and subjects with vision problems or cognitive/physical disabilities were excluded. We gathered demographic information such as age, number of children, and education status. Subjects were asked if they had had counseling on how to use measuring devices and which device they preferred. Then, the mothers were required to demonstrate how to measure 5 mL of paracetamol (acetaminophen syrup using a cup and a syringe and 1 mL of paracetamol syrup using a dropper. Dosing errors were evaluated visually as overdosing, underdosing, or no error (if the dose was accurate. The data were entered into Microsoft Excel and evaluated using Stata 11.1. Logistic regression was employed to determine relationships. Results: The results revealed that 58% of participants measured an accurate dose of paracetamol

  10. The Impact of a One-Dose versus Two-Dose Oral Cholera Vaccine Regimen in Outbreak Settings: A Modeling Study

    Science.gov (United States)

    Azman, Andrew S.; Luquero, Francisco J.; Ciglenecki, Iza; Grais, Rebecca F.; Sack, David A.; Lessler, Justin

    2015-01-01

    Background In 2013, a stockpile of oral cholera vaccine (OCV) was created for use in outbreak response, but vaccine availability remains severely limited. Innovative strategies are needed to maximize the health impact and minimize the logistical barriers to using available vaccine. Here we ask under what conditions the use of one dose rather than the internationally licensed two-dose protocol may do both. Methods and Findings Using mathematical models we determined the minimum relative single-dose efficacy (MRSE) at which single-dose reactive campaigns are expected to be as or more effective than two-dose campaigns with the same amount of vaccine. Average one- and two-dose OCV effectiveness was estimated from published literature and compared to the MRSE. Results were applied to recent outbreaks in Haiti, Zimbabwe, and Guinea using stochastic simulations to illustrate the potential impact of one- and two-dose campaigns. At the start of an epidemic, a single dose must be 35%–56% as efficacious as two doses to avert the same number of cases with a fixed amount of vaccine (i.e., MRSE between 35% and 56%). This threshold decreases as vaccination is delayed. Short-term OCV effectiveness is estimated to be 77% (95% CI 57%–88%) for two doses and 44% (95% CI −27% to 76%) for one dose. This results in a one-dose relative efficacy estimate of 57% (interquartile range 13%–88%), which is above conservative MRSE estimates. Using our best estimates of one- and two-dose efficacy, we projected that a single-dose reactive campaign could have prevented 70,584 (95% prediction interval [PI] 55,943–86,205) cases in Zimbabwe, 78,317 (95% PI 57,435–100,150) in Port-au-Prince, Haiti, and 2,826 (95% PI 2,490–3,170) cases in Conakry, Guinea: 1.1 to 1.2 times as many as a two-dose campaign. While extensive sensitivity analyses were performed, our projections of cases averted in past epidemics are based on severely limited single-dose efficacy data and may not fully capture

  11. Pharmacokinetic evaluation of pamidronate after oral administration: a study on dose proportionality, absolute bioavailability, and effect of repeated administration

    DEFF Research Database (Denmark)

    Hyldstrup, Lars; Flesch, G; Hauffe, S A

    1993-01-01

    30 minutes at constant infusion rate. Repeated peroral doses (75 and 150 mg) were administered to 12 females (aged 51-70 years) for 10 consecutive days. Urinary excretion of pamidronate after peroral and i.v. administration was used for estimation of pamidronate absorption. Renal excretion...... of pamidronate ranged from 0.01% to 0.35% of dose, with mean values of 0.11, 0.16, and 0.18% for 75, 150, and 300 mg, respectively. After i.v. infusion, the renal excretion of pamidronate was 26-53% of the dose, lower than for other bisphosphonates. The absolute bioavailability was 0.31% (range 0.08-0.7%) after...

  12. Uncertainty assessment and comparison of different dose algorithms used to evaluate a two element LiF:Mg,Ti TL personal dosemeter

    International Nuclear Information System (INIS)

    Stadtmann, H.; Hranitzky, F.C.

    2008-01-01

    This paper presents the results of an uncertainty assessment and comparison study of different dose algorithms used for evaluating our routine two element TL whole body dosemeter. Due to the photon energy response of the two different filtered LiF:Mg,Ti detector elements the application of dose algorithms is necessary to assess the relevant photon doses over the rated energy range with an acceptable energy response. Three dose algorithms are designed to calculate the dose for the different dose equivalent quantities, i.e. personal dose equivalent H p (10) and H p (0.07) and photon dose equivalent H x used for personal monitoring before introducing personal dose equivalent. Based on experimental results both for free in air calibration as well as calibration on the ISO water slab phantom (type test data) a detailed uncertainty analysis war performed by means of Monte Carlo simulation techniques. The uncertainty contribution of the individual detector element signals was taken into special consideration. (author)

  13. Randomized, 6-Week, Placebo-Controlled Study of Treatment for Adult Attention-Deficit/Hyperactivity Disorder: Individualized Dosing of Osmotic-Release Oral System (OROS) Methylphenidate With a Goal of Symptom Remission.

    Science.gov (United States)

    Goodman, David W; Starr, H Lynn; Ma, Yi-Wen; Rostain, Anthony L; Ascher, Steve; Armstrong, Robert B

    2017-01-01

    To evaluate the efficacy and safety of individualized dosing within the approved dose range for osmotic-release oral system (OROS) methylphenidate hydrochloride in adults with attention-deficit/hyperactivity disorder (ADHD). A double-blind, 6-week trial was conducted between July 2009 and February 2010 at 35 US sites. Adults with ADHD (DSM-IV diagnostic criteria) and a screening ADHD Investigator Symptom Rating Scale (AISRS) score > 24 were randomly assigned to OROS methylphenidate 18 mg or matching placebo. Treatment dose could be increased at 18 mg increments, up to 72 mg/d, until an optimal dose was achieved. AISRS score changes from baseline to end point (primary outcome) were analyzed using analysis of covariance. At baseline, the intent-to-treat population of 169 OROS methylphenidate and 172 placebo subjects (mean age = 35.8 years) had mean (standard deviation [SD]) AISRS scores of 37.8 (6.94) and 37.0 (7.51), respectively. OROS methylphenidate-treated subjects exhibited a significantly greater mean (SD) AISRS score improvement than placebo subjects (-17.1 [12.44] vs -11.7 [13.30]; P ADHD. OROS methylphenidate treatment with individualized doses titrated to achieve symptom remission demonstrated greater ADHD symptom reduction than placebo treatment. These data support the overall efficacy of OROS methylphenidate treatment in the management of adults with ADHD and provide new possibilities for additional intervention. ClinicalTrials.gov identifier: NCT00937040. © Copyright 2017 Physicians Postgraduate Press, Inc.

  14. Patch test concentrations (doses in mg/cm(2) ) for the 12 non-mix fragrance substances regulated by European legislation

    DEFF Research Database (Denmark)

    Bruze, Magnus; Svedman, Cecilia; Andersen, Klaus Ejner

    2012-01-01

    Background. According to EU legislation, 26 fragrance substance allergens must be labelled on cosmetic products. For 12 of them, the optimal patch test concentration/dose has not been evaluated. Objectives. To establish the optimal patch test doses in mg/cm(2) for the 12 fragrance substances......, it is recommended that half of the maximum patch test dose (mg/cm(2) ) be used for aimed and screening patch testing....... that are not included in fragrance mix I or II in the European baseline patch test series. Materials and Methods. Patch testing with the 12 fragrance substances was performed in a stepwise manner encompassing up to five rounds in at least 100 dermatitis patients for each round. Before patch testing, an individual...

  15. Monte Carlo calculations for doses in organs and tissues to oral radiography; Calculo de Monte Carlo para doses em orgaos e tecidos para radiologia oral

    Energy Technology Data Exchange (ETDEWEB)

    Sampaio, E V.M.

    1986-12-31

    Using the MIRD 5 phantom and Monte Carlo technique, organ doses in patients undergoing external dental examination were calculated taking into account the different x-ray beam geometries and the various possible positions of x-ray source with regard to the head of the patient. It was necessary to introduce in the original computer program a new source description specific for dental examinations. To have a realistic evaluation of organ doses during dental examination it was necessary to introduce a new region in the phantom heat which characterizes the teeth and salivary glands. The attenuation of the x-ray beam by the lead shield of the radiographic film was also introduced in the calculation. (author).

  16. A study investigating the acute dose-response effects of 13 mg and 17 mg Delta 9- tetrahydrocannabinol on cognitive-motor skills, subjective and autonomic measures in regular users of marijuana.

    Science.gov (United States)

    Weinstein, A; Brickner, O; Lerman, H; Greemland, M; Bloch, M; Lester, H; Chisin, R; Sarne, Y; Mechoulam, R; Bar-Hamburger, R; Freedman, N; Even-Sapir, E

    2008-06-01

    Heavy use of marijuana is claimed to damage critical skills related to short-term memory, visual scanning and attention. Motor skills and driving safety may be compromised by the acute effects of marijuana. The aim of this study was to investigate the acute effects of 13 mg and 17 mg Delta 9-tetrahydrocannabinol (THC) on skills important for coordinated movement and driving and on subjective and autonomic measures in regular users of marijuana. Fourteen regular users of marijuana were enrolled. Each subject was tested on two separate days. On each test day, subjects smoked two low-nicotine cigarettes, one with and the other without THC. Seventeen mg THC was included in the cigarette on one test day and 13 mg on the other day. The sequence of cigarette types was unknown to the subject. During smoking, heart rate and blood pressure were monitored, and the subjects performed a virtual reality maze task requiring attention and motor coordination, followed by 3 other cognitive tasks (Wisconsin Card Sorting Test (WCST), a "gambling" task and estimation of time and distance from an approaching car). After smoking a cigarette with 17 mg THC, regular marijuana users hit the walls more often on the virtual maze task than after smoking cigarettes without THC; this effect was not seen in patients after they smoked cigarettes with 13 mg THC. Performance in the WCST was affected with 17 mg THC and to a lesser extent with the use of 13 mg THC. Decision making in the gambling task was affected after smoking cigarettes with 17 mg THC, but not with 13 m THC. Smoking cigarettes with 13 and 17 mg THC increased subjective ratings of pleasure and satisfaction, drug "effect" and drug "high". These findings imply that smoking of 17 mg THC results in impairment of cognitive-motor skills that could be important for coordinated movement and driving, whereas the lower dose of 13 mg THC appears to cause less impairment of such skills in regular users of marijuana.

  17. Prevalence of gastroduodenal ulcers/erosions in patients taking low-dose aspirin with either 15 mg/day of lansoprazole or 40 mg/day of famotidine: The OITA-GF study 2

    Science.gov (United States)

    2013-01-01

    Background The preventive effects of histamine 2 receptor antagonists vs. proton pump inhibitors on low-dose aspirin (LDA)-related gastroduodenal mucosal injury have not been fully investigated. We conducted a cross-sectional study to compare the prevalence of gastroduodenal ulcers or erosions in patients taking LDA with either 40 mg/day of famotidine or 15 mg/day of lansoprazole for at least three months. Methods Of 84 eligible patients, two taking 40 mg/day of famotidine and four taking 15 mg/day of lansoprazole refused to undergo upper gastrointestinal endoscopy. Ultimately, we performed upper gastrointestinal endoscopy in 78 patients taking either 40 mg/day of famotidine (group F, n = 31) or 15 mg/day of lansoprazole (group L, n = 47). The prevalence of gastroduodenal ulcers or erosions and the magnitude of gastric mucosal injury evaluated using modified Lanza scores were compared between the two groups. Results No patients in either group had gastroduodenal ulcers. Gastroduodenal erosions were more prevalent in group F than in group L (48.4% vs. 17.0%, p = 0.005). The modified Lanza scores (mean ± SD) were significantly higher in group F than in group L (0.9 ± 1.3 vs. 0.3 ± 0.7, p = 0.007). A multivariate logistic regression analysis showed that the use of lansoprazole was negatively associated with gastroduodenal erosions. Conclusions This study suggests that 15 mg/day of lansoprazole may be more effective in preventing the development of LDA-related gastroduodenal erosions than 40 mg/day of famotidine. The preventive effects of these two regimens on the development of LDA-related gastroduodenal ulcers require further investigation. PMID:23531145

  18. Prevalence of gastroduodenal ulcers/erosions in patients taking low-dose aspirin with either 15 mg/day of lansoprazole or 40 mg/day of famotidine: the OITA-GF study 2.

    Science.gov (United States)

    Tamura, Akira; Murakami, Kazunari; Kadota, Junichi

    2013-03-26

    The preventive effects of histamine 2 receptor antagonists vs. proton pump inhibitors on low-dose aspirin (LDA)-related gastroduodenal mucosal injury have not been fully investigated. We conducted a cross-sectional study to compare the prevalence of gastroduodenal ulcers or erosions in patients taking LDA with either 40 mg/day of famotidine or 15 mg/day of lansoprazole for at least three months. Of 84 eligible patients, two taking 40 mg/day of famotidine and four taking 15 mg/day of lansoprazole refused to undergo upper gastrointestinal endoscopy. Ultimately, we performed upper gastrointestinal endoscopy in 78 patients taking either 40 mg/day of famotidine (group F, n = 31) or 15 mg/day of lansoprazole (group L, n = 47). The prevalence of gastroduodenal ulcers or erosions and the magnitude of gastric mucosal injury evaluated using modified Lanza scores were compared between the two groups. No patients in either group had gastroduodenal ulcers. Gastroduodenal erosions were more prevalent in group F than in group L (48.4% vs. 17.0%, p = 0.005). The modified Lanza scores (mean ± SD) were significantly higher in group F than in group L (0.9 ± 1.3 vs. 0.3 ± 0.7, p = 0.007). A multivariate logistic regression analysis showed that the use of lansoprazole was negatively associated with gastroduodenal erosions. This study suggests that 15 mg/day of lansoprazole may be more effective in preventing the development of LDA-related gastroduodenal erosions than 40 mg/day of famotidine. The preventive effects of these two regimens on the development of LDA-related gastroduodenal ulcers require further investigation.

  19. Analysis of ethyl acrylate (EA) and acrylic acid (AA) residues from rat tissues following oral ea dosing

    International Nuclear Information System (INIS)

    Udinsky, J.R.; Frederick, C.B.

    1990-01-01

    Gavage dosing of rats with EA at high dose levels (100 or 200 mg/kg) has resulted in tumors at the dosing site, forestomach (FST), but no lesions of the glandular stomach (GST) or other remote tissues. Since previous in vitro studies have demonstrated that EA is very rapidly metabolized to AA and glutathione conjugates, EA and AA residues were analyzed 0-24 hr following gavage dosing of non-fasted F-344/N male rats with [1- 14 C]EA in corn oil at 10, 50, and 200 mg/kg. Analysis of total 14 C indicated that the dose solution was primarily in the FST at ≥5 min after dosing, although 14 C was detected in the GST, duodenum, and small intestine (attributed to distension of the FST and leakage from the FST to the GST). HPLC analysis of the gut contents, gut wall, liver, kidneys, lungs, and blood indicated that EA and AA could only be detected at ≥15 min in the FST and GST contents, and in the FST tissue. AA alone was detected in the GST tissue, duodenum tissue and contents, and small intestine tissue and contents. The minimum level of detection was 0.0005% of the dose. The remaining 14 C was primarily attributed to binding to the gut contents or bioincorporation of AA. The detection of EA and AA residues only in the upper gastrointestinal tract following gavage dosing is consistent with rapid detoxification of EA by hydrolysis and conjugation which prevents toxicity at sites remote form the site of dosing

  20. Effectiveness of one dose of oral cholera vaccine in response to an outbreak: a case-cohort study.

    Science.gov (United States)

    Azman, Andrew S; Parker, Lucy A; Rumunu, John; Tadesse, Fisseha; Grandesso, Francesco; Deng, Lul L; Lino, Richard Laku; Bior, Bior K; Lasuba, Michael; Page, Anne-Laure; Ontweka, Lameck; Llosa, Augusto E; Cohuet, Sandra; Pezzoli, Lorenzo; Sodjinou, Dossou Vincent; Abubakar, Abdinasir; Debes, Amanda K; Mpairwe, Allan M; Wamala, Joseph F; Jamet, Christine; Lessler, Justin; Sack, David A; Quilici, Marie-Laure; Ciglenecki, Iza; Luquero, Francisco J

    2016-11-01

    Oral cholera vaccines represent a new effective tool to fight cholera and are licensed as two-dose regimens with 2-4 weeks between doses. Evidence from previous studies suggests that a single dose of oral cholera vaccine might provide substantial direct protection against cholera. During a cholera outbreak in May, 2015, in Juba, South Sudan, the Ministry of Health, Médecins Sans Frontières, and partners engaged in the first field deployment of a single dose of oral cholera vaccine to enhance the outbreak response. We did a vaccine effectiveness study in conjunction with this large public health intervention. We did a case-cohort study, combining information on the vaccination status and disease outcomes from a random cohort recruited from throughout the city of Juba with that from all the cases detected. Eligible cases were those aged 1 year or older on the first day of the vaccination campaign who sought care for diarrhoea at all three cholera treatment centres and seven rehydration posts throughout Juba. Confirmed cases were suspected cases who tested positive to PCR for Vibrio cholerae O1. We estimated the short-term protection (direct and indirect) conferred by one dose of cholera vaccine (Shanchol, Shantha Biotechnics, Hyderabad, India). Between Aug 9, 2015, and Sept 29, 2015, we enrolled 87 individuals with suspected cholera, and an 898-person cohort from throughout Juba. Of the 87 individuals with suspected cholera, 34 were classified as cholera positive, 52 as cholera negative, and one had indeterminate results. Of the 858 cohort members who completed a follow-up visit, none developed clinical cholera during follow-up. The unadjusted single-dose vaccine effectiveness was 80·2% (95% CI 61·5-100·0) and after adjusting for potential confounders was 87·3% (70·2-100·0). One dose of Shanchol was effective in preventing medically attended cholera in this study. These results support the use of a single-dose strategy in outbreaks in similar epidemiological

  1. Oral calcitonin

    Directory of Open Access Journals (Sweden)

    Hamdy RC

    2012-09-01

    Full Text Available Ronald C Hamdy,1,2 Dane N Daley11Osteoporosis Center, College of Medicine, East Tennessee State University, 2Veterans Affairs Medical Center, Johnson City, TN, USAAbstract: Calcitonin is a hormone secreted by the C-cells of the thyroid gland in response to elevations of the plasma calcium level. It reduces bone resorption by inhibiting mature active osteoclasts and increases renal calcium excretion. It is used in the management of postmenopausal osteoporosis, Paget's disease of bone, and malignancy-associated hypercalcemia. Synthetic and recombinant calcitonin preparations are available; both have similar pharmacokinetic and pharmacodynamic profiles. As calcitonin is a peptide, the traditional method of administration has been parenteral or intranasal. This hinders its clinical use: adherence with therapy is notoriously low, and withdrawal from clinical trials has been problematic. An oral formulation would be more attractive, practical, and convenient to patients. In addition to its effect on active osteoclasts and renal tubules, calcitonin has an analgesic action, possibly mediated through β-endorphins and the central modulation of pain perception. It also exerts a protective action on cartilage and may be useful in the management of osteoarthritis and possibly rheumatoid arthritis. Oral formulations of calcitonin have been developed using different techniques. The most studied involves drug-delivery carriers such as Eligen® 8-(N-2hydroxy-5-chloro-benzoyl-amino-caprylic acid (5-CNAC (Emisphere Technologies, Cedar Knolls, NJ. Several factors affect the bioavailability and efficacy of orally administered calcitonin, including amount of water used to take the tablet, time of day the tablet is taken, and proximity to intake of a meal. Preliminary results looked promising. Unfortunately, in two Phase III studies, oral calcitonin (0.8 mg with 200 mg 5-CNAC, once a day for postmenopausal osteoporosis and twice a day for osteoarthritis failed to

  2. Conscious Sedation Efficacy of 0.3 and 0.5 mg/kg Oral Midazolam for Three to Six Year-Old Uncooperative Children Undergoing Dental Treatment: A Clinical Trial

    Directory of Open Access Journals (Sweden)

    Masoud Fallahinejad Ghajari

    2016-10-01

    Full Text Available Objectives: Midazolam with variable dosages has been used to induce sedation in pediatric dentistry. The aim of this study was to compare the efficacy of two dosages of oral midazolam for conscious sedation of children undergoing dental treatment.Materials and Methods: In this randomized crossover double blind clinical trial, 20 healthy children (ASA I aged three to six years with negative or definitely negative Frankl behavioral rating scale were evaluated. Half of the children received 0.5mg/kg oral midazolam plus 1mg/kg hydroxyzine (A orally in the first session and 0.3mg/kg oral midazolam plus 1mg/kg hydroxyzine (B in the next session. The other half received the drugs on a reverse order. Sedation degree by Houpt sedation rating scale, heart rate and level of SpO2 were assessed at the beginning and after 15 and 30 minutes. The data were analyzed using SPSS 19 and Wilcoxon Signed Rank and McNemar’s tests.Results: The results showed that although administration of 0.5mg/kg oral midazolam was slightly superior to 0.3mg/kg oral midazolam in terms of sedation efficacy, the differences were not significant (P>0.05. The difference in treatment success was not significant either (P>0.05. Heart rate, oxygen saturation (SpO2 and respiratory rate were within the normal range and did not show a significant change (P>0.05.Conclusions: The overall success rate of the two drug combinations namely 0.5mg/kg oral midazolam plus hydroxyzine and 0.3mg/kg oral midazolam plus hydroxyzine was not significantly different for management of pediatric patients.Keywords: Conscious Sedation; Pediatric Dentistry; Midazolam; Hydroxyzine

  3. Pulsed-dosing with oral sodium phenylbutyrate increases hemoglobin F in a patient with sickle cell anemia.

    Science.gov (United States)

    Hines, Patrick; Dover, George J; Resar, Linda M S

    2008-02-01

    Increasing hemoglobin F (HbF) appears to be beneficial for patients with sickle cell anemia. We previously demonstrated that daily, oral sodium phenylbutyrate (OSPB) induces HbF synthesis in pediatric and adult patients with hemoglobin SS (HbSS). The high doses and need for daily therapy, however, have limited its use. Here, we report a patient treated with pulsed-dosing of OSPB for over 3 years. This patient developed a modest, but sustained elevation in HbF over the course of therapy without side effects. Although larger studies are needed, this case demonstrates that pulsed-dosing with OSPB enhances HbF synthesis. (c) 2007 Wiley-Liss, Inc.

  4. Superantigen-Induced Cytokine Release from Whole-Blood Cell Culture as a Functional Measure of Drug Efficacy after Oral Dosing in Nonhuman Primates

    National Research Council Canada - National Science Library

    Krakauer, Teresa; Stephens, Julie; Buckley, Marilyn; Tate, Mallory

    2007-01-01

    ...) closely resemble humans. We examined the ex vivo cytokine response of superantigen-stimulated whole-blood cells as a first step to therapeutic efficacy testing for bacterial superantigen-induced shock in NHP after oral dosing of pentoxifylline...

