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Sample records for once-daily mmx mesalamine

  1. Patient considerations in the management of ulcerative colitis: role of once-daily MMX mesalamine

    Directory of Open Access Journals (Sweden)

    Daniel B Zandman

    2009-03-01

    Full Text Available Daniel B Zandman, Mark A PeppercornHarvard Medical School, Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USAAbstract: Mesalamine and its derivatives are effective and well-tolerated therapies for ulcerative colitis. However, patient adherence to traditional mesalamine-based therapy is poor, and is often limited by heavy pill burdens and frequent dosing intervals. This can lead to ineffective disease control, impaired quality of life, and preventable morbidity and mortality. Previous studies have suggested that a once-daily mesalamine regimen would be strongly adhered to in the outpatient setting, but at that time no such formulation of mesalamine existed. In 2007, clinical trial data showed a novel, once-daily, multi-matrix (MMX formulation of mesalamine to be effective in both remission induction and remission maintenance. This breakthrough in drug delivery allowed the unification of an effective therapeutic with a formulation that enables outpatients to be increasingly adherent to their medication. In theory, this might result in improved outpatient disease control and a decreased number of flares. As the use of MMX mesalamine increases, studies examining the outpatient community adherence rate need to be performed.Keywords: mesalamine, MMX, Lialda™, ulcerative colitis, inflammatory bowel disease, adherence

  2. Once-daily mesalamine granules for ulcerative colitis.

    Science.gov (United States)

    Lawlor, Garrett; Ahmed, Awais; Moss, Alan C

    2010-07-01

    Mesalamine extended-release capsules (Apriso [Salix Pharmaceuticals, Raleigh, NC, USA]) are the first once-daily mesalamine preparation approved by the US FDA for the maintenance of remission of ulcerative colitis (UC). Each mesalamine extended-release capsule contains granules of a mesalamine-polymer matrix that are coated with a pH-sensitive resin. This design begins releasing mesalamine (0.375 g) once the pH is more than 6 in the ileum and colon. Two clinical trials have reported that mesalamine extended-release capsules (1.5 g/day) maintained remission in 79% of patients with UC who were in clinical remission. Reported adherence with mesalamine extended-release capsules once daily was high (>90%) in these studies. This article examines the efficacy and safety of mesalamine extended-release capsules in the maintenance of remission in patients with UC.

  3. Maintaining remission in ulcerative colitis--role of once daily extended-release mesalamine.

    Science.gov (United States)

    Oliveira, Lilliana; Cohen, Russell D

    2011-02-27

    The aminosalicylates (5-ASA; also referred to as mesalamine-based agents) are considered as first-line in the maintenance of remission of mild to moderate ulcerative colitis (UC). Traditionally these agents have required a large pill burden and multiple daily dosing regimens which may account for the low adherence rates, especially in patients in remission. Extended-release mesalamine is the first once daily mesalamine product approved by the Food and Drug Administration for the maintenance of UC remission. This review will examine the pharmacokinetics, dosing, efficacy, and safety data