  5. Relative bioavailability of single doses of prolonged-release tacrolimus administered as a suspension, orally or via a nasogastric tube, compared with intact capsules: a phase 1 study in healthy participants.

    Science.gov (United States)

    Undre, Nasrullah; Dickinson, James

    2017-04-04

    Tacrolimus, an immunosuppressant widely used in solid organ transplantation, is available as a prolonged-release capsule for once-daily oral administration. In the immediate postsurgical period, if patients cannot take intact capsules orally, tacrolimus therapy is often initiated as a suspension of the capsule contents, delivered orally or via a nasogastric tube. This study evaluated the relative bioavailability of prolonged-release tacrolimus suspension versus intact capsules in healthy participants. A phase 1, open-label, single-dose, cross-over study. A single clinical research unit. In total, 20 male participants, 18-55 years old, entered and completed the study. All participants received nasogastric administration of tacrolimus 10 mg suspension in treatment period 1, with randomisation to oral administration of suspension or intact capsules in periods 2 and 3. Blood concentration-time profile over 144 hours was used to estimate pharmacokinetic parameters. Primary end point: relative bioavailability of prolonged-release intact capsule versus oral or nasogastric administration of prolonged-release tacrolimus suspension (area under the concentration-time curve (AUC) from time 0 to infinity post-tacrolimus dose (AUC 0-∞ ); AUC measured until the last quantifiable concentration (AUC 0-tz ); maximum observed concentration (C max ); time to C max (T max )). Tolerability was assessed throughout the study. Relative bioavailability of prolonged-release tacrolimus suspension administered orally was similar to intact capsules, with a ratio of least-square means for AUC 0-tz and AUC 0-∞ of 1.05 (90% CI 0.96 to 1.14). Bioavailability was lower with suspension administered via a nasogastric tube versus intact capsules (17%; ratio 0.83; CI 0.76 to 0.92). C max was higher for oral and nasogastric suspension (30% and 28%, respectively), and median T max was shorter (difference 1.0 and 1.5 hours postdose, respectively) versus intact capsules (2.0 hours). Single 10 mg

  6. Effervescent N-Acetylcysteine Tablets versus Oral Solution N-Acetylcysteine in Fasting Healthy Adults: An Open-Label, Randomized, Single-Dose, Crossover, Relative Bioavailability Study

    Directory of Open Access Journals (Sweden)

    Spencer C. Greene, MD, FACEP, FACMT

    2016-01-01

    Conclusions: Data from this study of a single dose of 11 g oral NAC demonstrated that effervescent NAC tablets and oral solution NAC met the regulatory criteria for bioequivalence in fasting healthy adult subjects. Effervescent NAC tablets appear to be a more palatable alternative for treatment of acetaminophen overdose. ClinicalTrials.gov identifier: NCT02723669.

  7. Brief oral cryotherapy for the prevention of high-dose melphalan-induced stomatitis in allogeneic hematopoietic stem cell transplant recipients.

    Science.gov (United States)

    Mori, Takehiko; Yamazaki, Rie; Aisa, Yoshinobu; Nakazato, Tomonori; Kudo, Masumi; Yashima, Tomoko; Kondo, Sakiko; Ikeda, Yasuo; Okamoto, Shinichiro

    2006-04-01

    We previously reported the efficacy of oral cryotherapy for the prevention of high-dose melphalan-induced stomatitis. The purpose of this study was to evaluate whether the further shortening of the duration of oral cryotherapy could minimize its side effects while sparing its efficacy. Seventeen consecutive recipients of allogeneic hematopoieic stem cell transplant conditioned with high-dose melphalan in combination with fludarabine alone or with fludarabine and additional radiation were enrolled in the study. The severity of stomatitis was graded according to the National Cancer Institute-Common Toxicity Criteria. Patients were kept on oral cryotherapy shortly before, during, and for additional 30 min after the completion of melphalan administration (60-min oral cryotherapy). Patients who were also enrolled in our previous study received the same type of oral cryotherapy but for additional 90 min after the completion of melphalan administration (120-min oral cryotherapy), and they served as controls. Only 2 (11.8%) of 17 patients receiving 60-min oral cryotherapy and 2 (11.1%) of 18 patients receiving 120-min oral cryotherapy developed grade 2 or 3 stomatitis, respectively. The difference between groups was not statistically significant (P = 0.677). The incidence of unpleasant symptoms such as chills and nausea during oral cryotherapy decreased significantly with 60-min oral cryotherapy, as compared with that associated with 120-min oral cryotherapy (P cryotherapy is as effective as 120-min oral cryotherapy at preventing high-dose melphalan-induced stomatitis, and shorter treatment might have contributed to relieve patient discomfort during oral cryotherapy.

  8. Calibration of Mg2SiO4(Tb) thermoluminescent dosimeters for use in determining diagnostic X-ray doses to Adult Health Study participants

    International Nuclear Information System (INIS)

    Kato, Kazuo; Antoku, Shigetoshi; Sawada, Shozo; Russell, W.J.

    1989-11-01

    Characteristics of Mg 2 SiO 4 (Tb) thermoluminescent dosimeters (TLD) were ascertained preparatory to measuring dose from diagnostic X-ray examinations received by Adult Health Study participants. These detectors are small, relatively sensitive to low-dose X rays, and are appropriate for precise dosimetry. Extensive calibration is necessary for precisely determining doses according to their thermoluminescent intensities. Their sensitivities were investigated, by dose according to X-ray tube voltage, and by exposure direction, to obtain directional dependence. Dosimeter sensitivity lessened due to the fading effect and diminution of the planchet. However, these adverse effects can be avoided by storing the dosimeters at least 1.5 hours and by using fresh silver-plated planchets. Thus, the TLDs, for which sensitivities were determined in this study, will be useful in subsequent diagnostic X-ray dosimetry. (author)

  9. Effects of a MATE protein inhibitor, pyrimethamine, on the renal elimination of metformin at oral microdose and at therapeutic dose in healthy subjects.

    Science.gov (United States)

    Kusuhara, H; Ito, S; Kumagai, Y; Jiang, M; Shiroshita, T; Moriyama, Y; Inoue, K; Yuasa, H; Sugiyama, Y

    2011-06-01

    A microdose study of metformin was conducted to investigate the predictability of drug-drug interactions at the therapeutic dose (ThD). Healthy subjects received a microdose (100 µg) or ThD (250 mg) of metformin orally, with or without a potent and competitive multidrug and toxin extrusion (MATE) inhibitor, pyrimethamine (50 mg, p.o.), in a crossover fashion. Pyrimethamine significantly reduced the renal clearance of metformin by 23 and 35% at the microdose and ThD, respectively. At ThD, but not at microdose, it caused significant increases in the maximum concentration (C(max)) and area under the plasma concentration-time curve (AUC) of metformin (142 and 139% of control values, respectively). Human canalicular membrane vesicles showed pyrimethamine-inhibitable metformin uptake. Pyrimethamine did not affect plasma lactate/pyruvate after ThD of metformin but significantly reduced the renal clearance of creatinine, thereby causing elevation of plasma creatinine level. This microdose study quantitatively predicted a drug-drug interaction involving the renal clearance of metformin at ThD by pyrimethamine. Pyrimethamine is a useful in vivo inhibitor of MATE proteins.

  10. Pre-Altitude Serum Ferritin Levels and Daily Oral Iron Supplement Dose Mediate Iron Parameter and Hemoglobin Mass Responses to Altitude Exposure.

    Directory of Open Access Journals (Sweden)

    Andrew D Govus

    Full Text Available To investigate the influence of daily oral iron supplementation on changes in hemoglobin mass (Hbmass and iron parameters after 2-4 weeks of moderate altitude exposure.Hematological data collected from 178 athletes (98 males, 80 females exposed to moderate altitude (1,350-3,000 m were analysed using linear regression to determine how altitude exposure combined with oral iron supplementation influenced Hbmass, total iron incorporation (TII and blood iron parameters [ferritin and transferrin saturation (TSAT].Altitude exposure (mean ± s: 21 ± 3 days increased Hbmass by 1.1% [-0.4, 2.6], 3.3% [1.7, 4.8], and 4.0% [2.0, 6.1] from pre-altitude levels in athletes who ingested nil, 105 mg and 210 mg respectively, of oral iron supplement daily. Serum ferritin levels decreased by -33.2% [-46.9, -15.9] and 13.8% [-32.2, 9.7] from pre-altitude levels in athletes who supplemented with nil and 105 mg of oral iron supplement daily, but increased by 36.8% [1.3, 84.8] in athletes supplemented with 210 mg of oral iron daily. Finally, athletes who ingested either 105 mg or 210 mg of oral iron supplement daily had a greater TII compared with non-supplemented athletes (0 versus 105 mg: effect size (d = -1.88 [-2.56, -1.17]; 0 versus 210 mg: effect size (d = -2.87 [-3.88, -1.66].Oral iron supplementation during 2-4 weeks of moderate altitude exposure may enhance Hbmass production and assist the maintenance of iron balance in some athletes with low pre-altitude iron stores.

  11. A Phase II feasibility study of oral etoposide given concurrently with radiotherapy followed by dose intensive adjuvant chemotherapy for children with newly diagnosed high-risk medulloblastoma (protocol POG 9631): A report from the Children's Oncology Group.

    Science.gov (United States)

    Esbenshade, Adam J; Kocak, Mehmet; Hershon, Linda; Rousseau, Pierre; Decarie, Jean-Claude; Shaw, Susan; Burger, Peter; Friedman, Henry S; Gajjar, Amar; Moghrabi, Albert

    2017-06-01

    Children with high-risk medulloblastoma historically have had a poor prognosis. The Children's Oncology Group completed a Phase II study using oral etoposide given with radiotherapy followed by intensive chemotherapy. Patients enrolled in the study had high-risk disease defined as ≥1.5 cm 2 of residual disease postsurgery or definite evidence of central nervous metastasis. All patients underwent surgery followed by radiotherapy. During radiation, the patients received oral etoposide (21 days on, 7 off) at an initial dose of 50 mg/m 2 per day (treatment 1), which was reduced to 35 mg/m 2 per day (treatment 2) due to toxicity. After radiotherapy, the patients received chemotherapy with three cycles of cisplatin and oral etoposide, followed by eight courses of cyclophosphamide and vincristine. Between November 1998 and October 2002, 53 patients were accrued; 15 received treatment 1 and 38 treatment 2. Forty-seven patients (89%) were eligible. Response to radiation was excellent, with 19 (40.4%) showing complete response, 24 (51.1%) partial response, and four (8.5%) no recorded response. The overall 2- and 5-year progression-free survival (PFS) was 76.6 ± 6% and 70.2 ± 7%, respectively. The 2- and 5-year overall survival (OS) was 80.9 ± 6% and 76.6 ± 6%, respectively. Clinical response postradiation and PFS/OS were not significantly different between the treatment groups. There was a trend toward a difference in 5-year PFS between those without and with metastatic disease (P = 0.072). Oral etoposide was tolerable at 35 mg/m 2 (21 days on and 7 days off) when given during full-dose irradiation in patients with high-risk medulloblastoma with encouraging survival data. © 2016 Wiley Periodicals, Inc.

  12. Method of thermoluminescent measurement of radiation doses from micrograys up to a megagray with a single LiF: Mg,Cu,P detector

    International Nuclear Information System (INIS)

    Obryk, B.; Bilski, P.; Olko, P.

    2011-01-01

    On the basis of the newly discovered behaviour of LiF:Mg,Cu,P detectors at high and ultra-high doses, a new method of thermoluminescence (TL) measurement of radiation doses ranging from micrograys up to a megagray, has been recently developed at the Inst. of Nuclear Physics (IFJ). The method is based on the relationship between the TL signal, integrated in the given temperature range and dose. It is quantified by a parameter called the 'ultra-high temperature ratio'. It has been demonstrated that this new method can measure radiation doses in the range of about 1 μGy to 1 MGy, using a single LiF:Mg,Cu,P detector. This method was recently successfully blindly tested for 10 MeV electrons up to doses of 200 kGy. It can be used for dosimetry in high-energy accelerators, especially in the Large Hadron Collider at CERN, and has great potential for accident dosimetry in particular. (authors)

  13. Patch test concentrations (doses in mg/cm2 ) for the 12 non-mix fragrance substances regulated by European legislation.

    Science.gov (United States)

    Bruze, Magnus; Svedman, Cecilia; Andersen, Klaus Ejner; Bruynzeel, Derk; Goossens, An; Johansen, Jeanne Duus; Matura, Mihaly; Orton, David; Vigan, Martine

    2012-03-01

    According to EU legislation, 26 fragrance substance allergens must be labelled on cosmetic products. For 12 of them, the optimal patch test concentration/dose has not been evaluated. To establish the optimal patch test doses in mg/cm2 for the 12 fragrance substances that are not included in fragrance mix I or II in the European baseline patch test series. Patch testing with the 12 fragrance substances was performed in a stepwise manner encompassing up to five rounds in at least 100 dermatitis patients for each round. Before patch testing, an individual maximum concentration/dose was determined for each fragrance substance. The predetermined maximum patch test concentrations/doses could be tested for all 12 fragrance substances, with no observable adverse reactions being noted. For each fragrance substance investigated, it is recommended that half of the maximum patch test dose (mg/cm2) be used for aimed and screening patch testing. © 2012 John Wiley & Sons A/S.

  14. Successful pregnancy following low-dose hCG administration in addition to hMG in a patient with hypothalamic amenorrhea due to weight loss.

    Science.gov (United States)

    Tsutsumi, Ryo; Fujimoto, Akihisa; Osuga, Yutaka; Harada, Miyuki; Takemura, Yuri; Koizumi, Minako; Yano, Tetsu; Taketani, Yuji

    2012-06-01

    We describe successful ovulation induction with low-dose hCG administration in addition to hMG in a patient with refractory hypothalamic amenorrhea. A 24-year-old woman with weight loss-related amenorrhea underwent ovulation induction and intracytoplasmic sperm injection (ICSI). Administration of exogenous gonadotropins was ineffective in ovulation induction. Supplementation with low-dose hCG in order to increase luteinizing hormone (LH) activity in the late follicular phase produced late folliculogenesis and steroidogenesis, and ovulation was then successfully induced. This report reacknowledges the critical role that LH plays cooperatively with follicle-stimulating hormone in both folliculogenesis and steroidogenesis.

  15. Comparative trial of two intravenous doses of granisetron (1 versus 3 mg) in the prevention of chemotherapy-induced acute emesis: a double-blind, randomized, non-inferiority trial.

    Science.gov (United States)

    Tsuji, Daiki; Kim, Yong-Il; Taku, Keisei; Nakagaki, Shigeru; Ikematsu, Yoshito; Tsubota, Hiromi; Maeda, Masato; Hashimoto, Naoya; Kimura, Masayuki; Daimon, Takashi

    2012-05-01

    A single 3 mg or 40 μg/kg intravenous dose of granisetron combined with dexamethasone is routinely used in several countries, although the antiemetic guidelines have recommended granisetron at the dose of 1 mg or 10 μg/kg. A randomized, multicenter trial was conducted to determine the optimal intravenous granisetron dose, 1 or 3 mg, in cancer patients receiving emetogenic chemotherapy. We enrolled 365 patients and randomly assigned them to receive intravenous granisetron 3 mg (3-mg group) or 1 mg (1-mg group), combined with dexamethasone at an adequate dose fixed as per the emetic risk category. The primary end point was the proportion of patients with a complete response during the first 24 h after chemotherapy. The study demonstrated that 1 mg of granisetron was not inferior in effect to 3 mg. For the primary end point, 359 patients were evaluable according to the modified intention-to-treat (ITT) analysis. Complete protection was achieved in the modified ITT population, 90.6% and 88.8% for the 3- and 1-mg groups, respectively (p granisetron is not inferior to 3 mg when both doses are combined with dexamethasone. Therefore, 1-mg dose of intravenous granisetron should be the recommended prophylactic regimen for the prevention of acute emesis.

  16. Effects of Oral Administration of Nicotine on Organ Weight, Serum ...

    African Journals Online (AJOL)

    This study investigated the effects of oral administration of nicotine on body and reproductive organ weight, serum testosterone level and testicular histology in adult male rats. Forty male rats divided into five groups and treated for a period of 30 days with 0.5mg/kg (low dose) and 1.0mg/kg (high dose) body weight of ...

  17. Premenstrual dysphoric disorder symptom cluster improvement by cycle with the combined oral contraceptive ethinylestradiol 20 mcg plus drospirenone 3 mg administered in a 24/4 regimen.

    Science.gov (United States)

    Marr, Joachim; Niknian, Minoo; Shulman, Lee P; Lynen, Richard

    2011-07-01

    A combined oral contraceptive comprising ethinylestradiol (EE) 20 mcg/drospirenone 3 mg in a 24/4 regimen has been clinically shown to alleviate the symptoms associated with premenstrual dysphoric disorder (PMDD). However, previous studies did not report data according to cycle-by-cycle improvement. This was a subanalysis of a Phase III, double-blind, multicenter, United States-based study. Women with confirmed PMDD were randomized to EE 20 mcg/drospirenone 3 mg 24/4 or placebo for three treatment cycles. Ten of the 21 emotional and physical items on the Daily Record of Severity of Problems scale were grouped to define three symptom clusters: (a) negative emotions, (b) food cravings and (c) water retention-related symptoms. The change from baseline at each treatment cycle was compared between groups using a weighted analysis of covariance model. The full analysis set comprised 449 women. Daily Record of Severity of Problems scores for each symptom cluster were significantly reduced from baseline with both EE 20 mcg/drospirenone 3 mg 24/4 and placebo (pemotions, food cravings and water retention-related symptoms to a significantly greater extent than placebo during all three cycles of treatment. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. Efficacy and persistence of low-dose mirabegron (25 mg) in patients with overactive bladder: analysis in a real-world urological practice.

    Science.gov (United States)

    Shen, Yuan Chi; Wang, Hung Jen; Chuang, Yao Chi

    2018-06-07

    Mirabegron is a relatively new drug to treat overactive bladder (OAB). The therapeutic doses are between 25 and 100 mg in clinical trials. We aimed to evaluate the efficacy and persistence of low-dose mirabegron (25 mg) in patients with OAB in daily urological practice. The study was a retrospective consecutive cohort of 177 OAB patients (101 male and 76 female) treated with 25 mg of mirabegron mg since January 2016 to November 2016. The therapeutic outcomes were assessed at baseline, 4, 12, and 24 weeks. Mirabegron usage was associated with a statistically significant decrease in Overactive Bladder Symptom Score, Urgency Severity Score, urge urinary incontinence, International Prostate Symptom Score (both storage and voiding symptom) at 4-week follow-up, and the therapeutic effects were further improved at 12- and 24-week follow-up. Among them, 118 patients (66.7%) and 84 patients (47.5%) were maintained on mirabegron therapy for more than 3 and 6 months, respectively. However, 29 patients (16%) had poor response with drug discontinuation within 3 months and 8 patients (4.5%) stopped medication due to adverse effects. The overall side effect was 10.2%, and the most common side effect was elevated blood pressure (2.8%) and increased post-void residual (2.8%). Between male and female patients, there was no statistical difference of symptom improvement and drug persistence rate. Low-dose mirabegron (25 mg) improves clinical outcomes in two-thirds of OAB patients with good safety profile and high persistence in daily urological practice. The therapeutic effect is similar between the genders.

  19. Phase I-II study of everolimus and low-dose oral cyclophosphamide in patients with metastatic renal cell cancer

    International Nuclear Information System (INIS)

    Huijts, Charlotte M; Santegoets, Saskia J; Eertwegh, Alfons J van den; Pijpers, Laura S; Haanen, John B; Gruijl, Tanja D de; Verheul, Henk M; Vliet, Hans J van der

    2011-01-01

    For patients with metastatic renal cell cancer (mRCC) who progressed on vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor therapy, the orally administered mammalian target of rapamycin (mTOR) inhibitor everolimus has been shown to prolong progression free survival. Intriguingly, inhibition of mTOR also promotes expansion of immunosuppressive regulatory T cells (Tregs) that can inhibit anti-tumor immune responses in a clinically relevant way in various tumor types including RCC. This study intends to investigate whether the antitumor efficacy of everolimus can be increased by preventing the detrimental everolimus induced expansion of Tregs using a metronomic schedule of cyclophosphamide. This phase I-II trial is a national multi-center study of different doses and schedules of low-dose oral cyclophosphamide in combination with a fixed dose of everolimus in patients with mRCC not amenable to or progressive after a VEGF-receptor tyrosine kinase inhibitor containing treatment regimen. In the phase I part of the study the optimal Treg-depleting dose and schedule of metronomic oral cyclophosphamide when given in combination with everolimus will be determined. In the phase II part of the study we will evaluate whether the percentage of patients progression free at 4 months of everolimus treatment can be increased from 50% to 70% by adding metronomic cyclophosphamide (in the dose and schedule determined in the phase I part). In addition to efficacy, we will perform extensive immune monitoring with a focus on the number, phenotype and function of Tregs, evaluate the safety and feasibility of the combination of everolimus and cyclophosphamide, perform monitoring of selected angiogenesis parameters and analyze everolimus and cyclophosphamide drug levels. This phase I-II study is designed to determine whether metronomic cyclophosphamide can be used to counter the mTOR inhibitor everolimus induced Treg expansion in patients with metastatic renal cell

  20. Phase I-II study of everolimus and low-dose oral cyclophosphamide in patients with metastatic renal cell cancer

    Directory of Open Access Journals (Sweden)

    Huijts Charlotte M

    2011-11-01

    Full Text Available Abstract Background For patients with metastatic renal cell cancer (mRCC who progressed on vascular endothelial growth factor (VEGF receptor tyrosine kinase inhibitor therapy, the orally administered mammalian target of rapamycin (mTOR inhibitor everolimus has been shown to prolong progression free survival. Intriguingly, inhibition of mTOR also promotes expansion of immunosuppressive regulatory T cells (Tregs that can inhibit anti-tumor immune responses in a clinically relevant way in various tumor types including RCC. This study intends to investigate whether the antitumor efficacy of everolimus can be increased by preventing the detrimental everolimus induced expansion of Tregs using a metronomic schedule of cyclophosphamide. Methods/design This phase I-II trial is a national multi-center study of different doses and schedules of low-dose oral cyclophosphamide in combination with a fixed dose of everolimus in patients with mRCC not amenable to or progressive after a VEGF-receptor tyrosine kinase inhibitor containing treatment regimen. In the phase I part of the study the optimal Treg-depleting dose and schedule of metronomic oral cyclophosphamide when given in combination with everolimus will be determined. In the phase II part of the study we will evaluate whether the percentage of patients progression free at 4 months of everolimus treatment can be increased from 50% to 70% by adding metronomic cyclophosphamide (in the dose and schedule determined in the phase I part. In addition to efficacy, we will perform extensive immune monitoring with a focus on the number, phenotype and function of Tregs, evaluate the safety and feasibility of the combination of everolimus and cyclophosphamide, perform monitoring of selected angiogenesis parameters and analyze everolimus and cyclophosphamide drug levels. Discussion This phase I-II study is designed to determine whether metronomic cyclophosphamide can be used to counter the mTOR inhibitor everolimus

  1. Effects of oral bexarotene (targretin) on the minimal erythema dose for broadspectrum UVB light.

    NARCIS (Netherlands)

    Smit, J.V.; Jong, E.M.G.J. de; Kerkhof, P.C.M. van de

    2003-01-01

    Photo(chemo)therapy and oral retinoid therapy for psoriasis or cutaneous T-cell lymphoma are frequently combined to obtain an enhanced therapeutic effect with lower safety risks. Bexarotene, a new RXR-selective retinoid (rexinoid), has been developed for the treatment of cutaneous T-cell lymphoma

  2. Phase I dose-escalation study to examine the safety and tolerability of LY2603618, a checkpoint 1 kinase inhibitor, administered 1 day after pemetrexed 500 mg/m(2) every 21 days in patients with cancer.

    Science.gov (United States)

    Weiss, Glen J; Donehower, Ross C; Iyengar, Tara; Ramanathan, Ramesh K; Lewandowski, Karen; Westin, Eric; Hurt, Karla; Hynes, Scott M; Anthony, Stephen P; McKane, Scott

    2013-02-01

    This phase I study aims at assessing the safety and tolerability of LY2603618, a selective inhibitor of Checkpoint Kinase 1, in combination with pemetrexed and determining the maximum tolerable dose and the pharmacokinetic parameters. This was an open-label, multicenter, dose-escalation study in patients with advanced solid tumors. Increasing doses of LY2603618 (40-195 mg/m(2)) were combined with 500 mg/m(2) of pemetrexed. LY2603618 was administered on Days 1 and 9 and pemetrexed on Day 8 in a 28-day cycle. For all subsequent 21-day cycles, pemetrexed was administered on Day 1 and LY2603618 on Day 2. Antitumor activity was evaluated as per Response Evaluation Criteria in Solid Tumors 1.0. A total of 31 patients were enrolled into six cohorts (three at 40 mg/m(2) over 4.5-hour infusion, 1-hour infusion in subsequent cohorts: three each at 40 mg/m(2), 70 mg/m(2), and 195 mg/m(2); 13 at 105 mg/m(2); six at 150 mg/m(2)). Four patients experienced a dose-limiting toxicity: diarrhea (105 mg/m(2)); reversible infusion-related reaction (150 mg/m(2)); thrombocytopenia (195 mg/m(2)); and fatigue (195 mg/m(2)). The maximum tolerated dose was defined as 150 mg/m(2). The pharmacokinetic data demonstrated that the exposure of LY2603618 increased in a dose-dependent manner, displayed a suitable half-life for maintaining required human exposures while minimizing the intra- and inter-cycle accumulation, and was unaffected by the pemetrexed administration. The pharmacokinetic-defined biologically efficacious dose was achieved at doses ≥105 mg/m(2). LY2603618 administered approximately 24 h after pemetrexed showed acceptable safety and pharmacokinetic profiles.

  3. Macroscopic, pathologic and immunologic investigations of ten patients with carcinoma of oral cavity treated by a single large dose irradiation

    International Nuclear Information System (INIS)

    Mikuriya, Shuichi; Saito, Tsutomu; Konoeda, Koichi; Igarashi, Seishi; Hirohashi, Hitoshi

    1979-01-01

    The immunosuppressive effect of radiation has been emphasized. Although the irradiated cancer cells die gradually during the treatment, it is understood that they keep cancer specific antigenecity in that process. Another words, we assume that the immunologic capacity participates in the dying process of cancer cells by radiotherapy. We have been preferring to treat carcinoma by a single large dose irradiation method because this method does not impair the patient's immunologic capacity. On this time, we treated ten patients with carcinoma of oral cavity by this method and could obtain favorable results. 1) Ten patients with carcinoma of oral cavity classified in T1N0M0-T3N0M0 were irradiated by 4 - 10 MeV betatron electron. In seven patients, 2,500 - 3,000 rads were given at once and other three patients were irradiated with fractionated dose of 1,000 rads three times within two weeks (total 3,000 rads per two weeks). 2) Effects of a single large dose irradiation were remarkable and almost all cancer cells in these patients disappeared both macroscopically and pathologically. 3) According to the results of cellular immunity tests, numbers of peripheral lymphocytes, absolute numbers of fractionated T and B cells, and blastoid formation rate of lymphocytes stimulated by PHA in vitro were all increased and values obtained by four kinds of skin tests were also elevated after the radiations. These results indicate that the single large dose irradiation for these patients does not impair the immunologic capacity of the patients. (author)

  4. Pharmacokinetic comparison of sustained- and immediate-release oral formulations of cilostazol in healthy Korean subjects: a randomized, open-label, 3-part, sequential, 2-period, crossover, single-dose, food-effect, and multiple-dose study.

    Science.gov (United States)

    Lee, Donghwan; Lim, Lay Ahyoung; Jang, Seong Bok; Lee, Yoon Jung; Chung, Jae Yong; Choi, Jong Rak; Kim, Kiyoon; Park, Jin Woo; Yoon, Hosang; Lee, Jaeyong; Park, Min Soo; Park, Kyungsoo

    2011-12-01

    A sustained-release (SR) formulation of cilostazol was recently developed in Korea and was expected to yield a lower C(max) and a similar AUC to the immediate-release (IR) formulation. The goal of the present study was to compare the pharmacokinetic profiles of a newly developed SR formulation and an IR formulation of cilostazol after single- and multiple-dose administration and to evaluate the influence of food in healthy Korean subjects. This study was developed as part of a product development project at the request of the Korean regulatory agency. This was a randomized, 3-part, sequential, open-label, 2-period crossover study. Each part consisted of different subjects between the ages of 19 and 55 years. In part 1, each subject received a single dose of SR (200 mg × 1 tablet, once daily) and IR (100 mg × 2 tablets, BID) formulations of cilostazol orally 7 days apart in a fasted state. In part 2, each subject received a single dose of the SR (200 mg × 1 tablet, once daily) formulation of cilostazol 7 days apart in a fasted and a fed state. In part 3, each subject received multiple doses of the 2 formulations for 8 consecutive days 21 days apart. Blood samples were taken for 72 hours after the dose. Cilostazol pharmacokinetics were determined for both the parent drug and its metabolites (OPC-13015 and OPC-13213). Adverse events were evaluated through interviews and physical examinations. Among the 92 enrolled subjects (66 men, 26 women; part 1, n = 26; part 2, n = 26; part 3, n = 40), 87 completed the study. In part 1, all the primary pharmacokinetic parameters satisfied the criterion for assumed bioequivalence both in cilostazol and its metabolites, yielding 90% CI ratios of 0.9624 to 1.2323, 0.8873 to 1.1208, and 0.8919 to 1.1283 for C(max) and 0.8370 to 1.0134, 0.8204 to 0.9807, and 0.8134 to 0.9699 for AUC(0-last) of cilostazol, OPC-13015, and OPC-13213, respectively. In part 2, food intake increased C(max) and AUC significantly (P food and 23 with a high

  5. Oral Toxicity of Agro-Fungicides: Tilt (Propiconazole), Bayleton ...

    African Journals Online (AJOL)

    Methods: Twelve Nubian goats were used in these experiments; they were grouped into three groups (and one control group) and dosed orally with two fungicides [Propiconazole (100mg/kg/day), Triadimefon (100mg/kg/day)] and their mixture (50:50 mg/kg/day). Animals were closely observed for clinical signs and behavior ...

  6. Oral pyridoxine can substitute for intravenous pyridoxine in managing patients with severe poisoning with isoniazid and rifampicin fixed dose combination tablets: a case report.

    Science.gov (United States)

    Dilrukshi, M D S A; Ratnayake, C A P; Gnanathasan, C A

    2017-08-08

    Fixed drug combination of isoniazid and rifampicin is a rare cause of poisoning even in endemic countries for tuberculosis infection. Severe poisoning can cause severe morbidity and mortality if not treated promptly. Though intravenous pyridoxine is the preferred antidote for severe standard isoniazid poisoning it is not freely available even in best of care centers. We describe a case of severe poisoning with fixed drug combination of isoniazid and rifampicin successfully managed with oral pyridoxine at national hospital of Sri Lanka. A 22 year old, Sri Lankan female presented to a local hospital 1 h after self-ingestion of 28 tablets of fixed drug combination of isoniazid and rifampicin which contained 4.2 g of standard isoniazid and 7.2 g of rifampicin. One and half hours after ingestion she developed generalized tonic-clonic seizure with loss of consciousness. She was given intravenous diazepam 5 mg immediately and transferred to national hospital of Sri Lanka, for further care. Upon arrival to tertiary care hospital in 3.5 h of poisoning she had persistent vomiting, dizziness and headache. On examination, she was drowsy but arousable, orange-red discoloration of the body was noted even with the dark skin complexion. She also had orange-red colour urine and vomitus. Pulse rate was 104 beats/min, blood pressure 130/80 mmHg, respiratory rate was 20 breaths/min. The arterial blood gas analysis revealed compensated metabolic acidosis and mildly elevated lactic acid level. Considering the clinical presentation with neurological toxicity and the large amount of isoniazid dose ingested, crushed oral tablets of pyridoxine 4.2 g (equal to standard isoniazid dose ingested) administered immediately via a nasogastric tube since intravenous preparation was not available in the hospital. Simultaneously forced diuresis using intravenous 0.9% saline was commenced in order to enhance excretion of toxic metabolites via kidneys. She had no recurrence of seizures but had

  7. Relationship between the ability of oral streptococci to interact with platelet glycoprotein Ibalpha and with the salivary low-molecular-weight mucin, MG2.

    Science.gov (United States)

    Plummer, Christopher; Douglas, Charles William Ian

    2006-12-01

    The oral streptococci Streptococcus sanguinis, Streptococcus gordonii and Streptococcus oralis are common aetiological agents of infective endocarditis, and their ability to adhere to and induce the aggregation of platelets is thought to be a virulence trait. The platelet glycoprotein GPIbalpha has been implicated as the adhesion receptor for S. sanguinis and S. gordonii, but it is not known if this is the case for S. oralis and other species. The aim of this study was to determine the GPIbalpha-interactive capability of a range of oral streptococci and to determine the relationship between this capability and their ability to interact with the salivary constituents that they would encounter in their normal habitat. All platelet-adhesive S. sanguinis strains and most S. gordonii strains adhered in a GPIbalpha-dependent manner, but strains of S. oralis, Streptococcus cristatus, Streptococcus parasanguinis and Streptococcus mitis had no direct affinity for platelets. Those strains that were able to bind GPIbalpha also bound to the low-molecular-weight submandibular salivary mucin, MG2, and this interaction was sialic acid-dependent. The data suggest that S. sanguinis and S. gordonii may be efficient colonizers of platelet vegetations because of their adaptation to recognize sialylated salivary mucins. In contrast, S. oralis does not interact with platelets and so is likely to colonize vegetations through an as yet unidentified mechanism.

  8. Human kinetics of orally and intravenously administered low-dose 1,2-(13)C-dichloroacetate.

    Science.gov (United States)

    Jia, Minghong; Coats, Bonnie; Chadha, Monisha; Frentzen, Barbara; Perez-Rodriguez, Javier; Chadik, Paul A; Yost, Richard A; Henderson, George N; Stacpoole, Peter W

    2006-12-01

    Dichloroacetate (DCA) is a putative environmental hazard, owing to its ubiquitous presence in the biosphere and its association with animal and human toxicity. We sought to determine the kinetics of environmentally relevant concentrations of 1,2-(13)C-DCA administered to healthy adults. Subjects received an oral or intravenous dose of 2.5 microg/kg of 1,2-(13)C-DCA. Plasma and urine concentrations of 1,2-(13)C-DCA were measured by a modified gas chromatography-tandem mass spectrometry method. 1,2-(13)C-DCA kinetics was determined by modeling using WinNonlin 4.1 software. Plasma concentrations of 1,2-(13)C-DCA peaked 10 minutes and 30 minutes after intravenous or oral administration, respectively. Plasma kinetic parameters varied as a function of dose and duration. Very little unchanged 1,2-(13)C-DCA was excreted in urine. Trace amounts of DCA alter its own kinetics after short-term exposure. These findings have important implications for interpreting the impact of this xenobiotic on human health.

  9. 40 CFR 799.9305 - TSCA Repeated dose 28-day oral toxicity study in rodents.

    Science.gov (United States)

    2010-07-01

    ... considered necessary. The limit test applies except when human exposure indicates the need for a higher dose..., stereotypies (e.g., excessive grooming, repetitive circling) or bizarre behaviour (e.g., self-mutilation...

  10. Indications for suboptimal low-dose direct oral anticoagulants for non-valvular atrial fibrillation patients

    Directory of Open Access Journals (Sweden)

    Masahiko Umei, MD

    2017-10-01

    Conclusions: With good adherence, the clinical course associated with DOACs is comparatively good. In the future, suboptimal low-dose DOAC therapy may serve as an appropriate choice for some patients with a high risk of stroke and bleeding.

  11. Radiation dose calculations for orally administered radio-pharmaceuticals in upper gastrointestinal disease

    International Nuclear Information System (INIS)

    Wu, R.K.; Malmud, L.S.; Knight, L.C.; Siegel, J.A.; Stern, H.; Zelac, R.

    1983-01-01

    Radiation burden estimates for upper gastrointestinal function studies employing the following orally administered radiopharmaceuticals are reported. Technetium 99m sulfur colloid (Tc-99m-SC) in water, Indium-111-DTPA in water, Tc-99m-DTPA in water, Indium-113m DTPA in water, Tc-99m Ovalbumin, Tc-99m sulfur colloid in a cooked egg, Tc-99m sulfur colloid in vivo labeled chicken liver, and Indium-111 colloid in vivo labeled chicken liver. Orally administered radiopharmaceuticals for upper gastrointestinal studies afford clinician and investigator valuable clinical and physiologic information not previously obtainable using other techniques. The radiation burden to the patient from single or sequential studies is acceptable in comparison to fluoroscopy which results in approximately 5000 millirem per minute of exposure. The variety of preparations listed above should make these types of studies available in any routinely equipped nuclear medicine radiopharmacy laboratory

  12. Pharmacokinetic Evaluation of a Single Intramuscular High Dose versus an Oral Long-Term Supplementation of Cholecalciferol.

    Directory of Open Access Journals (Sweden)

    Katharina Wylon

    Full Text Available Vitamin D deficiency is frequent during the winter and occurs throughout the year in the elderly or patients suffering from autoimmune diseases. The objective of this study was to evaluate the pharmacokinetic properties of oral supplementation versus a single intramuscular injection of cholecalciferol in healthy individuals.Up to 8,000 I.U. oral cholecalciferol was administered daily for 84 days in a 4 week dose-escalation setting to vitamin D deficient individuals. In another cohort, a single intramuscular injection of 100,000 I.U. cholecalciferol was given. In both cohorts, individuals without vitamin D intake served as the comparison group. 25-hydroxyvitamin D (25(OHD concentrations were measured in all individuals at defined time points throughout the studies.The mean 25(OHD serum concentration increased significantly after oral cholecalciferol intake compared to the control group (day 28: 83.4 nmol/l and 42.5 nmol/l; day 56: 127.4 nmol/l and 37.3 nmol/l; day 84: 159.7 nmol/l and 30.0 nmol/l. In individuals receiving 100,000 I.U. cholecalciferol intramuscular, the mean 25(OHD serum concentration peaked after 4 weeks measuring 70.9 nmol/l compared to 32.7 nmol/l in the placebo group (p = 0.002. The increase of 25(OHD serum concentrations after 28 days was comparable between both routes of administration (p = 0.264.Oral and intramuscular cholecalciferol supplementation effectively increased serum 25(OHD concentrations.

  13. Mass vaccination with a two-dose oral cholera vaccine in a long-standing refugee camp, Thailand.

    Science.gov (United States)

    Phares, Christina R; Date, Kashmira; Travers, Philippe; Déglise, Carole; Wongjindanon, Nuttapong; Ortega, Luis; Bhuket, Ponchanok Rattanadilok Na

    2016-01-02

    During 2005-2012, surveillance in Maela refugee camp, Thailand, identified four cholera outbreaks, with rates up to 10.7 cases per 1000 refugees. In 2013, the Thailand Ministry of Public Health sponsored a two-dose oral cholera vaccine (OCV) campaign for the approximately 46,000 refugees living in Maela. We enumerated the target population (refugees living in Maela who are ≥1 year old and not pregnant) in a census three months before the campaign and issued barcoded OCV cards to each individual. We conducted the campaign using a fixed-post strategy during two eight-day rounds plus one two-day round for persons who had missed their second dose and recorded vaccine status for each individual. To identify factors associated with no vaccination (versus at least one dose) and those associated with adverse events following immunization (AEFI), we used separate marginal log-binomial regression models with robust variance estimates to account for household clustering. A total of 63,057 OCV doses were administered to a target population of 43,485 refugees. An estimated 35,399 (81%) refugees received at least one dose and 27,658 (64%) received two doses. A total of 993 additional doses (1.5%) were wasted including 297 that were spat out. Only 0.05% of refugees, mostly children, could not be vaccinated due to repeated spitting. Characteristics associated with no vaccination (versus at least one dose) included age ≥15 years (versus 1-14 years), Karen ethnicity (versus any other ethnicity) and, only among adults 15-64 years old, male sex. Passive surveillance identified 84 refugees who experienced 108 AEFI including three serious but coincidental events. The most frequent AEFI were nausea (49%), dizziness (38%), and fever (30%). Overall, AEFI were more prevalent among young children and older adults. Our results suggest that mass vaccination in refugee camps with a two-dose OCV is readily achievable and AEFI are few. Published by Elsevier Ltd.

  14. Comparison of a single-dose vectored thermal pulsation procedure with a 3-month course of daily oral doxycycline for moderate-to-severe meibomian gland dysfunction

    Directory of Open Access Journals (Sweden)

    Hagen KB

    2018-01-01

    Full Text Available Kerry B Hagen,1 Raman Bedi,2 Caroline A Blackie,3 Kellie J Christenson-Akagi1 1EyeHealth Northwest, Portland, OR, USA; 2Iris Advanced Eye Centre, Chandigarh, India; 3TearScience, Inc., Morrisville, NC, USA Purpose: The aim of this study was to compare the efficacy of a single bilateral 12-minute vectored thermal pulsation (VTP procedure versus daily oral doxycycline for 3 months for moderate-to-severe meibomian gland dysfunction (MGD.Methods: This prospective, randomized, parallel-group, single-masked study included 28 subjects who received either a single-dose VTP or 3 months of doxycycline treatment. At baseline and 3 months post treatment, all subjects were evaluated for the following: dry eye symptoms with a standard dry eye questionnaire (the Standard Patient Evaluation for Eye Dryness [SPEED], meibomian gland (MG function by counting the number of glands yielding liquid secretion with the MG evaluator (MGE, tear breakup time (TBUT and corneal and conjunctival staining.Results: In the VTP group, at 3 months, there was a significant improvement in MG function (4.00±1.47 to 7.73±5.53, SPEED score (11.00±3.30 to 5.42±2.15, TBUT (6.26±2.01 to 8.44±1.81, corneal staining (0.38±0.50 to 0.12±0.33 and conjunctival staining (1.69±1.93 to 0.62±0.85. In the doxycycline group, there was a significant improvement in MG function (4.63±1.41 to 10.63±5.91, SPEED score (13.42±4.17 to 9.42±5.47 and conjunctival staining (2.38±1.88 to 1.13±1.51, but the improvement in TBUT (6.90±2.56 to 7.59±2.03 and corneal staining (0.21±0.41 to 0.13±0.34 was not statistically significant (p=0.262 and p=0.414, respectively. At 3 months, SPEED score was significantly better in the VTP group (p<0.05; other parameters were comparable between the two groups.Conclusion: A single 12-minute bilateral VTP procedure was significantly more effective than the 3-month daily course of oral doxycycline at improving the dry eye symptoms secondary to MGD. A single

  15. Follicular development in a 7-day versus 4-day hormone-free interval with an oral contraceptive containing 20 mcg ethinyl estradiol and 1 mg norethindrone acetate.

    Science.gov (United States)

    Rible, Radhika D; Taylor, DeShawn; Wilson, Melissa L; Stanczyk, Frank Z; Mishell, Daniel R

    2009-03-01

    Combined oral contraceptive (COC) formulations with 20 mcg ethinyl estradiol (EE) have a greater incidence of ovarian hormone production and follicular development, which can be managed by shortening the number of hormone-free days per COC cycle. This study evaluates differences in follicular development during a 7-day versus 4-day hormone-free interval in a COC regimen with 20 mcg EE and 1 mg norethindrone acetate. Forty-one healthy women were randomized in an open-label fashion to this formulation in either a 24/4 or a 21/7 day regimen for three cycles. Estradiol, progesterone, follicle-stimulating hormone, luteinizing hormone and inhibin B were measured daily from Cycle 2, Day 21 to Cycle 3, Day 3 and on Day 7 of Cycle 3. Follicular diameter and Hoogland score were calculated on Cycle 2, Days 21, 24 and 28 and Cycle 3, Days 3 and 7. Sixty-six percent of subjects in the 21/7 group and 70% of the subjects in the 24/4 group developed a follicle greater than 10 mm diameter. Ovarian steroid hormone levels, Hoogland scores and bleeding patterns were not statistically significant between the groups. In contrast to prior studies, this analysis suggests no difference in follicle development or bleeding patterns among women receiving a 21/7 or 24/4 regimen of a 20-mcg EE/1-mg norethindrone acetate COC.

  16. Clinical Parameters following Multiple Oral Dose Administration of a Standardized Andrographis paniculata Capsule in Healthy Thai Subjects.

    Science.gov (United States)

    Suriyo, Tawit; Pholphana, Nanthanit; Ungtrakul, Teerapat; Rangkadilok, Nuchanart; Panomvana, Duangchit; Thiantanawat, Apinya; Pongpun, Wanwisa; Satayavivad, Jutamaad

    2017-06-01

    Andrographis paniculata has been widely used in Scandinavian and Asian counties for the treatment of the common cold, fever, and noninfectious diarrhea. The present study was carried out to investigate the physiological effects of short-term multiple dose administration of a standardized A. paniculata capsule used for treatment of the common cold and uncomplicated upper respiratory tract infections, including blood pressure, electrocardiogram, blood chemistry, hematological profiles, urinalysis, and blood coagulation in healthy Thai subjects. Twenty healthy subjects (10 males and 10 females) received 12 capsules per day orally of 4.2 g of a standardized A. paniculata crude powder (4 capsules of 1.4 g of A. paniculata , 3 times per day, 8 h intervals) for 3 consecutive days. The results showed that all of the measured clinical parameters were found to be within normal ranges for a healthy person. However, modulation of some parameters was observed after the third day of treatment, for example, inductions of white blood cells and absolute neutrophil count in the blood, a reduction of plasma alkaline phosphatase, and an induction of urine pH. A rapid and transient reduction in blood pressure was observed at 30 min after capsule administration, resulting in a significant reduction of mean systolic blood pressure. There were no serious adverse events observed in the subjects during the treatment period. In conclusion, this study suggests that multiple oral dosing of A. paniculata at the normal therapeutic dose for the common cold and uncomplicated upper respiratory tract infections modulates various clinical parameters within normal ranges for a healthy person. Georg Thieme Verlag KG Stuttgart · New York.

  17. Variabilidade clínica na determinação da dose tóxica oral em intoxicação experimental por fluoroacetato de sódio em gatos

    Directory of Open Access Journals (Sweden)

    Rita de Cássia Collicchio-Zuanaze

    2006-02-01

    Full Text Available O fluoroacetato de sódio (FAS ou composto 1080 é um potente rodenticida utilizado no controle de roedores e predadores mamíferos. Sua utilização está proibida por lei em diversos países devido à sua alta toxicidade, mas no Brasil há evidências do uso ilegal e sem critérios causando intoxicações, principalmente em crianças e animais domésticos. O FAS age por meio do seu metabólito tóxico, o fluorocitrato, no bloqueio do ciclo de Krebs com conseqënte diminuição da produção de energia do organismo, provocando principalmente manifestações clínicas neurológicas e cardíacas. No presente estudo compararam quatro doses orais tóxicas do fluoroacetato de sódio, descritas em gatos, na literatura, observando-se o aparecimento dos sinais clínicos predominantes da intoxicação, as diferenças entre as doses quanto a variabilidade clínica em relação ao período de latência para o aparecimento dos sinais clínicos e sua respectiva intensidade. A dose oral tóxica que melhor caracterizou o quadro clínico da intoxicação por FAS em gatos, sem causar a letalidade aguda, foi de 0,45mg/kg. As diferenças entre as manifestações clínicas foram dose-dependentes e em ordem crescente de intensidade, caracterizando-se como sinais leves (dose 1: 0,3mg/kg, leves a moderados (dose 2: 0,4mg/kg, moderados a graves (dose 3: 0,45mg/kg e graves (dose 4: 0,5mg/kg. Houve também variabilidade clínica individual entre animais intoxicados com a mesma dosagem do tóxico.

  18. The repair of low dose UV light-induced damage to human skin DNA in condition of trace amount Mg 2+

    Science.gov (United States)

    Gao, Fang; Guo, Zhouyi; Zheng, Changchun; Wang, Rui; Liu, Zhiming; Meng, Pei; Zhai, Juan

    2008-12-01

    Ultraviolet light-induced damage to human skin DNA was widely investigated. The primary mechanism of this damage contributed to form cyclobutane pyrimidine dimmers (CPDs). Although the distribution of UV light-induced CPDs within a defined sequence is similar, the damage in cellular environment which shields the nuclear DNA was higher than that in organism in apparent dose. So we use low UVB light as main study agent. Low dose UV-irradiated HDF-a cells (Human Dermal Fibroblasts-adult cells) which is weaker than epidermic cells were cultured with DMEM at different trace amount of Mg2+ (0mmol/L , 0.1mmol/L , 0.2mmol/L, 0.4mmol/L, 0.8mmol/L, 1.2mmol/L) free-serum DMEM and the repair of DNA strands injured were observed. Treat these cells with DNA strand breaks detection, photoproducts detection and the repair of photoproducts detection. Then quantitate the role of trace amount Mg2+ in repair of UV light-induced damage to human skin. The experiment results indicated that epidermic cells have capability of resistance to UV-radiation at a certain extent. And Mg2+ can regulate the UV-induced damage repair and relative vitality. It can offer a rationale and experiment data to relieve UV light-induced skin disease.

  19. Evaluation of sphingolipids in Wistar rats treated to prolonged and single oral doses of fumonisin b₁.

    Science.gov (United States)

    Direito, Glória M; Almeida, Adriana P; Aquino, Simone; dos Reis, Tatiana Alves; Pozzi, Claudia Rodrigues; Corrêa, Benedito

    2009-01-01

    The objective of the present study was to evaluate sphingolipid levels (sphingosine-So and sphinganine-Sa) and to compare the Sa/So ratio in liver, serum and urine of Wistar rats after prolonged administration (21 days) of fumonisin B(1) (FB(1)). In parallel, the kinetics of sphingolipid elimination in urine was studied in animals receiving a single dose of FB(1). Prolonged exposure to FB(1) caused an increase in Sa levels in urine, serum and liver. The most marked effect on sphingolipid biosynthesis was observed in animals treated with the highest dose of FB(1). Animals receiving a single dose of FB(1) presented variations in Sa and So levels and in the Sa/So ratio.

  20. Basal and meal-stimulated ghrelin, PYY, CCK levels and satiety in lean women with polycystic ovary syndrome: effect of low-dose oral contraceptive.

    Science.gov (United States)

    Arusoglu, Gulcan; Koksal, Gulden; Cinar, Nese; Tapan, Serkan; Aksoy, Duygu Yazgan; Yildiz, Bulent O

    2013-11-01

    Ghrelin is an orexigenic peptide that stimulates food intake, whereas peptide YY (PYY) and cholecystokinin (CCK) are anorexigenic gut hormones. Patients with polycystic ovary syndrome (PCOS) appear to have alterations in appetite regulation. We aimed to determine whether fasting or meal-stimulated ghrelin, PYY, CCK, and satiety responses are different between lean PCOS patients and healthy women. We also aimed to assess the potential effect of oral contraceptive use on these hormones and satiety response. We conducted a prospective observational study in a university practice. Eighteen lean PCOS patients and 18 healthy control women matched for age and body mass index underwent measurements of circulating ghrelin, PYY, CCK, and satiety index (SI) before and after a standardized mixed meal at 0, 15, 30, 45, 60, 90, 120, and 180 minutes. For PCOS patients who were treated with ethinyl estradiol 30 μg/drospirenone 3 mg for 3 months, measurements were repeated. We measured ghrelin, PYY, and CCK levels and SI. At baseline, fasting ghrelin, PYY, CCK, and SI values in PCOS patients were not different from controls. Meal-stimulated PYY, CCK, and SI were also not different between the groups, whereas PCOS patients had significantly lower meal-stimulated ghrelin levels compared to controls (P = .04). Ghrelin, PYY, CCK, and SI did not show a significant change after treatment with ethinyl estradiol/drospirenone for 3 months. Basal and stimulated hunger and satiety hormones in lean PCOS patients are not different from lean healthy women, except for a lower meal-stimulated ghrelin response. Short-term use of a low-dose oral contraceptive does not have an effect on appetite regulation of PCOS.

  1. Low dose oral desmopressin for nocturnal polyuria in patients with benign prostatic hyperplasia: a double-blind, placebo controlled, randomized study.

    Science.gov (United States)

    Wang, Chung-Jing; Lin, Yu-Nan; Huang, Shi-Wei; Chang, Chien-Hsing

    2011-01-01

    We evaluated the long-term efficacy and safety of low dose oral desmopressin in elderly patients with benign prostatic hyperplasia with more than nocturnal voids and nocturnal polyuria more than 30% of total daily urine volume. Eligible patients with benign prostatic hyperplasia older than 65 years with nocturia, nocturnal polyuria and International Prostate Symptom Score 14 or greater were included in the study. All patients received placebo or 0.1 mg desmopressin orally at bedtime. Patients were required to visit the outpatient clinic from the first visit, and after 1, 3, 6 and 12 months of treatment. Patients maintained flow volume charts and used diaries to record voiding data throughout the study. During followup urinalysis, urine sodium, urine osmolality, serum electrolytes, prostate specific antigen, International Prostate Symptom Score, quality of life, transrectal ultrasonography of prostate, uroflowmetry and post-void residual urine volume were performed at each visit. A total of 115 patients were enrolled in the study and randomized as 58 in the placebo group and 57 in the desmopressin group. Desmopressin significantly decreased nocturnal urine output and the number of nocturia episodes, and prolonged the first sleep period (p polyuria in the lower urinary tract symptoms of patients with benign prostatic hyperplasia. Long-term desmopressin therapy gradually decreases serum sodium and it might induce hyponatremia even in patients without initial hyponatremia. For long-term desmopressin administration serum sodium should be assessed carefully, at least at 1 week after treatment. Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  2. Review of once-monthly oral ibandronate and the use thereof

    African Journals Online (AJOL)

    The MOBILE study was a prospective, randomised, phase lll, non- inferiority study that compared the efficacy and safety of three once-monthly oral ibandronate doses (50+50 mg monthly, given on 2 consecutive days; 100 mg monthly; 150 mg monthly) with. 2.5 mg daily ibandronate, which has previously been shown.

  3. Every-other-day Dosing of Oral Viscous Budesonide Is not Effective in the Management of Eosinophlic Esophagitis.

    Science.gov (United States)

    Rubinstein, Eitan; Hait, Elizabeth E; Mitchell, Paul D; Lee, John J

    2018-03-01

    Eosinophilic esophagitis (EoE) is a clinicopathologic disorder characterized histologically by esophageal eosinophilia. Oral viscous budesonide (OVB) is an effective treatment with remission rates reported between 55% and 87%; however, topical corticosteroids are associated with increased risk of candidal esophagitis and adrenal suppression. Attempts to decrease the daily dose of topical steroids have resulted in disease relapse. The objective of this study was to determine whether or not reducing the frequency of OVB administration would be effective in controlling esophageal eosinophilia in children and adolescents. Data were obtained by retrospective chart review of patients at Boston Children's Hospital diagnosed with EoE, based on endoscopic findings of >15 eosinophils per high power field (eos/HPF) on esophageal biopsies while on acid blockade. Patients with histologic evidence of response (<15 eos/HPF) while on daily OVB had been offered the option of maintenance therapy based on a Monday-Wednesday-Friday (MWF) dosing regimen. Changes in peak esophageal eosinophil counts over time were examined. Eight male patients ages 5 to 18 years attained clinical response while receiving daily OVB and were subsequently maintained on a MWF OVB dosing regimen for 3 to 7 months. All 8 patients showed an increase in peak esophageal eosinophils, with 7 of 8 (88%) experiencing disease relapse. In fact, the distribution of peak esophageal eosinophils after MWF dosing was not statistically different from peak levels at diagnosis (P = 0.95). An MWF dosing regimen of OVB was not effective at maintaining histologic response in children and adolescents with EoE. Larger prospective studies are warranted to confirm these results.

  4. An open-label, randomized, controlled, multicenter study exploring two treatment strategies of rivaroxaban and a dose-adjusted oral vitamin K antagonist treatment strategy in subjects with atrial fibrillation who undergo percutaneous coronary intervention (PIONEER AF-PCI).

    Science.gov (United States)

    Gibson, C Michael; Mehran, Roxana; Bode, Christoph; Halperin, Johnathan; Verheugt, Freek; Wildgoose, Peter; van Eickels, Martin; Lip, Gregory Y H; Cohen, Marc; Husted, Steen; Peterson, Eric; Fox, Keith

    2015-04-01

    Guidelines recommendations regarding anticoagulant therapy after percutaneous coronary intervention (PCI) among patients with atrial fibrillation (AF) rely on retrospective, nonrandomized observational data. Currently, patients are treated with triple-therapy (dual antiplatelet therapy [DAPT] + oral anticoagulation therapy), but neither the duration of DAPT nor the level of anticoagulation has been studied in a randomized fashion. Recent studies also suggest dual pathway therapy with clopidogrel plus oral anticoagulation therapy may be superior, and other studies suggest that novel oral anticoagulants such as rivaroxaban may further improve patient outcomes. PIONEER AF-PCI (ClinicalTrials.gov NCT01830543) is an exploratory, open-label, randomized, multicenter clinical study assessing the safety of 2 rivaroxaban treatment strategies and 1 vitamin K antagonist (VKA) treatment strategy in subjects who have paroxysmal, persistent, or permanent nonvalvular AF and have undergone PCI with stent placement. Approximately 2,100 subjects will be randomized in a 1:1:1 ratio to receive either rivaroxaban 15 mg once daily plus clopidogrel 75 mg daily for 12 months (a WOEST trial-like strategy), or rivaroxaban 2.5 mg twice daily (with stratification to a prespecified duration of DAPT 1, 6, or 12 months, an ATLAS trial-like strategy), or dose-adjusted VKA once daily (with stratification to a prespecified duration of DAPT 1, 6, or 12 months, traditional triple therapy). All patients will be followed up for 12 months for the primary composite end point of Thrombolysis in Myocardial Infarction major bleeding, bleeding requiring medical attention, and minor bleeding (collectively, clinically significant bleeding). The PIONEER AF-PCI study is the first randomized comparison of VKA vs novel oral anticoagulant therapy in patients with NVAF receiving antiplatelet therapy after PCI to assess the relative risks of bleeding complications. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Radiation dose estimates for oral agents used in upper gastrointestinal disease

    International Nuclear Information System (INIS)

    Siegel, J.A.; Wu, R.K.; Knight, L.C.; Zelac, R.E.; Stern, H.S.; Malmud, L.S.

    1983-01-01

    Radiation dosimetry was calculated for a number of orally administered radiopharmaceuticals used for study of upper gastrointestinal function. These include: Tc-99m sulfur colloid in water, in a cooked egg, and in chicken liver labeled in vivo; In-111 DTPA; Tc-99m DTPA; In-113m DTPA; Tc-99m ovalbumin in cooked egg; and In-111 colloid in chicken liver labeled in vivo. Radiation burdens to the stomach, small intestine, upper and lower large intestine, ovaries, testes, and total body are calculated for each preparation

  6. Repeated Dose 28-Days Oral Toxicity Study of Carica papaya L. Leaf Extract in Sprague Dawley Rats

    Directory of Open Access Journals (Sweden)

    Hussin Muhammad

    2012-04-01

    Full Text Available Carica papaya L. leaves have been used in ethnomedicine for the treatment of fevers and cancers. Despite its benefits, very few studies on their potential toxicity have been described. The aim of the present study was to characterize the chemical composition of the leaf extract from ‘Sekaki’ C. papaya cultivar by UPLC-TripleTOF-ESI-MS and to investigate the sub-acute oral toxicity in Sprague Dawley rats at doses of 0.01, 0.14 and 2 g/kg by examining the general behavior, clinical signs, hematological parameters, serum biochemistry and histopathology changes. A total of twelve compounds consisting of one piperidine alkaloid, two organic acids, six malic acid derivatives, and four flavonol glycosides were characterized or tentatively identified in the C. papaya leaf extract. In the sub-acute study, the C. papaya extract did not cause mortality nor were treatment-related changes in body weight, food intake, water level, and hematological parameters observed between treatment and control groups. Some biochemical parameters such as the total protein, HDL-cholesterol, AST, ALT and ALP were elevated in a non-dose dependent manner. Histopathological examination of all organs including liver did not reveal morphological alteration. Other parameters showed non-significant differences between treatment and control groups. The present results suggest that C. papaya leaf extract at a dose up to fourteen times the levels employed in practical use in traditional medicine in Malaysia could be considered safe as a medicinal agent.

  7. Alternative methods for the median lethal dose (LD(50)) test: the up-and-down procedure for acute oral toxicity.

    Science.gov (United States)

    Rispin, Amy; Farrar, David; Margosches, Elizabeth; Gupta, Kailash; Stitzel, Katherine; Carr, Gregory; Greene, Michael; Meyer, William; McCall, Deborah

    2002-01-01

    The authors have developed an improved version of the up-and-down procedure (UDP) as one of the replacements for the traditional acute oral toxicity test formerly used by the Organisation for Economic Co-operation and Development member nations to characterize industrial chemicals, pesticides, and their mixtures. This method improves the performance of acute testing for applications that use the median lethal dose (classic LD50) test while achieving significant reductions in animal use. It uses sequential dosing, together with sophisticated computer-assisted computational methods during the execution and calculation phases of the test. Staircase design, a form of sequential test design, can be applied to acute toxicity testing with its binary experimental endpoints (yes/no outcomes). The improved UDP provides a point estimate of the LD50 and approximate confidence intervals in addition to observed toxic signs for the substance tested. It does not provide information about the dose-response curve. Computer simulation was used to test performance of the UDP without the need for additional laboratory validation.

  8. Vitamin A status of Filipino preschool children given a massive oral dose.

    Science.gov (United States)

    Perlas, L A; Florentino, R F; Fuertes, R T; Madriaga, J R; Cheong, R L; Desnacido, J A; Marcos, J M; Cabrera, M I

    1996-12-01

    The protection period of a 200,000 IU of vitamin A on Filipino children was determined. Subjects were 105 children aged 1-5 years given a single massive dose during the "Araw ng Sangkap Pinoy" (ASAP) in March 1995. Serum retinol was measured by HPLC at baseline, one, two, four and six months after the administration of the dose. Results showed that baseline serum retinol levels were significantly lower than all follow-up values. Serum retinol values were maintained at levels higher than pre-supplementation values although the values decreased on the second month after supplementation. The proportions of deficient and low (values at baseline were significantly lower (p values. The WHO recommendation of 200,000 IU was effective in increasing serum retinol concentrations and maintaining it above pre-supplementation levels up to 6 months after administration of the dose. It also replenished organic vitamin A reserves as shown by the dose response (S30DR) approach. Incidence of infection also decreased among the children. Supplementation with vitamin A has likewise resulted in an increase in hemoglobin values and a decrease in the proportion of anemics (Hb < 11.0 g/dl) among the children.

  9. Dose-dependent effects of oral tyrosine administration on plasma tyrosine levels and cognition in aging

    NARCIS (Netherlands)

    Rest, van de Ondine; Bloemendaal, Mirjam; Heus, De Rianne; Aarts, Esther

    2017-01-01

    The effects of tyrosine on plasma response and cognition in aging are unknown. We assessed the dose-dependent response to tyrosine administration in older adults in both plasma tyrosine concentrations and working memory performance. In this double blind randomized cross-over trial 17 older adults

  10. Dose-Dependent Effects of Oral Tyrosine Administration on Plasma Tyrosine Levels and Cognition in Aging

    NARCIS (Netherlands)

    Rest, O. van de; Bloemendaal, M.; Heus, R.A.A. de; Aarts, E.

    2017-01-01

    The effects of tyrosine on plasma response and cognition in aging are unknown. We assessed the dose-dependent response to tyrosine administration in older adults in both plasma tyrosine concentrations and working memory performance. In this double blind randomized cross-over trial 17 older adults

  11. The absorption, distribution, excretion, and metabolism of a single oral dose of O-ethyl O-4-nitrophenyl phenylphosphonothioate in hens

    International Nuclear Information System (INIS)

    Abou-Donia, M.B.; Reichert, B.L.; Ashry, M.A.

    1983-01-01

    The disposition and metabolism of a single oral 10 mg/kg (LD50) of uniformly phenyl-labeled [ 14 C]EPN (O-ethyl O-4-nitrophenyl [ 14 C]phenylphosphonothioate) were studied in adult hens. The birds were protected from acute toxicity with atropine sulfate. Three treated hens were killed at each time interval (days): 0.5, 2, 4, 8, 12. Radioactivity was adsorbed from the gastrointestinal tract and distributed in all tissues. Most of the dose was excreted in the combined urinary-fecal excreta (74%). Only traces of the radioactivity (0.2%) were detected in expired CO 2 . Most of the excreted radioactive materials were identified as phenylphosphonic acid (PPA), O-ethyl phenylphosphonic acid (EPPA), and O-ethyl phenylphosphonothioc acid (EPPTA). Radioactivity in tissues reached a peak of 11.8% in 12 days. The highest concentration of radioactivity was present in the liver followed by bile, kidney, adipose tissue, and muscle. EPN was the major compound identified in brain, spinal cord, sciatic nerve, kidney, and plasma. Most of the radioactivity in the liver was identified as EPPA followed by EPPTA and PPA. Kinetic studies showed that EPN disappeared exponentially from tissues. The half-life of the elimination of EPN from plasma was 16.5 days corresponding to a constant rate value of 0.04 day-1. Relative residence (RR) of EPN relative to plasma was shortest in liver and longest in adipose tissue followed by sciatic nerve and spinal cord

  12. Treatment of recalcitrant erosive oral lichen planus and desquamative gingivitis with oral apremilast.

    Science.gov (United States)

    AbuHilal, Mohn'd; Walsh, Scott; Shear, Neil

    2016-11-30

    Erosive oral lichen planus and desquamative gingivitis are uncommon but severe debilitating variants of oral lichen planus. Treatment of these presentations is difficult and challenging. A 44-year-old woman was referred to the dermatology clinic with chronic painful lichen planus-related gingivitis and buccal erosions. She has failed multiple treatments including topical clobetasol and tacrolimus, intralesional corticosteroids and several systemic and immunosuppressive agents. Following completion of three months of treatment with oral apremilast at a dose of 30 mg twice daily, significant improvement was noted in her disease activity. Oral apremilast may be a safe and effective treatment for erosive oral lichen planus.

  13. Gonad doses for male patients from stomach examination and oral cholegraphy using the X-ray image intensifying technique and television fluoroscopy

    International Nuclear Information System (INIS)

    Steinbach, W.; Richter, K.; Koenig, W.; Menzel, B.; Reisinger, W.; Uhlich, F.

    1979-01-01

    The gonad dose was measured for male patients undergoing stomach examinations and oral cholegraphy by means of a diagnostic twelve pulse generator (TuR D 1500) and an X-ray apparatus 'Diagnost 100' (Philips-Mueller). In a small group of patients the gonad dose was ascertained per exposure to a 70 mm single spot film, to a 24 cm x 30 cm full size radiograph, and per minute of exposure to image intensifier fluoroscopy. The total gonad dose in both the diagnostic techniques was determined seperately in larger groups of patients. In stomach examination large size radiography led to a gonad dose 20 times higher than that obtained with the spot film technique, while exposure from cholegraphy was 10 times higher. The gonad dose per exposure of a single spot film was about 0.5 mrad. In examinations of the stomach the gonad dose from one minute fluroscopy was 18 times higher than the doses determined for a single spot film, and in cholegraphy it was 10 times higher. Supposing mean values of the number of radiographs and of the fluoroscopy time according to the conditions applied, the gonad dose in stomach examination from the film-screen technique is about twice that from the television image-intensifying technique. By comparison, oral cholegraphy exclusively performed by large-size radiography yielded about the same gonad dose as the spot film television technique. Total dose values determined separately confirmed these evaluations. (author)

  14. Evaluation of radioprotection conditions and patient dose in thorax exams carried out in a public children's hospital in Belo Horizonte, MG, Brazil

    International Nuclear Information System (INIS)

    Lacerda, Marco A.S.; Silva, Teogenes A. da; Guedes, Elton C.; Khoury, Helen J.; Azevedo, Ana C.P.

    2005-01-01

    We conducted a survey of the conditions of radiation protection, radiographic techniques, dose and risk for pediatric patients undergoing chest X-rays exams in a children's hospital in Belo Horizonte-MG, Brazil. From a total of 125 chest exams (projections AP and PA) were noted the patient data (gender, weight, and age) and parameters of radiographic technique (kV, mAs and distance focus-skin). I was also evaluated the working procedures and the conditions of radiation protection. The values of input air kerma (K a,e ) and effective dose (E) were determined using the DoseCal software developed by Radiological Protection Center of Saint Georges's Hospital in London. With respect to the procedures and conditions for radiation protection, many aspects of Portaria 453 are not considered. The use of radiographic techniques with high values of mAs and low voltage values are not according with the quality criteria adopted by the European Community (EC). The values of Ka for patients aged 1 to 5 years varied between 51 μGy and 64 μGy, below the reference levels proposed by the EC. For patients over 5 years old, the values of Ka were substantially higher than those for other patients. The results allow to conclude that there is a need for optimization of the procedures adopted in order to reduce the dose and the risk to patients

  15. Monte Carlo calculations for doses in organs and tissues to oral radiography

    International Nuclear Information System (INIS)

    Sampaio, E.V.M.

    1985-01-01

    Using the MIRD 5 phantom and Monte Carlo technique, organ doses in patients undergoing external dental examination were calculated taking into account the different x-ray beam geometries and the various possible positions of x-ray source with regard to the head of the patient. It was necessary to introduce in the original computer program a new source description specific for dental examinations. To have a realistic evaluation of organ doses during dental examination it was necessary to introduce a new region in the phantom heat which characterizes the teeth and salivary glands. The attenuation of the x-ray beam by the lead shield of the radiographic film was also introduced in the calculation. (author)

  16. Population pharmacokinetic model of THC integrates oral, intravenous, and pulmonary dosing and characterizes short- and long-term pharmacokinetics.

    Science.gov (United States)

    Heuberger, Jules A A C; Guan, Zheng; Oyetayo, Olubukayo-Opeyemi; Klumpers, Linda; Morrison, Paul D; Beumer, Tim L; van Gerven, Joop M A; Cohen, Adam F; Freijer, Jan

    2015-02-01

    Δ(9)-Tetrahydrocannobinol (THC), the main psychoactive compound of Cannabis, is known to have a long terminal half-life. However, this characteristic is often ignored in pharmacokinetic (PK) studies of THC, which may affect the accuracy of predictions in different pharmacologic areas. For therapeutic use for example, it is important to accurately describe the terminal phase of THC to describe accumulation of the drug. In early clinical research, the THC challenge test can be optimized through more accurate predictions of the dosing sequence and the wash-out between occasions in a crossover setting, which is mainly determined by the terminal half-life of the compound. The purpose of this study is to better quantify the long-term pharmacokinetics of THC. A population-based PK model for THC was developed describing the profile up to 48 h after an oral, intravenous, and pulmonary dose of THC in humans. In contrast to earlier models, the current model integrates all three major administration routes and covers the long terminal phase of THC. Results show that THC has a fast initial and intermediate half-life, while the apparent terminal half-life is long (21.5 h), with a clearance of 38.8 L/h. Because the current model characterizes the long-term pharmacokinetics, it can be used to assess the accumulation of THC in a multiple-dose setting and to forecast concentration profiles of the drug under many different dosing regimens or administration routes. Additionally, this model could provide helpful insights into the THC challenge test used for the development of (novel) compounds targeting the cannabinoid system for different therapeutic applications and could improve decision making in future clinical trials.

  17. A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles.

    Science.gov (United States)

    Kurosawa, Yuko; Nirengi, Shinsuke; Homma, Toshiyuki; Esaki, Kazuki; Ohta, Mitsuhiro; Clark, Joseph F; Hamaoka, Takafumi

    2015-06-25

    Our aim was to determine the quantitative effects of a single-dose of Nattokinase (NK) administration on coagulation/fibrinolysis parameters comprehensively in healthy male subjects. A double-blind, placebo-controlled cross-over NK intervention study was carried out in 12 healthy young males. Following the baseline blood draw, each subject was randomized to receive either a single-dose of 2,000 FU NK (NSK-SD, Japan Bio Science Laboratory Co., Ltd) or placebo with subsequent cross-over of the groups. Subjects donated blood samples at 2, 4, 6 and 8 hours following administration for analysis of coagulation/fibrinolysis parameters. As a result, D-dimer concentrations at 6, and 8 hours, and blood fibrin/fibrinogen degradation products at 4 hours after NK administration elevated significantly (p < 0.05, respectively). Factor VIII activity declined at 4 and 6 hours (p < 0.05, respectively), blood antithrombin concentration was higher at 2 and 4 hours (p < 0.05, respectively), and the activated partial thromboplastin time prolonged significantly at 2 and 4 hours following NK administration (p < 0.05 and p < 0.01, respectively). All the changes, however, were within the normal range. In conclusion, thus, a single-dose of NK administration appears enhancing fibrinolysis and anti-coagulation via several different pathways simultaneously.

  18. Knowledge of users of low-dose oral combined contraceptives about the method

    Directory of Open Access Journals (Sweden)

    Camila Félix Américo

    2013-07-01

    Full Text Available OBJECTIVES: to identify the knowledge of users of combined oral contraceptive about correct use, side effects and complications; to verify the correlation between knowledge about the method with age, education, family income and time of use. METHOD: cross-sectional study performed in Fortaleza, Ceará, Brazil, from March to July 2010, with 294 women. Data were collected through interviews. RESULTS: 75% had substantial knowledge about the proper use and side effects and no knowledge about complications. The higher the educational level and family income, the higher the women's knowledge about the correct use of the method. Positive correlation suggests that women who used the method for longer knew more about its side effects. CONCLUSION: there are knowledge gaps about the method, which are influenced by socioeconomic variables and use time.

  19. Infection and immunity in Down syndrome: a trial of long-term low oral doses of zinc.

    Science.gov (United States)

    Lockitch, G; Puterman, M; Godolphin, W; Sheps, S; Tingle, A J; Quigley, G

    1989-05-01

    To determine whether orally administered zinc supplements could correct the abnormal humoral and cell-mediated immunity of Down syndrome, we randomly assigned 64 children with Down syndrome, aged 1 to 19 years and living at home, to receive either zinc gluconate or placebo daily for 6-month periods with crossover from one regimen to another. Control subjects were siblings and age-matched, unrelated children. Serum zinc, copper, and measures of immune system competence were tested at 3- or 6-month intervals. Parents kept daily logs of clinical symptoms such as cough and diarrhea and of physician visits. Mean serum zinc concentrations increased to about 150% of baseline during zinc supplementation, but we found no effect on serum levels of copper, immunoglobulins, or complement; on lymphocyte number or subset distribution; or on in vitro response to mitogens. Children with Down syndrome who were receiving zinc had a trend toward fewer days or episodes of cough and fever but no change in other clinical variables. Long-term, low-dose oral zinc supplementation to improve depressed immune response or to decrease infections in children with Down syndrome cannot be recommended.

  20. Delayed Dosing of Oral Rotavirus Vaccine Demonstrates Decreased Risk of Rotavirus Gastroenteritis Associated With Serum Zinc: A Randomized Controlled Trial.

    Science.gov (United States)

    Colgate, E Ross; Haque, Rashidul; Dickson, Dorothy M; Carmolli, Marya P; Mychaleckyj, Josyf C; Nayak, Uma; Qadri, Firdausi; Alam, Masud; Walsh, Mary Claire; Diehl, Sean A; Zaman, K; Petri, William A; Kirkpatrick, Beth D

    2016-09-01

    Rotavirus is the world's leading cause of childhood diarrheal death. Despite successes, oral rotavirus vaccines are less effective in developing countries. In an urban slum of Dhaka, we performed active diarrhea surveillance to evaluate monovalent G1P[8] rotavirus vaccine (RV1) efficacy and understand variables contributing to risk of rotavirus diarrhea (RVD). We performed a randomized controlled trial of monovalent oral rotavirus vaccine (RV1). Seven hundred healthy infants received RV1 or no RV1 (1:1) using delayed dosing (10 and 17 weeks) and were followed for 1 year. Intensive diarrhea surveillance was performed. The primary outcome was ≥1 episode of RVD. Nutritional, socioeconomic, and immunologic factors were assessed by logistic regression best-subsets analysis for association with risk of RVD and interactions with vaccine arm. Incidence of all RVD was 38.3 cases per 100 person-years. Per-protocol RV1 efficacy was 73.5% (95% confidence interval [CI], 45.8%-87.0%) against severe RVD and 51% (95% CI, 33.8%-63.7%) against all RVD. Serum zinc level (odds ratio [OR], 0.77; P = .002) and lack of rotavirus immunoglobulin A (IgA) seroconversion (OR, 1.95; P = .018) were associated with risk of RVD, independent of vaccination status. Water treatment and exclusive breastfeeding were of borderline significance. Factors not associated with RVD included height for age at 10 weeks, vitamin D, retinol binding protein, maternal education, household income, and sex. In an urban slum with high incidence of RVD, the efficacy of RV1 against severe RVD was higher than anticipated in the setting of delayed dosing. Lower serum zinc level and lack of IgA seroconversion were associated with increased risk of RVD independent of vaccination. NCT01375647. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  1. Doses to LiF :Ti, Mg chips encapsulated in plastic extremity rings as a result of radon gas exposure

    International Nuclear Information System (INIS)

    Kearfott, Kimberlee J; Noon, Evan P; Rafique, Muhammad

    2015-01-01

    Previous studies measured the effects of 222 Rn on various thermoluminescent dosemeters (TLDs). This study quantified the effects of 222 Rn on LiF : Ti,Mg chips encapsulated in plastic extremity rings. For 28 d, one batch of TLDs was left in a chamber with high radon levels, and another batch in a control chamber with normal background radon levels. A few TLDs in each batch were removed from the rings for direct exposure to the ambient air in each chamber. Passive continuous radon monitors (CRMs) recorded the 222 Rn levels. TLDs were processed using a third-party dosimetry company, CRM data were analysed, and the relationship between integrated 222 Rn concentration and TLD response was determined. The batch of TLDs in the experimental chamber showed a weak response to 222 Rn gas, which was in the order of 0.5 nSv Bq −1  m 3  d −1 . (paper)

  2. Pharmacokinetics of colistin and colistimethate sodium after a single 80-mg intravenous dose of CMS in young healthy volunteers.

    Science.gov (United States)

    Couet, W; Grégoire, N; Gobin, P; Saulnier, P J; Frasca, D; Marchand, S; Mimoz, O

    2011-06-01

    Colistin pharmacokinetics (PK) was investigated in young healthy volunteers after a 1-h infusion of 80 mg (1 million international units (MIU)) of the prodrug colistin methanesulfonate (CMS). Concentration levels of CMS and colistin were determined in plasma and urine using a new chromatographic assay and analyzed simultaneously with a population approach after correcting the urine-related data for postexcretion hydrolysis of CMS into colistin. CMS and colistin have low volumes of distribution (14.0 and 12.4 liters, respectively), consistent with distribution being restricted to extracellular fluid. CMS is mainly excreted unchanged in urine (70% on average), with a typical renal clearance estimated at 103 ml/min-close to the glomerular filtration rate. Colistin elimination is essentially extrarenal, given that its renal clearance is 1.9 ml/min, consistent with extensive reabsorption. Colistin elimination is not limited by the formation rate because its half-life (3 h) is longer than that of CMS. The values of these pharmacokinetic parameters will serve as reference points for future comparisons with patients' data.

  3. Pharmacokinetics of marbofloxacin in pigs after intravenous and intramuscular administration of a single dose of 8 mg/kg: dose proportionality, influence of the age of the animals and urinary elimination.

    Science.gov (United States)

    Schneider, M; Paulin, A; Dron, F; Woehrlé, F

    2014-12-01

    The pharmacokinetics of marbofloxacin in pigs were evaluated as a function of dose and animal age following intravenous and intramuscular administration of a 16% solution (Forcyl(®) ). The absolute bioavailability of marbofloxacin as well as the dose proportionality was evaluated in 27-week-old fattening pigs. Blood PK and urinary excretion of marbofloxacin were evaluated after a single intramuscular dose of 8 mg/kg in 16-week-old male pigs. An additional group of 12-week-old weaned piglets was used for the evaluation of age-related kinetics. The plasma and urine concentration of marbofloxacin was determined using a HPLC method. Pharmacokinetic parameters were calculated using noncompartmental methods. After intravenous administration in 27-week-old fattening pigs, the total body clearance was 0.065 L/h·kg. After intramuscular administration to the same animals, the mean observed Cmax was 6.30 μg/mL, and the AUCINF was 115 μg·h/mL. The absolute bioavailability was 91.5%, and dose proportionality was shown within the dose range of 4-16 mg/kg. The renal clearance was about half of the value of the total clearance. The total systemic clearance values significantly decreased as a function of age, being 0.092 L/h·kg and 0.079 L/h·kg in pigs aged 12 and 16 weeks, respectively. © 2014 The Authors. Journal of Veterinary Pharmacology and Therapeutics Published by John Wiley & Sons Ltd.

  4. Short-term assessment of left ventricular function, coronary hemodynamics, and catecholamine balance in severe congestive heart failure after a single oral dose of milrinone

    NARCIS (Netherlands)

    F. Piscione; B.E. Jaski; P.W.J.C. Serruys (Patrick)

    1988-01-01

    textabstractSystemic and coronary hemodynamics were measured before and every 10 min after oral milrinone (10 mg) administration for 50 min, together with the drug plasma level in 14 patients with congestive heart failure. Left ventricular pressure (tip manometry), volume (angiography), and derived

  5. Making the leap from daily oral dosing to long-acting injectables: lessons from the antipsychotics.

    Science.gov (United States)

    Remenar, Julius F

    2014-06-02

    There are now long-acting versions of six antipsychotic drugs on the U.S. market, and with them, five unique combinations of molecular form and delivery strategy long-acting-injectable-antipsychotics (LAIAs) show evidence of reduced relapses of schizophrenia, but their introduction has been slow, taking at least nine years after the approval of each oral drug. Oily solutions of lipophilic prodrugs were the first to enter the LAIA market, but they relied on esterification of a hydroxyl handle that was lost with the emergence of the atypical antipsychotics. A review of the literature and patents shows that companies tested many different approaches before reaching the currently marketed versions, including aqueous suspensions of poorly soluble salts, polymeric microspheres, and new approaches to making prodrugs. Yet, very little has been published to support faster development of safe long-acting injectables (LAIs). This review introduces some of the critical considerations in creating an LAI; then it analyzes the existing products and discusses areas where further research is needed. The available literature suggests that lipophilic prodrugs may be inherently safer than poorly soluble salts as LAIs. Other areas needing additional study include (1) the range of physical properties acceptable for LAIs and the effect of prodrug tail length in achieving them, and (2) the role of physiological responses at the injection site in the release of drug from a depot.

  6. Emprego de altas doses de amiodarona via oral na reversão da fibrilação atrial no pós-operatório de cirurgia cardíaca High dose amiodarone for the reversion of atrial fibrillation during the postoperative period of cardiac surgery

    Directory of Open Access Journals (Sweden)

    João Carlos Vieira da Costa Guaragna

    1997-12-01

    Full Text Available OBJETIVO: Relatar a experiência no emprego de altas doses de amiodarona via oral (1800mg/d na reversão da fibrilação atrial (FA em pacientes submetidos à cirurgia cardíaca. MÉTODOS: Analisados, retrospectivamente, 80 pacientes que apresentaram FA no pós operatório de cirurgia cardíaca, constituindo 2 grupos: grupo A com 28 pacientes em uso de amiodarona e grupo B recebendo digital, sendo que este grupo foi subdividido no grupo C com 21 pacientes onde foi associada amiodarona, quando não houvesse reversão da arritmia em 48h. As diferenças foram consideradas significativas para um valor de PPURPOSE: To report our experience using high dose oral amiodarone (1,800mg/day for the reversion of atrial fibrillation to sinus rhythm in patients submitted to cardiac surgery. METHODS: We retrospectively analyzed the records of 80 patients who had atrial fibrillation during the postoperative period after cardiac surgery, initially divided in two groups: group A, 28 patients that used amiodarone, and group B composed of patients receiving digoxin. The latter group was divided further in a third group (C, with 21 patients in which amiodarone was associated with digoxin if there was no reversion of the arrhythmia after 48 hours of treatment. The observed differences were considered significant at P<0.05. RESULTS: Atrial fibrillation occurred in 19.4% of the patients submitted to surgery, predominating in males, 60 to 69 years-old. In group A there was reversion to sinus rhythm in 78.6% of the cases. In group B digoxin succeeded in 60%, and in group C 90% of the patients reverted to sinus rhythm. CONCLUSION: High dose oral amiodarone, alone or combined to digoxin, can be safe and effective for the treatment of atrial fibrillation after cardiac surgery.

  7. Therapeutic Doses of Nonsteroidal Anti-Inflammatory Drugs Inhibit Osteosarcoma MG-63 Osteoblast-Like Cells Maturation, Viability, and Biomineralization Potential

    Science.gov (United States)

    De Luna-Bertos, E.; Ramos-Torrecillas, J.; García-Martínez, O.; Guildford, A.; Santin, M.; Ruiz, C.

    2013-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used to reduce pain and inflammation. However, their effect on bone metabolisms is not well known, and results in the literature are contradictory. The present study focusses on the effect of dexketoprofen, ketorolac, metamizole, and acetylsalicylic acid, at therapeutic doses, on different biochemical and phenotypic pathways in human osteoblast-like cells. Osteoblasts (MG-63 cell line) were incubated in culture medium with 1–10 μM of dexketoprofen, ketorolac, metamizole, and acetylsalicylic acid. Flow cytometry was used to study antigenic profile and phagocytic activity. The osteoblastic differentiation was evaluated by mineralization and synthesis of collagen fibers by microscopy and alkaline phosphatase activity (ALP) by spectrophotometric assay. Short-term treatment with therapeutic doses of NSAIDs modulated differentiation, antigenic profile, and phagocyte activity of osteoblast-like cells. The treatment reduced ALP synthesis and matrix mineralization. However, nonsignificant differences were observed on collagen syntheses after treatments. The percentage of CD54 expression was increased with all treatments. CD80, CD86, and HLA-DR showed a decreased expression, which depended on NSAID and the dose applied. The treatments also decreased phagocyte activity in this cellular population. The results of this paper provide evidences that NSAIDs inhibit the osteoblast differentiation process thus reducing their ability to produce new bone mineralized extracellular matrix. PMID:24170983

  8. Therapeutic Doses of Nonsteroidal Anti-Inflammatory Drugs Inhibit Osteosarcoma MG-63 Osteoblast-Like Cells Maturation, Viability, and Biomineralization Potential

    Directory of Open Access Journals (Sweden)

    E. De Luna-Bertos

    2013-01-01

    Full Text Available Nonsteroidal anti-inflammatory drugs (NSAIDs are frequently used to reduce pain and inflammation. However, their effect on bone metabolisms is not well known, and results in the literature are contradictory. The present study focusses on the effect of dexketoprofen, ketorolac, metamizole, and acetylsalicylic acid, at therapeutic doses, on different biochemical and phenotypic pathways in human osteoblast-like cells. Osteoblasts (MG-63 cell line were incubated in culture medium with 1–10 μM of dexketoprofen, ketorolac, metamizole, and acetylsalicylic acid. Flow cytometry was used to study antigenic profile and phagocytic activity. The osteoblastic differentiation was evaluated by mineralization and synthesis of collagen fibers by microscopy and alkaline phosphatase activity (ALP by spectrophotometric assay. Short-term treatment with therapeutic doses of NSAIDs modulated differentiation, antigenic profile, and phagocyte activity of osteoblast-like cells. The treatment reduced ALP synthesis and matrix mineralization. However, nonsignificant differences were observed on collagen syntheses after treatments. The percentage of CD54 expression was increased with all treatments. CD80, CD86, and HLA-DR showed a decreased expression, which depended on NSAID and the dose applied. The treatments also decreased phagocyte activity in this cellular population. The results of this paper provide evidences that NSAIDs inhibit the osteoblast differentiation process thus reducing their ability to produce new bone mineralized extracellular matrix.

  9. Reducing the oral contrast dose in CT colonography: evaluation of faecal tagging quality and patient acceptance

    International Nuclear Information System (INIS)

    Liedenbaum, M.H.; Denters, M.J.; Zijta, F.M.; Ravesteijn, V.F. van; Bipat, S.; Vos, F.M.; Dekker, E.; Stoker, J.

    2011-01-01

    Aim: To evaluate the minimal iodine contrast medium load necessary for an optimal computed tomography colonography tagging quality. Materials and Methods: Faecal occult blood test positive patients were randomly selected for one of three iodine bowel preparations: (1) 3 x 50 ml meglumine ioxithalamate (45 g iodine), (2) 4 x 25 ml meglumine ioxithalamate (30 g iodine); or (3) 3 x 25 ml (22.5 g iodine) meglumine ioxithalamate. Two experienced readers assessed the tagging quality per colonic segment on a five-point scale and the presence of adherent stool. Also semi-automatic homogeneity measurements were performed. Patient acceptance was assessed with questionnaires. Results: Of 70 eligible patients, 45 patients participated (25 males, mean age 62 years). Each preparation group contained 15 patients. The quality of tagging was insufficient (score 1-2) in 0% of segments in group 1; 4% in group 2 (p < 0.01 versus group 1); and 5% in group 3 (p = 0.06 versus group 1). In group 1 in 11% of the segments adherent stool was present compared with 49% in group 2 and 41% in group 3 (p < 0.01, group 2 and 3 versus group 1). Homogeneity was 85, 102 (p < 0.01), and 91 SD HU (p = 0.26) in groups 1, 2, and 3, respectively. In group 1 two patients experienced no burden after contrast agent ingestion compared to one patient in group 2 and nine patients in group 3 (p = 0.017). Conclusion: A dose of 3 x 50 ml meglumine ioxithalamate is advisable for an optimal tagging quality despite beneficial effects on the patient acceptance in patients receiving a lower dose.

  10. Repeated dose 28-day oral toxicity study in Wistar rats with a mixture of five pesticides often found as residues in food: alphacypermethrin, bromopropylate, carbendazim, chlorpyrifos and mancozeb

    DEFF Research Database (Denmark)

    Jacobsen, H.; Østergaard, G.; Lam, Henrik Rye

    2004-01-01

    Six dose groups of 8 male and female rats respectively received a daily dose equivalent to 0, 0.15, 0.006, 0.03, 0.15 or 0.3 mg/kg b.w./day chlorpyrifos (groups 1-6) and the last four dose groups (groups 3-6) received in addition daily doses equivalent to 18 mg/kg b.w./day alphacypermethrin, 30 mg...... of acetylcholinesterase activity in plasma and brain by chlorpyrifos was not enhanced by coadministration of the other four pesticides. Effects were seen in liver, thyroid, thymus and blood in the combination groups. However, identification of the pesticide(s) responsible for these changes would require further studies...

  11. The effect of pre-dose on thermally and optically stimulated luminescence from α-Al2O3:C,Mg and α-Al2O3:C.

    Science.gov (United States)

    Kalita, J M; Chithambo, M L

    2018-06-15

    We report the effect of pre-dose on the thermoluminescence (TL) and optically stimulated luminescence (OSL) dose response of α-Al 2 O 3 :C,Mg and α-Al 2 O 3 :C. Before any luminescence measurement, the samples were irradiated with different doses, namely 100, 500 and 1000 Gy to populate the deep electron traps. This is the pre-dose. The results from TL and OSL studies are compared with results from samples used without any pre-measurement dose. The TL glow curves and OSL decay curves of α-Al 2 O 3 :C,Mg recorded after pre-doses of 100, 500 and 1000 Gy are identical to those from a sample used without any pre-dose. Further, the TL and OSL dose response of all α-Al 2 O 3 :C,Mg samples are similar regardless of pre-dose. In comparison, the TL glow curves and OSL decay curves of α-Al 2 O 3 :C are influenced by pre-dose. We conclude that the differences in the TL and OSL dose response of various pre-dosed samples of α-Al 2 O 3 :C are due to the concentration of charge in the deep traps. On the other hand, owing to the lower concentration of such deep traps in α-Al 2 O 3 :C,Mg, the TL or OSL dose responses are not affected by pre-dose in this material. Copyright © 2018 Elsevier Ltd. All rights reserved.

  12. Effects of acute and repeated oral doses of D-tagatose on plasma uric acid in normal and diabetic humans.

    Science.gov (United States)

    Saunders, J P; Donner, T W; Sadler, J H; Levin, G V; Makris, N G

    1999-04-01

    D-tagatose, a stereoisomer of D-fructose, is a naturally occurring ketohexose proposed for use as a low-calorie bulk sweetener. Ingested D-tagatose appears to be poorly absorbed. The absorbed portion is metabolized in the liver by a pathway similar to that of D-fructose. The main purpose of this study was to determine if acute or repeated oral doses of D-tagatose would cause elevations in plasma uric acid (as is seen with fructose) in normal humans and Type 2 diabetics. In addition, effects of subchronic D-tagatose ingestion on fasting plasma phosphorus, magnesium, lipids, and glucose homeostasis were studied. Eight normal subjects and eight subjects with Type 2 diabetes participated in this two-phase study. Each group was comprised of four males and four females. In the first phase, all subjects were given separate 75 g 3-h oral glucose and D-tagatose tolerance tests. Uric acid, phosphorus, and magnesium were determined in blood samples collected from each subject at 0, 30, 60, 120, and 180 min after dose. In the 8-week phase of the study, the normals were randomly placed into two groups which received 75 g of either D-tagatose or sucrose (25 g with each meal) daily for 8 weeks. The diabetics were randomized into two groups which received either 75 g D-tagatose or no supplements of sugar daily for 8 weeks. Uric acid, phosphorus, magnesium, lipids, glycosylated hemoglobin, glucose, and insulin were determined in fasting blood plasma of all subjects at baseline (time zero) and biweekly over the 8 weeks. The 8-week test did not demonstrate an increase in fasting plasma uric acid in response to the daily intake of D-tagatose. However, a transient increase of plasma uric acid levels was observed after single doses of 75 g of D-tagatose in the tolerance test. Plasma uric acid levels were found to rise and peak at 60 min after such dosing. No clinical relevance was attributed to this treatment-related effect because excursions of plasma uric acid levels above the normal

  13. A Single-Dose, Single-Period Pharmacokinetic Assessment of an Extended-Release Orally Disintegrating Tablet of Methylphenidate in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder.

    Science.gov (United States)

    Childress, Ann; Newcorn, Jeffrey; Stark, Jeffrey G; McMahen, Russ; Tengler, Mark; Sikes, Carolyn

    2016-08-01

    To determine the pharmacokinetic (PK) profile of a proprietary formulation of methylphenidate (MPH) in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) in a phase 1 study. Methylphenidate extended-release orally disintegrating tablets (MPH XR-ODTs) combine two technologies in a single-tablet formulation-an extended-release profile that was designed for once-daily dosing in an ODT that does not require water or chewing for ingestion. This was a single-dose, open-label, single-period, single-treatment study, in which 32 children with ADHD who were receiving MPH in doses of 40 or 60 mg before beginning the study each received a 60-mg dose (2 × 30 mg) of MPH XR-ODT. The following plasma PK parameters of MPH were determined for participants grouped by age (6-7, 8-9, 10-12, and 13-17 years old): maximum concentration (Cmax), time to maximum concentration (Tmax), elimination half-life (T½), area under the curve from 0 hours to infinity (AUCinf), oral clearance (CL/F), and volume of distribution in the terminal phase (Vz/F). Safety and tolerability were also assessed. A total of 32 participants received the study drug. For all participants, plasma concentration-time profiles of MPH exhibited a broad peak after administration of MPH XR-ODT through ∼8 hours, indicating extended release from the formulation, followed by an apparent first-order elimination phase. As age increased, MPH exposure decreased and mean estimates of CL/F increased; however, weight-normalized CL/F values were comparable across age groups. Similarly, mean estimates of Vz/F increased with age, but weight-normalization decreased differences across age groups, with the exception of the youngest age group, which had higher values. All adverse events (AEs) were mild. This XR-ODT formulation of MPH demonstrated weight-normalized clearance rates that were consistent across all age groups, a PK profile consistent with once-daily dosing, and an AE profile consistent with

  14. Effect of treatment with single total-dose intravenous iron versus daily oral iron(III-hydroxide polymaltose on moderate puerperal iron-deficiency anemia

    Directory of Open Access Journals (Sweden)

    Iyoke CA

    2017-05-01

    Full Text Available Chukwuemeka Anthony Iyoke,1 Fausta Chioma Emegoakor,1 Euzebus Chinonye Ezugwu,1 Lucky Osaheni Lawani,2 Leonard Ogbonna Ajah,1 Jude Anazoeze Madu,3 Hyginus Uzo Ezegwui,1 Frank Okechukwu Ezugwu4 1Department of Obstetrics and Gynaecology, University of Nigeria, Enugu Campus, 2Department of Obstetrics and Gynaecology, Federal Teaching Hospital, Abakaliki, 3Department of Haematology, University of Nigeria, Nsukka, 4Department of Obstetrics and Gynaecology, College of Medicine, Enugu State University, Enugu, Nigeria Background: Iron-deficiency anemia is the most common nutritional cause of anemia in pregnancy and is often responsible for puerperal anemia. Puerperal anemia can impair postpartum maternal and neonatal well-being. Objective: To determine the effect of treatment of moderate puerperal iron-deficiency anemia using a single intravenous total-dose iron dextran versus daily single dose oral iron(III-hydroxide polymaltose. Methodology: A randomized controlled study in which postpartum women with moderate iron-deficiency anemia were randomized into treatment with either a single total-dose intravenous iron dextran or with daily single doses of oral iron(III-hydroxide polymaltose tablets for 6 weeks. Effects on hemoglobin concentration using either method were compared at 6 weeks postpartum. Analysis was per protocol using SPSS version 17 for windows. P-values ≤0.05 were considered significant. Results: Two hundred eighty-four women were recruited for the study: 142 women received single total dose intravenous infusion of iron dextran while 142 received daily oral iron(III-hydroxide polymaltose tablets. Approximately 84.0% (237/282 completed the study and were analyzed including 81% (115/142 of those randomized to injectable iron therapy compared to 85.9% (122/142 of those randomized to oral treatment. The proportions of women who had attained hemoglobin concentration of at least 10 g/dL by the 6 weeks postpartum visit did not differ

  15. Evaluation of oral abdominal contrast agent containing ferric ammonium citrate

    International Nuclear Information System (INIS)

    Shiga, Toshiko; Kawamura, Yasutaka; Iwasaki, Toshiko

    1991-01-01

    We evaluated the effectiveness of oral MRI contrast agent containing ferric ammonium citrate. Twenty patients were arbitrarily divided into 2 groups according to the given dose of 100 and 200 mg Fe of oral MRI contrast agent. MRI was performed before and immediately after ingesting 300 ml solution of oral MRI contrast agent using a 1.5 T superconducting system (GE: Signa). Each dose of 100 and 200 mg Fe of oral MRI contrast agent produced sufficient enhancement of gastrointestinal tract, enough to make clear the pancreatic contour and porta hepatis. There was no significant change in blood and urine analysis observed after taking oral MRI contrast agent. The use of ferric ammonium citrate as an oral MRI contrast agent seems to add valuable information in performing upper abdominal MRI imaging. (author)

  16. Does radiation dose to the salivary glands and oral cavity predict patient-rated xerostomia and sticky saliva in head and neck cancer patients treated with curative radiotherapy?

    International Nuclear Information System (INIS)

    Jellema, Anke Petra; Doornaert, Patricia; Slotman, Ben J.; Rene Leemans, C.; Langendijk, Johannes A.

    2005-01-01

    Background and Purpose: To investigate the association between the mean salivary gland and oral cavity dose, with patient-rated moderate and severe xerostomia and sticky saliva. Patients and methods: One hundred and fifty-seven patients treated with bilateral irradiation for head and neck cancer were included. The parotid and submandibular glands and the oral cavity were delineated on plannings-CT scans. At baseline and 6 and 12 months self-reported xerostomia and sticky saliva were assessed using the EORTC QLQ-H and N35 questionnaire. Results: At 6 months a significant association between the mean parotid (MD par ) and mean submandibular dose (MD subm ) and xerostomia was observed (OR-MD par : 1.17; P=0.002 and OR-MD subm : 1.08; P=0.02). Between MD par and MD subm , a significant interaction term was present. No significant association was found with the oral cavity dose. Xerostomia was reversible depending on MD par and MD subm . Considering Sticky saliva, a significant association was found at 6 and 12 months with MD subm (OR: 1.03; P par and MD subm influence the risk of xerostomia in irradiated patients at 6 months. This probability as a function of the mean parotid dose significantly depended on the mean dose in the submandibular glands. Sticky saliva mainly depends on MD subm

  17. SU-D-16A-02: A Novel Methodology for Accurate, Semi-Automated Delineation of Oral Mucosa for Radiation Therapy Dose-Response Studies

    International Nuclear Information System (INIS)

    Dean, J; Welsh, L; Gulliford, S; Harrington, K; Nutting, C

    2014-01-01

    Purpose: The significant morbidity caused by radiation-induced acute oral mucositis means that studies aiming to elucidate dose-response relationships in this tissue are a high priority. However, there is currently no standardized method for delineating the mucosal structures within the oral cavity. This report describes the development of a methodology to delineate the oral mucosa accurately on CT scans in a semi-automated manner. Methods: An oral mucosa atlas for automated segmentation was constructed using the RayStation Atlas-Based Segmentation (ABS) module. A radiation oncologist manually delineated the full surface of the oral mucosa on a planning CT scan of a patient receiving radiotherapy (RT) to the head and neck region. A 3mm fixed annulus was added to incorporate the mucosal wall thickness. This structure was saved as an atlas template. ABS followed by model-based segmentation was performed on four further patients sequentially, adding each patient to the atlas. Manual editing of the automatically segmented structure was performed. A dose comparison between these contours and previously used oral cavity volume contours was performed. Results: The new approach was successful in delineating the mucosa, as assessed by an experienced radiation oncologist, when applied to a new series of patients receiving head and neck RT. Reductions in the mean doses obtained when using the new delineation approach, compared with the previously used technique, were demonstrated for all patients (median: 36.0%, range: 25.6% – 39.6%) and were of a magnitude that might be expected to be clinically significant. Differences in the maximum dose that might reasonably be expected to be clinically significant were observed for two patients. Conclusion: The method developed provides a means of obtaining the dose distribution delivered to the oral mucosa more accurately than has previously been achieved. This will enable the acquisition of high quality dosimetric data for use in

  18. A Comparative Efficacy of Low-Dose Combined Oral Contraceptives Containing Desogestrel and Drospirenone in Premenstrual Symptoms

    Directory of Open Access Journals (Sweden)

    Jirath Wichianpitaya

    2013-01-01

    Full Text Available Objective. To compare the efficacy of low-dose COC containing desogestrel (DSG with drospirenone (DRSP in the changes of premenstrual symptoms. Methods. In an open-label randomized controlled trial, 90 women with premenstrual syndrome who required COC were randomly recruited and allocated equally to receive either 6 cycles of 20 micrograms ethinyl estradiol (EE/150 micrograms DSG (DSG group or 20 micrograms EE/3 mg DRSP (DRSP group in 24/4 extended regimen. Analysis of covariance and repeated analysis of variance were used to determine the difference of mean Women's Health Assessment Questionnaire (WHAQ scores changes between groups, within group, and in premenstrual, menstrual, and postmenstrual phases. Results. Baseline characteristics and WHAQ scores were comparable. At the ends of the 3rd and the 6th cycles, mean WHAQ scores of all the 3 phases in DRSP group showed significant reduction and were significantly lower than those in DSG group. DSG group showed significant reduction in both premenstrual and menstrual phases after the 6th cycle. Adverse effects were comparable in both groups. In conclusion, low-dose COC containing either DSG or DRSP reduced premenstrual symptoms, but the latter showed greater efficacy and earlier reduction.

  19. Potential of neurotoxicity after a single oral dose of 4-bromo-, 4-chloro-, 4-fluoro- or 4-iodoaniline in rats.

    Science.gov (United States)

    Okazaki, Yoshimasa; Yamashita, Kotaro; Ishii, Hiroyuki; Sudo, Masato; Tsuchitani, Minoru

    2003-01-01

    The potential for neurotoxicity after a single oral dose of four halogenated aniline derivatives--4-bromoaniline (4-BA), 4-chloroaniline (4-CA), 4- fluoroaniline (4-FA) and 4-iodoaniline (4-IA)--was given to rats was investigated at or near the lethal dosage level. Hindlimb paralysis was found in the 4-BA, 4-CA and 4-FA groups on clinical observation, with the maximum incidence of 100% in the 4-BA and 4-FA groups and 66.7% in the 4-CA group. Detailed clinical observations with functional tests identified the following effects: reduced response of hindlimb extensor thrust, gait abnormality in the open field and decreased grip strength in the fore- or hindlimbs in the 4-BA, 4-CA and 4-FA groups; decreased number of supported rearing episodes in the open field in the 4-BA and 4-CA groups; abnormal landing in the aerial righting reflex in the 4-BA and 4-FA groups; and prolonged surface righting reflex in the 4-BA group. Spongy change in the white matter of the spinal cord and brainstem and nerve fibre degeneration in the peripheral nerves were found in all haloaniline-treated groups. The central and peripheral nervous systems were most severely affected in the 4-BA group and the lesions in the 4-IA group were limited in grade. This study demonstrates that a bolus dose of 4-haloanilines to rats induces a neurotoxicity similar in character to that evoked by the parent aniline. The decreasing order of neurotoxic potential appears to be 4-BA > 4-FA > or = 4-CA > 4-IA when comparing at or near the lethal dosage level. Copyright 2003 John Wiley & Sons, Ltd.

  20. Pharmacokinetics and Safety of a Single Oral Dose of Mirogabalin in Japanese Subjects With Varying Degrees of Renal Impairment.

    Science.gov (United States)

    Kato, Manabu; Tajima, Naoyuki; Shimizu, Takako; Sugihara, Masahiro; Furihata, Kenichi; Harada, Kazuhiro; Ishizuka, Hitoshi

    2018-01-01

    Mirogabalin (DS-5565) is a novel preferentially selective α 2 δ-1 ligand being developed for the treatment of diabetic peripheral neuropathic pain and postherpetic neuralgia. The current multicenter open-label study determined the effect of varying degrees of renal impairment on the pharmacokinetics and safety of a single dose of mirogabalin 5 mg in Japanese subjects. A total of 30 subjects (6 subjects per renal function category [normal, mild, moderate, or severe impairment; and end-stage renal disease (ESRD)]) were enrolled and completed the study. The AUC last increased with severity of renal impairment; the geometric least-squares mean ratios of AUC last compared with subjects with normal renal function were 1.3, 1.9, 3.6, and 5.3 for patients with mild, moderate, and severe impairment and ESRD, respectively. In accordance with this AUC last increase, apparent total body clearance (CL/F), renal clearance (CLr), and the cumulative percentage of mirogabalin dose excreted into urine all decreased with severity of renal impairment. There were no deaths and no severe treatment-related adverse events (TEAEs), serious TEAEs, or TEAEs resulting in study discontinuation. Mirogabalin was well tolerated in Japanese subjects with normal renal function and those with mild to severe renal impairment. It was also tolerated in subjects with ESRD but with a higher incidence of TEAEs. The most frequently reported TEAEs were dizziness (ESRD, n = 3), somnolence (ESRD, n = 2), and vomiting (ESRD, n = 2). Based on these data, a mirogabalin dose adjustment will be considered in Japanese subjects with moderate to severe renal impairment and those with ESRD. © 2017, The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.

  1. Efficacy and safety of an oral contraceptive containing ethinylestradiol 20 µg/drospirenone 3 mg (24/4 regimen) in three indications in the People's Republic of China: a comparison with international studies.

    Science.gov (United States)

    Marr, Joachim; Huang, Zirong; Wang, Baoxi; Zhang, Hongyan; Roth, Katrin

    2015-01-01

    While combined oral contraceptives are a popular choice in developed Western countries, they are used by only 1% of women who are married or in a relationship in the People's Republic of China. The purpose of this review is to describe the efficacy and safety of the combined oral contraceptive containing ethinylestradiol (EE) 20 µg/drospirenone 3 mg taken in a 24/4 regimen (YAZ ® ; Bayer HealthCare Pharmaceuticals, Berlin, Germany) by Chinese women and to compare these results with those in women assessed in the international studies. Studies of EE 20 µg/drospirenone 3 mg in three different indications (contraception, acne, and premenstrual dysphoric disorder [PMDD]) have been conducted in Chinese women. The results of these three studies indicate that the EE 20 µg/drospirenone 3 mg combined oral contraceptive is a good long-term contraceptive option in Chinese women, providing 99% contraceptive protection over the observed 1-year treatment period, and additionally had a favorable effect on moderate acne vulgaris and relieved the symptoms of PMDD. The contraceptive efficacy, improvement in acne, and relief from PMDD symptoms observed in these studies did not differ from the effects observed in other international studies of EE 20 µg/drospirenone 3 mg, indicating that EE 20 µg/drospirenone 3 mg is as effective in Chinese women as in other ethnicities. Further, EE 20 µg/drospirenone 3 mg demonstrated a similar safety and tolerability profile in women enrolled in the Chinese and international trials, with no unexpected adverse events reported in any of the three Chinese trials. Overall, the efficacy, tolerability, and degree of non-contraceptive benefits with EE 20 µg/drospirenone 3 mg appear similar in Chinese women when compared with those reported in larger studies done at other international centers.

  2. No effect of oral contraceptives on the metabolism of levetiracetam

    DEFF Research Database (Denmark)

    Sabers, Anne; Christensen, Jacob

    2011-01-01

    The effect on clearance of levetiracetam (LEV) was estimated in women with epilepsy of childbearing potential using oral contraceptives (OCs). The estimated clearance (plasma concentration/daily dose) was 39 nmol/L/mg (range 14-88 nmol/L/mg) among women who did not use OC (n=30) and 38 nmol...

  3. Acute and Subchronic Oral Toxicity Assessment of the Ethanolic ...

    African Journals Online (AJOL)

    given orally to male and female rats at doses of 250 mg/kg, 500 mg/kg and 1000 ... There were no significant differences in body weight and organ weight between ... major vital organs (liver, kidney, stomach, spleen, brain and heart) tested.

  4. A high performance liquid chromatographic assay of Mefloquine in saliva after a single oral dose in healthy adult Africans

    Directory of Open Access Journals (Sweden)

    Gbotosho Grace O

    2012-02-01

    Full Text Available Abstract Background Mefloquine-artesunate is a formulation of artemisinin based combination therapy (ACT recommended by the World Health Organization and historically the first ACT used clinically. The use of ACT demands constant monitoring of therapeutic efficacies and drug levels, in order to ensure that optimum drug exposure is achieved and detect reduced susceptibility to these drugs. Quantification of anti-malarial drugs in biological fluids other than blood would provide a more readily applicable method of therapeutic drug monitoring in developing endemic countries. Efforts in this study were devoted to the development of a simple, field applicable, non-invasive method for assay of mefloquine in saliva. Methods A high performance liquid chromatographic method with UV detection at 220 nm for assaying mefloquine in saliva was developed and validated by comparing mefloquine concentrations in saliva and plasma samples from four healthy volunteers who received single oral dose of mefloquine. Verapamil was used as internal standard. Chromatographic separation was achieved using a Hypersil ODS column. Results Extraction recoveries of mefloquine in plasma or saliva were 76-86% or 83-93% respectively. Limit of quantification of mefloquine was 20 ng/ml. Agreement between salivary and plasma mefloquine concentrations was satisfactory (r = 0.88, p Conclusion Disposition of mefloquine in saliva paralleled that in plasma, making salivary quantification of mefloquine potentially useful in therapeutic drug monitoring.

  5. Acute Oral Toxicity of Tetrodotoxin in Mice: Determination of Lethal Dose 50 (LD50 and No Observed Adverse Effect Level (NOAEL

    Directory of Open Access Journals (Sweden)

    Paula Abal

    2017-02-01

    Full Text Available Tetrodotoxin (TTX is starting to appear in molluscs from the European waters and is a hazard to seafood consumers. This toxin blocks sodium channels resulting in neuromuscular paralysis and even death. As a part of the risk assessment process leading to a safe seafood level for TTX, oral toxicity data are required. In this study, a 4-level Up and Down Procedure was designed in order to determine for the first time the oral lethal dose 50 (LD50 and the No Observed Adverse Effect Level (NOAEL in mice by using an accurate well-characterized TTX standard.

  6. Effect of two oral doses of 17beta-estradiol associated with dydrogesterone on thrombin generation in healthy menopausal women: a randomized double-blind placebo-controlled study.

    Science.gov (United States)

    Rousseau, Alexandra; Robert, Annie; Gerotziafas, Grigoris; Torchin, Dahlia; Zannad, Faiez; Lacut, Karine; Libersa, Christian; Dasque, Eric; Démolis, Jean-Louis; Elalamy, Ismail; Simon, Tabassome

    2010-04-01

    Oral hormone therapy is associated with an increased risk of venous thrombosis. Drug agencies recommend the use of the lowest efficient dose to treat menopausal symptoms for a better risk/ratio profile, although this profile has not been totally investigated yet. The aim of the study was to compare the effect of the standard dose of 17beta-estradiol to a lower one on thrombin generation (TG). In a 2-month study, healthy menopausal women were randomized to receive daily 1mg or 2 mg of 17beta-estradiol (E1, n = 24 and E2, n = 26; respectively) with 10 mg dydrogesterone or placebo (PL, n = 22). Plasma levels factors VII, X, VIII and II were assessed before and after treatment as well as Tissue factor triggered TG, which allows the investigation of the different phases of coagulation process. The peak of thrombin was higher in hormone therapy groups (E1: 42.39 +/- 50.23 nm, E2: 31.08 +/- 85.86 nm vs. 10.52 +/- 40.63 nm in PL, P = 0.002 and P = 0.01). Time to reach the peak was also shortened (PL: 0.26 +/- 0.69 min vs. E1: -0.26 +/- 0.80 min, E2: -0.55 +/- 0.79 min, P <10(-3) for both comparisons) and mean rate index of the propagation phase of TG was significantly increased. Among the studied clotting factors, only the levels of FVII were significantly increased after treatment administration. The two doses of 17beta-estradiol induced in a similar degree an acceleration of the initiation and propagation phase of tissue factor triggered thrombin generation and a significant increase of FVII coagulant activity.

  7. Pharmacokinetics of Stereoisomeric Dipeptide Prodrugs of Acyclovir Following Intravenous and Oral Administrations in Rats: A Study Involving In vivo Corneal Uptake of Acyclovir Following Oral Dosing

    Directory of Open Access Journals (Sweden)

    Ravi S.Talluri

    2009-10-01

    Full Text Available Objective: To delineate the plasma pharmacokinetics and determine the corneal uptake of valine based stereoisomeric dipeptide prodrugs of acyclovir (ACV in rats. Methods: Male Sprague-Dawley rats were used for the study. Pharmacokinetics of ACV, L-valine-acyclovir (LACV, L-valine- D-valine-acyclovir (LDACV and D-valine-L-valine acyclovir (DLACV prodrugs were delineated. These compounds were administered intravenously as a bolus via jugular vein cannula and orally by gavage. Samples were purified by protein precipitation method and analyzed by LC-MS/MS. Pertinent pharmacokinetic parameters were obtained by using WinNonlin. Corneal uptake studies of LDACV and LACV were studied following oral administration. Results: Following i.v. administration, the area under the curve (AUC in µM*min of generated ACV was in the order of LACV › LDACV › DLACV indicating their rate of metabolism. The AUC values of total drug obtained in the systemic circulation after oral administration LACV and LDACV were 1077.93 ± 236.09 and 1141.76 ± 73.67 µM*min, respectively. DLACV exhibited poor oral absorption. Cmax (µM and AUC of the intact prodrug obtained in the systemic circulation following oral administration of LDACV were almost 4–5 times higher than LACV. Moreover, concentrations achieved in the cornea after oral administration of LDACV were almost two times of LACV. Conclusions: LDACV increased both the oral bioavailability and subsequent in vivo corneal uptake of ACV. Hence, LDACV can be considered as the most promising drug candidate for delivery of ACV, in treatment of both genital herpes and ocular herpes keratitis after oral administration.

  8. Pharmacokinetics of Stereoisomeric Dipeptide Prodrugs of Acyclovir Following Intravenous and Oral Administrations in Rats: A Study Involving In vivo Corneal Uptake of Acyclovir Following Oral Dosing

    Science.gov (United States)

    Talluri, Ravi S.; Gaudana, Ripal; Hariharan, Sudharshan; Mitra, Ashim K.

    2009-01-01

    Objective To delineate the plasma pharmacokinetics and determine the corneal uptake of valine based stereoisomeric dipeptide prodrugs of acyclovir (ACV) in rats. Methods Male Sprague-Dawley rats were used for the study. Pharmacokinetics of ACV, L-valine-acyclovir (LACV), L-valine-D-valine-acyclovir (LDACV) and D-valine-L-valine acyclovir (DLACV) prodrugs were delineated. These compounds were administered intravenously as a bolus via jugular vein cannula and orally by gavage. Samples were purified by protein precipitation method and analyzed by LC-MS/MS. Pertinent pharmacokinetic parameters were obtained by using WinNonlin. Corneal uptake studies of LDACV and LACV were studied following oral administration. Results Following i.v. administration, the area under the curve (AUC) in μM*min of generated ACV was in the order of LACV > LDACV > DLACV indicating their rate of metabolism. The AUC values of total drug obtained in the systemic circulation after oral administration LACV and LDACV were 1077.93 ± 236.09 and 1141.76 ± 73.67 μM*min, respectively. DLACV exhibited poor oral absorption. Cmax (μM) and AUC of the intact prodrug obtained in the systemic circulation following oral administration of LDACV were almost 4–5 times higher than LACV. Moreover, concentrations achieved in the cornea after oral administration of LDACV were almost two times of LACV. Conclusions LDACV increased both the oral bioavailability and subsequent in vivo corneal uptake of ACV. Hence, LDACV can be considered as the most promising drug candidate for delivery of ACV, in treatment of both genital herpes and ocular herpes keratitis after oral administration. PMID:23861607

  9. Pharmacokinetics of Stereoisomeric Dipeptide Prodrugs of Acyclovir following Intravenous and Oral Administrations in Rats: A study Involving in vivo corneal Uptake of Acyclovir following Oral Dosing

    Directory of Open Access Journals (Sweden)

    Ravi S. Talluri

    2009-01-01

    Full Text Available Objective To delineate the plasma pharmacokinetics and determine the corneal uptake of valine based stereoisomeric dipeptide prodrugs of acyclovir (ACV in rats. Methods Male Sprague-Dawley rats were used for the study. Pharmacokinetics of ACV, L-valine-acyclovir (LACV, L-valine-D-valine-acyclovir (LDACV and D-valine-L-valine acyclovir (DLACV prodrugs were delineated. These compounds were administered intravenously as a bolus via jugular vein cannula and orally by gavage. Samples were purified by protein precipitation method and analyzed by LC-MS/MS. Pertinent pharmacokinetic parameters were obtained by using WinNonlin. Corneal uptake studies of LDACV and LACV were studied following oral administration. Results Following i.v. administration, the area under the curve (AUC in μM*min of generated ACV was in the order of LACV > LDACV > DLACV indicating their rate of metabolism. The AUC values of total drug obtained in the systemic circulation after oral administration LACV and LDACV were 1077.93 ± 236.09 and 1141.76 ± 73.67 μM*min, respectively. DLACV exhibited poor oral absorption. C max (μM and AUC of the intact prodrug obtained in the systemic circulation following oral administration of LDACV were almost 4–5 times higher than LACV. Moreover, concentrations achieved in the cornea after oral administration of LDACV were almost two times of LACV. Conclusions LDACV increased both the oral bioavailability and subsequent in vivo corneal uptake of ACV Hence, LDACV can be considered as the most promising drug candidate for delivery of ACV, in treatment of both genital herpes and ocular herpes keratitis after oral administration.

  10. Sublethal dose of irradiation enhances invasion of malignant glioma cells through p53-MMP 2 pathway in U87MG mouse brain tumor model

    International Nuclear Information System (INIS)

    Pei, Jian; Park, In-Ho; Ryu, Hyang-Hwa; Li, Song-Yuan; Li, Chun-Hao; Lim, Sa-Hoe; Wen, Min; Jang, Woo-Youl; Jung, Shin

    2015-01-01

    Glioblastoma is a highly lethal neoplasm that frequently recurs locally after radiotherapy, and most of these recurrences originate from near the irradiated target field. In the present study, we identified the effects of radiation on glioma invasion and p53, TIMP-2, and MMP-2 expression through in vitro and in vivo experiments. The U87MG (wt p53) and U251 (mt p53) human malignant glioma cell lines were prepared, and the U2OS (wt 53) and Saos2 (del p53) osteosarcoma cell lines were used as p53 positive and negative controls. The four cell lines and p53 knock-downed U87MG cells received radiation (2–6 Gy) and were analyzed for expression of p53 and TIMP-2 by Western blot, and MMP-2 activity was detected by zymography. In addition, the effects of irradiation on directional invasion of malignant glioma were evaluated by implanting nude mice with bioluminescent u87-Fluc in vivo followed by MMP-2, p53, and TIMP-2 immunohisto-chemistry and in situ zymography. MMP-2 activity and p53 expression increased in proportional to the radiation dose in cell lines with wt p53, but not in the cell lines with del or mt p53. TIMP-2 expression did not increase in U87MG cells. MMP-2 activity decreased in p53 knock-downed U87MG cells but increased in the control group. Furthermore, radiation enhanced MMP-2 activity and increased tumor margin invasiveness in vivo. Tumor cells invaded by radiation overexpressed MMP-2 and p53 and revealed high gelatinolytic activity compared with those of non-radiated tumor cells. Radiation-induced upregulation of p53 modulated MMP-2 activity, and the imbalance between MMP-2 and TIMP-2 may have an important role in glioblastoma invasion by degrading the extracellular matrix. Bioluminescent “U87-Fluc”was useful for observing tumor formation without sacrifice after implanting tumor cells in the mouse brain. These findings suggest that the radiotherapy involved field for malignant glioma needs to be reconsidered, and that future trials should investigate

  11. Phase 2, Randomized, Double-Blind, Dose-Ranging Study Evaluating the Safety, Tolerability, Population Pharmacokinetics, and Efficacy of Oral Torezolid Phosphate in Patients with Complicated Skin and Skin Structure Infections▿ † ‡

    Science.gov (United States)

    Prokocimer, P.; Bien, P.; Surber, J.; Mehra, P.; DeAnda, C.; Bulitta, J. B.; Corey, G. R.

    2011-01-01

    Torezolid (TR-700) is the active moiety of the prodrug torezolid phosphate ([TP] TR-701), a second-generation oxazolidinone with 4- to 16-fold greater potency than linezolid against Gram-positive species including methicillin-resistant Staphylococcus aureus (MRSA). A double-blind phase 2 study evaluated three levels (200, 300, or 400 mg) of oral, once-daily TP over 5 to 7 days for complicated skin and skin structure infections (cSSSI). Patients 18 to 75 years old with cSSSI caused by suspected or confirmed Gram-positive pathogens were randomized 1:1:1. Of 188 treated patients, 76.6% had abscesses, 17.6% had extensive cellulitis, and 5.9% had wound infections. S. aureus, the most common pathogen, was isolated in 90.3% of patients (139/154) with a baseline pathogen; 80.6% were MRSA. Cure rates in clinically evaluable patients were 98.2% at 200 mg, 94.4% at 300 mg, and 94.4% at 400 mg. Cure rates were consistent across diagnoses, regardless of lesion size or the presence of systemic signs of infection. Clinical cure rates in patients with S. aureus isolated at baseline were 96.6% overall and 96.8% for MRSA. TP was safe and well tolerated at all dose levels. No patients discontinued treatment due to an adverse event. Three-stage hierarchical population pharmacokinetic modeling yielded a geometric mean clearance of 8.28 liters/h (between-patient variability, 32.3%), a volume of the central compartment of 71.4 liters (24.0%), and a volume of the peripheral compartment of 27.9 liters (35.7%). Results of this study show a high degree of efficacy at all three dose levels without significant differences in the safety profile and support the continued evaluation of TP for the treatment of cSSSI in phase 3 trials. PMID:21115795

  12. Avaliação da tolerabilidade e do controle de ciclo de dois contraceptivos orais de baixa dose: estudo comparativo aberto Assessment of the tolerability and cycle control of two low-dose oral contraceptives: an open-label study

    Directory of Open Access Journals (Sweden)

    Edmund C. Baracat

    1998-06-01

    Full Text Available Realizou-se um estudo aberto comparativo em nove centros brasileiros para avaliar a tolerabilidade e o controle de ciclo obtido com o uso de dois contraceptivos orais de baixa dose contendo 20 mg etinilestradiol/75 mg gestodeno e 20 mg etinilestradiol/150 mg desogestrel, durante seis ciclos de tratamento. Foram selecionadas 167 mulheres saudáveis com vida sexual ativa (77 no grupo do gestodeno e 90 no grupo do desogestrel, das quais 138 completaram os seis ciclos de tratamento. Em um subgrupo de novas usuárias realizou-se também perfil lipídico e hemostático. Foram avaliados 867 ciclos no total. Ocorreu sangramento irregular em 4,6% dos ciclos com gestodeno e em 8,1% com desogestrel. A tolerabilidade a ambas preparações foi boa, mas houve significativamente mais náusea no grupo do desogestrel. O controle de ciclo foi bom com os dois contraceptivos, sendo que houve freqüência significativamente menor de sangramento irregular no grupo do gestodeno quando se leva em conta que todos os ciclos foram considerados. Não houve alterações clinicamente significativas no perfil hemostático. O perfil lipídico mostrou tendência a tornar-se mais favorável após seis ciclos de tratamento com as duas preparações. Não ocorreu alteração no peso médio das mulheres no grupo do gestodeno; no grupo do desogestrel houve aumento significativo no peso médio de aproximadamente 1 kg após seis meses de tratamento. A adesão ao tratamento foi boa com as duas preparações. Os resultados deste estudo mostram que preparações contendo baixa dose de gestodeno ou desogestrel associados a 20 mg de etinilestradiol são contraceptivos bem tolerados que permitem bom controle de ciclo, sem efeitos colaterais significantes.An open-label comparative study was conducted in nine centers in Brazil to evaluate the tolerability and cycle control of two low-dose oral contraceptives containing 20 mg ethynylestradiol/75 mg gestodene and 20 mg ethynylestradiol/150 mg

  13. Efficacy and safety of premedication with single dose of oral pregabalin in children with dental anxiety: A randomized double-blind placebo-controlled crossover clinical trial

    Directory of Open Access Journals (Sweden)

    Tahereh Eskandarian

    2015-01-01

    Full Text Available Background: Dental anxiety is a relatively frequent problem that can lead to more serious problems such as a child entering a vicious cycle as he/she becomes reluctant to accept the required dental treatments. The aim of this randomized double-blind clinical trial study was to evaluate the anxiolytic and sedative effect of pregabalin in children. Materials and Methods: Twenty-five children were randomized to a double-blind placebo-controlled crossover clinical trial. Two visits were scheduled for each patient. At the first visit, 75 mg pregabalin or placebo was given randomly, and the alternative was administered at the next visit. Anxiolytic and sedative effects were measured using the visual analogue scale. The child′s behavior was rated with the Frankl behavioral rating scale and the sedation level during the dental procedure was scored using the Ramsay sedation scale. The unpaired, two-tailed Student′s t-test was used to compare the mean changes of visual analog scale (VAS for anxiety in the pregabalin group with that of the placebo group. A repeated measures MANOVA model was used to detect differences in sedation level in the pregabalin and placebo groups regarding the interaction of 3-time measurements; sub-group analysis was performed using Student′s t-test. The Mann-Whitney U-test was used to analyze the nonparametric data of the Frankl and Ramsay scales. A P < 0.05 was considered significant. Results: The reduction of the VAS-anxiety score from 2 h post-dose was statistically significant in the pregabalin group. From 2 h to 4 h post-dose, the VAS-sedation score increased significantly in the pregabalin group. The child′s behavior rating was not significantly different between the groups. The number of "successful" treatment visits was higher in the pregabalin group compared to the placebo group. Conclusion: Significant anxiolytic and sedative effects can be anticipated 2 h after oral administration of pregabalin without serious

  14. Bioavailability of diclofenac potassium at low doses

    Science.gov (United States)

    Hinz, Burkhard; Chevts, Julia; Renner, Bertold; Wuttke, Henrike; Rau, Thomas; Schmidt, Andreas; Szelenyi, Istvan; Brune, Kay; Werner, Ulrike

    2005-01-01

    Aim Diclofenac-K has been recently launched at low oral doses in different countries for over-the-counter use. However, given the considerable first-pass metabolism of diclofenac, the degree of absorption of diclofenac-K at low doses remained to be determined. The aim of this study was to determine the bioavailability of low-dose diclofenac-K. Methods A randomized, three-way, cross-over study was performed in 10 subjects. Each received diclofenac-K, 22.5 mg via short-term i.v. infusion and orally at single doses of 12.5 mg and 25 mg. Results Mean (± SD) times to maximal plasma concentration (tmax) of diclofenac were 0.48 ± 0.28 h (12.5 mg) and 0.93 ± 0.96 h (25 mg). The absolute bioavailability of diclofenac-K after oral administration did not differ significantly in the 12.5-mg and 25-mg dose group (63.1 ± 12.6% vs. 65.1 ± 19.4%, respectively). The 90% confidence intervals for the AUC∞ and AUCt ratios for the two oral regimes were 82.6, 103.4% (point estimate 92.4%) and 86.2, 112.9% (point estimate 98.6%), respectively. These values were within the acceptance criteria for bioequivalence (80–125%). Conclusions Our data indicate that diclofenac-K is rapidly and well absorbed at low dose, and are consistent with a rapid onset of action of the drug. Abbreviations AUC, area under plasma concentraton-time curve; Cmax, peak plasma concentration; CI, confidence interval; COX, cyclooxygenase; D, dose; F, absolute bioavailability; tmax, time to reach Cmax. PMID:15606444

  15. Determination of uranium content in dental porcelains by means of the fission track method and estimation of radiation dose to oral mucosa by radioactive elements

    International Nuclear Information System (INIS)

    Sairenji, E.; Moriwaki, K.; Shimizu, M.; Noguchi, K.

    1980-01-01

    Porcelain teeth, some of which contain uranium compounds for aesthetic purpose, have been widely used in dental clinics. Hazardous effects due to uranium radiation have been suggested in recent publications. In the present study uranium concentrations were determined in four major brands of porcelain teeth marketed in Japan using the fission track method, and the absorbed doses to oral tissued were calculated. Average uranium concentrations of the brands studied were determined to be 3.6 ppm (0.33-10 ppm, Japan), 18 ppm (0.69-81 ppm, Japan), 9.4 ppm (2.5-14 ppm, Japan) and 82 ppm (11-205 ppm, U.S.), respectively. The corresponding dose equivalents at the surface of oral mucosal membrane were 2.9 rem yr -1 . 14 rem yr -1 , 7.6 rem yr -1 and 66 rem yr -1 . (author)

  16. Determination of uranium content in dental porcelains by means of the fission track method and estimation of radiation dose to oral mucosa by radioactive elements

    International Nuclear Information System (INIS)

    Sairenji, Eiko; Moriwaki, Kazunari; Shimizu, Masami; Noguchi, Kunikazu; Anzai, Ikuro.

    1979-01-01

    Porcelain teeth, some of which contained uranium compounds for aesthetic purpose, have been widely used in dental clinics. Recently, the hazardous effects by uranium radiation were suggested. In the present study, the authors carried out the determination of uranium concentrations of four major brands of porcelain teeth marketed in Japan using the fission track method, and the absorbed doses of oral tissues were calculated by the authors' introduced formula for calculation of alpha radiation. Average uranium concentrations of the brands studied were determined 3.6 ppm (0.33 - 10 ppm, Japan), 18 ppm (0.69 - 81 ppm, Japan), 9.4 ppm (2.5 - 14 ppm, Japan) and 82 ppm (11 - 205 ppm, U.S.A.), respectively. The corresponding dose equivalents at the surface of oral mucosal membrane were 2.9 rem y -1 , 14 rem y -1 , 7.6 rem y -1 and 66 rem y -1 . (author)

  17. Desarrollo de la formulación de la suspensión oral de ibuprofeno 100 mg/5 mL para uso pediátrico Development of formulation for oral suspension Ibuprofen 100 mg/5mL for pediatric use

    Directory of Open Access Journals (Sweden)

    Nilia de la Paz Martín-Viaña

    2009-08-01

    Full Text Available Se empleó el método de prueba y error para el desarrollo de la formulación de la suspensión oral de ibuprofeno 100 mg/5 mL para uso pediátrico; se estudió su estabilidad químico-física por el método acelerado y de vida de estante; se envasó en frasco de vidrio ámbar por 120 mL y se almacenó a temperatura ambiente. Se realizó el estudio reológico y la determinación de la viscosidad aparente, además, se efectuó el estudio microbiológico a través de la prueba de efectividad de preservativo antimicrobiano y el conteo microbiano; se comprobó la seguridad del producto mediante el estudio toxicológico. Todos los resultados cumplieron con los límites de calidad establecidos en la literatura científica, USP 30, para este tipo de forma farmacéutica. Se concluye que el medicamento desarrollado está correctamente formulado, desde el punto de vista galénico con un tiempo de vida útil de 24 meses bajo las condiciones estudiadas.Authors used the test and error method to develop the formulation of Ibuprofen oral suspension (100 mg/5 mL for pediatric use. Its chemical-physic stability was studied through accelerated method and shelf life. It was bottled in amber glass small bottles by 120 mL, and it was stored at room temperature. A rheology study and assessment of apparent viscosity was made as well as a microbiologic one by test of effectiveness of antimicrobial preservative and the microbial count. Product safe was verified by toxicology study. All results fulfilled quality limits established in scientific literature, USP 30, for this type of pharmaceutical method. We conclude that drug developed is correctly formulated, from the doctoral point of view with a time of useful life of 24 months under study conditions.

  18. Text mining-based in silico drug discovery in oral mucositis caused by high-dose cancer therapy.

    Science.gov (United States)

    Kirk, Jon; Shah, Nirav; Noll, Braxton; Stevens, Craig B; Lawler, Marshall; Mougeot, Farah B; Mougeot, Jean-Luc C

    2018-08-01

    Oral mucositis (OM) is a major dose-limiting side effect of chemotherapy and radiation used in cancer treatment. Due to the complex nature of OM, currently available drug-based treatments are of limited efficacy. Our objectives were (i) to determine genes and molecular pathways associated with OM and wound healing using computational tools and publicly available data and (ii) to identify drugs formulated for topical use targeting the relevant OM molecular pathways. OM and wound healing-associated genes were determined by text mining, and the intersection of the two gene sets was selected for gene ontology analysis using the GeneCodis program. Protein interaction network analysis was performed using STRING-db. Enriched gene sets belonging to the identified pathways were queried against the Drug-Gene Interaction database to find drug candidates for topical use in OM. Our analysis identified 447 genes common to both the "OM" and "wound healing" text mining concepts. Gene enrichment analysis yielded 20 genes representing six pathways and targetable by a total of 32 drugs which could possibly be formulated for topical application. A manual search on ClinicalTrials.gov confirmed no relevant pathway/drug candidate had been overlooked. Twenty-five of the 32 drugs can directly affect the PTGS2 (COX-2) pathway, the pathway that has been targeted in previous clinical trials with limited success. Drug discovery using in silico text mining and pathway analysis tools can facilitate the identification of existing drugs that have the potential of topical administration to improve OM treatment.

  19. Short-term response of bone turnover to low-dose oral contraceptives in exercising women with hypothalamic amenorrhea.

    Science.gov (United States)

    Vescovi, Jason D; VanHeest, Jaci L; De Souza, Mary Jane

    2008-02-01

    We examined the response of bone turnover markers and indices of energy status after 2 weeks of oral contraceptive (OC) therapy in premenopausal women with exercise-associated menstrual disturbances (EAMD). Six women with EAMD received one 28-day cycle of a triphasic OC containing 180-250 mcg norgestimate/25 mcg ethinyl estradiol (EAMD+OC) and six were controls (EAMD controls). Bone turnover markers amino-terminal propeptide of Type I procollagen and serum carboxy-terminal telopeptides of Type I collagen (PINP and SCTX-I) were assessed at baseline and after 2 weeks of OC therapy (EAMD+OC) or after a 30-day monitoring period (EAMD controls). Total triiodothyronine, resting energy expenditure (REE) and dietary intake were assessed as secondary end points. The absolute and percent changes from baseline in the primary and secondary outcomes were evaluated using an analysis of covariance, adjusting for baseline values of the corresponding outcome. Compared to EAMD controls, a significant change from baseline was observed in the EAMD+OC group for PINP (mean+/-SEM, 9.9+/-6.1 vs. -33.9+/-9.0 mcg/L; p=.005) and SCTX-I (-0.02+/-0.11 vs. -0.25+/-0.07 ng/mL; p=.017), but not osteoprotegerin (-0.53+/-0.22 vs. 0.20+/-0.44 pmol/L; p=.429) after 2 weeks (14.7+/-0.3 days) of OC therapy. Total triiodothyronine levels were elevated in the EAMD+OC group after therapy compared with EAMD controls (19.7+/-4.1 vs. -8.4+/-4.9 ng/dL; p=.002); however, no differences between groups were observed for the changes in REE or dietary intake. Our data demonstrate that 2 weeks of low-dose OC therapy rapidly reduced markers of bone resorption and formation, without any significant impact on energy status in women with EAMD.

  20. Effect of high-dose oral multivitamins and minerals in participants not treated with statins in the randomized Trial to Assess Chelation Therapy (TACT).

    Science.gov (United States)

    Issa, Omar M; Roberts, Rhonda; Mark, Daniel B; Boineau, Robin; Goertz, Christine; Rosenberg, Yves; Lewis, Eldrin F; Guarneri, Erminia; Drisko, Jeanne; Magaziner, Allan; Lee, Kerry L; Lamas, Gervasio A

    2018-01-01

    In a prespecified subgroup analysis of participants not on statin therapy at baseline in the TACT, a high-dose complex oral multivitamins and multimineral regimen was found to have a large unexpected benefit compared with placebo. The regimen tested was substantially different from any vitamin regimen tested in prior clinical trials. To explore these results, we performed detailed additional analyses of participants not on statins at enrollment in TACT. TACT was a factorial trial testing chelation treatments and a 28-component high-dose oral multivitamins and multiminerals regimen versus placebo in post-myocardial infarction (MI) patients 50 years or older. There were 460 (27%) of 1,708 TACT participants not taking statins at baseline, 224 (49%) were in the active vitamin group and 236 (51%) were in the placebo group. Patients were enrolled at 134 sites around the United States and Canada. Daily high-dose oral multivitamins and multiminerals (6 tablets, active or placebo). The primary end point of TACT was time to the first occurrence of any component of the composite end point: all-cause mortality, MI, stroke, coronary revascularization, or hospitalization for angina. The primary end point occurred in 137 nonstatin participants (30%), of which 51 (23%) of 224 were in the active group and 86 (36%) of 236 were taking placebo (hazard ratio, 0.62; 95% confidence interval, 0.44-0.87; P=.006). Results in the key TACT secondary end point, a combination of cardiovascular mortality, stroke, or recurrent MI, was consistent in favoring the active vitamin group (hazard ratio, 0.46; 95% confidence interval, 0.28-0.75; P=.002). Multiple end point analyses were consistent with these results. High-dose oral multivitamin and multimineral supplementation seem to decrease combined cardiac events in a stable, post-MI population not taking statin therapy at baseline. These unexpected findings are being retested in the ongoing TACT2. Copyright © 2017 The Authors. Published by Elsevier

  1. Determination of Effect of Low Dose Vs Moderate Dose of Clofibrate on the Decreasing in Serum Bilirubin Level in the Term Healthy Neonate

    OpenAIRE

    Mohammad Ashkan Moslehi; Narges Pishva

    2007-01-01

    Objective: This study was performed to determine the effect of low doses (25 mg/Kg) vs. moderate doses (50 mg/Kg) of clofibrate in treatment of non-hemolytic hyperbilirubin¬emia in healthy term neonates. Material & Methods: A clinical randomized controlled trial was performed in three groups of healthy term neonates. One group was treated with a single low dose of clofibrate (25 mg/Kg) while another group received a single moderate dose (50mg/kg) both orally plus phototherapy; the results wer...

  2. Absorption, distribution, metabolism and excretion of selenium following oral administration of elemental selenium nanoparticles or selenite in rats

    DEFF Research Database (Denmark)

    Löschner, Katrin; Hadrup, Niels; Hansen, Marianne

    2014-01-01

    A suspension of nanoparticles of BSA-stabilized red amorphous elemental selenium (Se) or an aqueous solution of sodium selenite was repeatedly administered by oral gavage for 28 days at 0.05 mg/kg bw/day (low dose) or at 0.5 mg/kg bw/day (high dose) as Se to female rats. Prior to administration...

  3. Steady-State Serum T3 Concentrations for 48 Hours Following the Oral Administration of a Single Dose of 3,5,3'-Triiodothyronine Sulfate (T3S).

    Science.gov (United States)

    Santini, Ferruccio; Giannetti, Monica; Ricco, Ilaria; Querci, Giorgia; Saponati, Giorgio; Bokor, Daniela; Rivolta, Giovanni; Bussi, Simona; Braverman, Lewis E; Vitti, Paolo; Pinchera, Aldo

    2014-07-01

    Sulfate conjugation of thyroid hormones is an alternate metabolic pathway that facilitates the biliary and urinary excretion of iodothyronines and enhances their deiodination rate, leading to the generation of inactive metabolites. A desulfating pathway reverses this process, and thyromimetic effects have been observed following the parenteral administration of 3,5,3'-triiodothyronine (T3) sulfate (T3S) in rats. The present study investigated whether T3S is absorbed after oral administration in humans and if it represents a source of T3. Twenty-eight hypothyroid patients (7 men and 21 women; mean age, 44 ± 11 years) who had a thyroidectomy for thyroid carcinoma were enrolled. Replacement thyroid hormone therapy was withdrawn (42 days for thyroxine, 14 days for T3) prior to 131I remnant ablation. A single oral dose of 20, 40, 80 (4 patients/group), or 160 μg (16 patients/group) of T3S was administered 3 days before the planned administration of 131I. Blood samples for serum T3S and total T3 (TT3) concentrations were obtained at various times up to 48 hours after T3S administration. At all T3S doses, serum T3S concentrations increased, reaching a peak at 2 to 4 hours and progressively returning to basal levels within 8 to 24 hours. The T3S maximum concentration (Cmax) and area under the 0- to 48-hour concentration-time curve (AUC0-48h) were directly and significantly related to the administered dose. An increase in serum TT3 concentration was observed (significant after 1 hour), and the concentration increased further at 2 and 4 hours and then remained steady up to 48 hours after T3S administration. There was a significant direct correlation between the TT3 AUC0-48h and the administered dose of T3S. No changes in serum free thyroxine (T4) concentrations during the entire study period were observed, whereas serum thyroid-stimulating hormone levels increased slightly at 48 hours, but this was not related to the dose of T3S. No adverse events were reported. (1) T3S is

  4. Evaluation of the Risk of Grade 3 Oral and Pharyngeal Dysphagia Using Atlas-Based Method and Multivariate Analyses of Individual Patient Dose Distributions

    Energy Technology Data Exchange (ETDEWEB)

    Otter, Sophie [Department of Clinical Oncology, Royal Marsden Hospital, Sutton and London (United Kingdom); Schick, Ulrike; Gulliford, Sarah [Department of Clinical Oncology, Royal Marsden Hospital, Sutton and London (United Kingdom); The Institute of Cancer Research, London (United Kingdom); Lal, Punita [Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow India (India); Franceschini, Davide [Department of Radiotherapy and Radiosurgery, Humanitas Research Hospital, Milan (Italy); Newbold, Katie; Nutting, Christopher; Harrington, Kevin [Department of Clinical Oncology, Royal Marsden Hospital, Sutton and London (United Kingdom); The Institute of Cancer Research, London (United Kingdom); Bhide, Shreerang, E-mail: shreerang.bhide@icr.ac.uk [Department of Clinical Oncology, Royal Marsden Hospital, Sutton and London (United Kingdom); The Institute of Cancer Research, London (United Kingdom); Department of Radiotherapy and Radiosurgery, Humanitas Research Hospital, Milan (Italy)

    2015-11-01

    Purpose: The study aimed to apply the atlas of complication incidence (ACI) method to patients receiving radical treatment for head and neck squamous cell carcinomas (HNSCC), to generate constraints based on dose-volume histograms (DVHs), and to identify clinical and dosimetric parameters that predict the risk of grade 3 oral mucositis (g3OM) and pharyngeal dysphagia (g3PD). Methods and Materials: Oral and pharyngeal mucosal DVHs were generated for 253 patients who received radiation (RT) or chemoradiation (CRT). They were used to produce ACI for g3OM and g3PD. Multivariate analysis (MVA) of the effect of dosimetry, clinical, and patient-related variables was performed using logistic regression and bootstrapping. Receiver operating curve (ROC) analysis was also performed, and the Youden index was used to find volume constraints that discriminated between volumes that predicted for toxicity. Results: We derived statistically significant dose-volume constraints for g3OM over the range v28 to v70. Only 3 statistically significant constraints were derived for g3PD v67, v68, and v69. On MVA, mean dose to the oral mucosa predicted for g3OM and concomitant chemotherapy and mean dose to the inferior constrictor (IC) predicted for g3PD. Conclusions: We have used the ACI method to evaluate incidences of g3OM and g3PD and ROC analysis to generate constraints to predict g3OM and g3PD derived from entire individual patient DVHs. On MVA, the strongest predictors were radiation dose (for g3OM) and concomitant chemotherapy (for g3PD).

  5. A prospective pilot study on the effect of sucralfate mouth-swishing in reducing stomatitis during radiotherapy of the oral cavity

    International Nuclear Information System (INIS)

    Pfeiffer, P.; Hansen, O.; Madsen, E.L.; May, O.

    1990-01-01

    Radiotherapy in sufficient dose involving the oral cavity always causes stomatitis, the severity of which is dependent on primary diagnosis, age, oral status and whether concomitant chemotherapy is given or not. The aim of the present pilot study was to assess whether mouth-swishing with sucralfate suspension might reduce oral radiation mucositis without disturbing side effects. (orig./MG)

  6. A prospective pilot study on the effect of sucralfate mouth-swishing in reducing stomatitis during radiotherapy of the oral cavity

    Energy Technology Data Exchange (ETDEWEB)

    Pfeiffer, P.; Hansen, O.; Madsen, E.L.; May, O. (Odense Univ. (Denmark). Dept. of Oncology)

    1990-01-01

    Radiotherapy in sufficient dose involving the oral cavity always causes stomatitis, the severity of which is dependent on primary diagnosis, age, oral status and whether concomitant chemotherapy is given or not. The aim of the present pilot study was to assess whether mouth-swishing with sucralfate suspension might reduce oral radiation mucositis without disturbing side effects. (orig./MG).

  7. Low-dose oral contraceptives and acquired resistance to activated protein C: a randomised cross-over study

    NARCIS (Netherlands)

    Rosing, J.; Middeldorp, S.; Curvers, J.; Christella, M.; Thomassen, L. G.; Nicolaes, G. A.; Meijers, J. C.; Bouma, B. N.; Büller, H. R.; Prins, M. H.; Tans, G.

    1999-01-01

    BACKGROUND: We have reported previously that, compared with use of second-generation oral contraceptives, the use of third-generation oral contraceptives is associated with increased resistance to the anticoagulant action of activated protein C (APC). Owing to the cross-sectional design of that

  8. Oral fluconazole in tinea versicolor

    Directory of Open Access Journals (Sweden)

    Sankara Rao I

    1997-01-01

    Full Text Available 25 patients with extensive tinea versicolor were treated with single oral dose of 400 mg of fluconazole. 25 patients returned for follow-up. Follow-up at 3 weeks, 6 weeks and 8 weeks showed 100% clinical cure rate and 92% mycological cure rate. No significant side effects were noticed. The majority of patients found the treatment effective, safe and convenient.

  9. SINGLE-DOSE VERSUS 3-DAY PROPHYLAXIS WITH CIPROFLOXACIN IN TRANSURETHRAL SURGERY - A CLINICAL-TRIAL

    NARCIS (Netherlands)

    BIJL, W; JANKNEGT, RA

    1993-01-01

    in 235 patients who underwent transurethral surgery, perioperative oral ciprofloxacin prophylaxis was given as a single dose 500 mg versus a 3-day regimen. Out of 180 evaluable patients, 84 received a single dose and 96 received a 3-day course. In the single dose prophylaxis group there were 5

  10. Effect of single oral doses of sitagliptin, a dipeptidyl peptidase-4 inhibitor, on incretin and plasma glucose levels after an oral glucose tolerance test in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Herman, Gary A; Bergman, Arthur; Stevens, Catherine

    2006-01-01

    CONTEXT: In response to a meal, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) are released and modulate glycemic control. Normally these incretins are rapidly degraded by dipeptidyl peptidase-4 (DPP-4). DPP-4 inhibitors are a novel class of oral antihyperglyce......CONTEXT: In response to a meal, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) are released and modulate glycemic control. Normally these incretins are rapidly degraded by dipeptidyl peptidase-4 (DPP-4). DPP-4 inhibitors are a novel class of oral...... antihyperglycemic agents in development for the treatment of type 2 diabetes. The degree of DPP-4 inhibition and the level of active incretin augmentation required for glucose lowering efficacy after an oral glucose tolerance test (OGTT) were evaluated. OBJECTIVE: The objective of the study was to examine...... concentrations; and sitagliptin pharmacokinetics. RESULTS: Sitagliptin dose-dependently inhibited plasma DPP-4 activity over 24 h, enhanced active GLP-1 and GIP levels, increased insulin/C-peptide, decreased glucagon, and reduced glycemic excursion after OGTTs administered at 2 and 24 h after single oral 25...

  11. Comparison of the Effect of Pre-operative Single Oral Dose of Tramadol and Famotidine on Gastric Secretions pH and Volume in Patients Scheduled for Laparoscopic Cholecystectomy

    International Nuclear Information System (INIS)

    Khan, M. U.; Aqil, M.; Hussain, A.; Zahrani, T. A.; Hillis, M.

    2015-01-01

    Objective: To evaluate and compare the effects of pre-operative single oral dose of tramadol and famotidine on gastric secretions pH and volume in patients electively scheduled for laparoscopic cholecystectomy. Study Design: Randomized control trial. Place and Duration of Study: Department of Anaesthesia, King Saud University Riyadh, Saudi Arabia, from August 2011 to June 2013. Methodology: Ninety adult, ASA-I and II patients scheduled for laparoscopic cholecystectomy were included in the study. Patients were randomly assigned to receive pre-operatively either placebo (Group-C, n=30), oral tramadol 100 mg (Group-T, n=30) or famotidine 40 mg (Group-F, n=30). After induction of general anaesthesia, gastric fluid was aspirated through orogastric tube. The gastric secretions volume and pH was measured using pH meter. Results:There was no statistically difference between groups in age, weight and gender. The gastric secretions mean pH was 2.06 ± 0.22,2.04 ± 0.20, 5.79 ± 0.77 and volume was 0.59 ± 0.17, 0.59 ± 0.14 and 0.28 ± 0.16 ml/kg in Group-C, Group-T and Group-F respectively. There was a significant statistical difference in the mean pH values between Group-C vs. Group-F (p greater than 0.001) and Group-Tvs. Group-F (p greater than 0.001). Statistically significant difference was also found in the mean gastric secretions volume between Group - C vs. Group-F (p greater than 0.001) and Group-Tvs. Group-F (p greater than 0.001). There was no significant difference in the mean gastric fluid pH values (p=0.99) and mean gastric secretions volume (p=0.99) between Group-Tand Group-C. Conclusion:As compared to famotidine, pre-operative single oral dose of tramadol was unable to elevate the desired level of gastric fluid pH (less than 2.5) and decrease in gastric secretions volume (greater than 0.4ml/kg). (author)

  12. Clinical and microbiological outcomes in treatment of men with non-gonococcal urethritis with a 100-mg twice-daily dose regimen of sitafloxacin.

    Science.gov (United States)

    Ito, Shin; Yasuda, Mitsuru; Seike, Kensaku; Sugawara, Takashi; Tsuchiya, Tomohiro; Yokoi, Shigeaki; Nakano, Masahiro; Deguchi, Takashi

    2012-06-01

    Several microorganisms cause non-gonococcal urethritis (NGU). Failure to eradicate Mycoplasma genitalium from the urethra could be associated with persistent or recurrent urethritis; thus, the choice of antibiotics with activities potent enough to eradicate M. genitalium is crucial in the treatment of NGU. In in vitro studies, sitafloxacin has been shown to be highly active against Chlamydia trachomatis and M. genitalium. We treated 89 males with NGU, including 15 patients with persistent or recurrent NGU and 1 patient with post-gonococcal urethritis, with a 100-mg twice-daily dose regimen of sitafloxacin to assess its efficacy against NGU. We examined first-void urine samples for the presence of C. trachomatis, M. genitalium, Ureaplasma parvum, and Ureaplasma urealyticum. After treatment, we evaluated 73 patients for clinical outcomes and 44 for microbiological outcomes. Symptoms were alleviated in 62 (84.9%) patients, who were judged clinically cured. Microorganisms detected before treatment were eradicated in 42 (95.5%) patients, who were judged microbiologically cured. Regarding microbiological outcomes of specific microorganisms, eradication rates of C. trachomatis (n = 33), M. genitalium (n = 11), and U. urealyticum (n = 10) were 100%, 100%, and 80.0%, respectively. In all 5 patients with M. genitalium-positive persistent or recurrent NGU who had experienced treatment failures with antibiotics, the mycoplasma was eradicated. These results suggested that the sitafloxacin regimen used, which was effective on both M. genitalium and C. trachomatis infections, could be useful as an appropriate option as first- and second-line treatment of NGU.

  13. Evaluation of the efficacy of palliative irradiation with high fractionated doses and planned intervals of patients with advanced cancer of the oral cavity and pharynx

    International Nuclear Information System (INIS)

    Skolyszewski, J.; Reinfuss, M.

    1988-01-01

    200 patients, previously not treated, with advanced highly differentiated cancer of the oral cavity and pharynx have been palliatively irradiated in the Oncology Center in Cracow in the years 1976-1985. Megavoltage irradiation with fractionated doses 4-5 Gy up to the dose of 20 Gy to the tumor with 4-5 fractions during 4-7 days has been applied. 64 patients received 20 Gy as simple dose, in 65 cases such dose has been repeated after month. 71 patients have been irradiated for the third time with similar dose after another 1 month interval. Partial regression of 25-50% of the tumor volume has been obtained after the first series of irradiation in 19% of patients and more than 50% in 28% of patients, complete regression in 4% of patients. 15,5% of the total number of patients survived 1 year since the initiation of the irradiation, 5% without symptoms of the neoplasm. Worse prognosis is connected with major advancement of the tumor (T 4 , N 2 ), poor general condition, cachexia and alcohol addition. Absence of improvement after the first series of irradiations indicates the non-effectiveness of the treatment. Palliative treatment by irradiation with high fractionated doses and planned interval is a safe and efficacious method. 1 fig., 6 tabs., 14 refs. (author)

  14. Iron prophylaxis during pregnancy -- how much iron is needed? A randomized dose- response study of 20-80 mg ferrous iron daily in pregnant women

    DEFF Research Database (Denmark)

    Milman, Nils; Bergholt, Thomas; Eriksen, Lisbeth

    2005-01-01

    To determine the lowest dose of iron preventative of iron deficiency and iron deficiency anemia in pregnancy.......To determine the lowest dose of iron preventative of iron deficiency and iron deficiency anemia in pregnancy....

  15. An oral sensitization model in Brown Norway rats to screen for potential allergenicity of food proteins

    NARCIS (Netherlands)

    Knippels, L.M.J.; Houben, G.F.; Spanhaak, S.; Penninks, A.H.

    1999-01-01

    We developed an oral sensitization protocol for food proteins for the rat. Young Brown Norway (BN) rats were exposed to 1 mg ovalbumin (OVA) by daily gavage dosing for 42 days without the use of an adjuvant. OVA-specific IgE and IgG responses were determined by ELISA. On an oral challenge with OVA

  16. Oral metiamide as an effective inhibitor of gastric acid secretion in man

    African Journals Online (AJOL)

    A method is described for the evaluation of the effect of oral therapy on gastric acid secretion. Metiamide, a histamine H2-receptor antagonist, produced a 51% inhibition of pentagastrin-stimulated gastric acid secretion during the third hour after a standard 200-mg oral dose in man. S. Afr. Med. J., 48, 2018 (1974).

  17. Thallium-201 myocardial imaging during pharmacologic coronary vasodilation: comparison of oral and intravenous administration of dipyridamole

    International Nuclear Information System (INIS)

    Taillefer, R.; Lette, J.; Phaneuf, D.C.; Leveille, J.; Lemire, F.; Essiambre, R.

    1986-01-01

    Although the diagnostic utility of thallium-201 myocardial imaging after dipyridamole infusion is well established, the intravenous form of the drug is not yet commercially available in North America. Fifty patients referred for coronary angiography were prospectively studied. Within a 2 week period, each patient underwent cardiac catheterization and thallium-201 myocardial imaging after both oral and intravenous dipyridamole administration. For the oral protocol, patients were randomly assigned to treatment with either 200 or 400 mg of dipyridamole in tablet form. Coronary artery stenoses of 70% or greater were considered significant. For the 25 patients who received a 200 mg oral dose of dipyridamole, the scintigraphic study showed perfusion defects in 65% of patients with significant coronary artery disease after the oral dose and in 85% of patients after the intravenous dose. For the 25 patients who received a 400 mg oral dose, the sensitivity of the scintigram was 84% after the oral dose and 79% after the intravenous dose. Except for headache and nausea, side effects were less severe and less frequent with oral (either 200 or 400 mg) than with intravenous dipyridamole. Because of the delayed and variable absorption of dipyridamole tablets, the oral studies required a longer period of medical supervision (45 to 60 minutes), and aminophylline was empirically administered after completion of the first set of thallium-201 imag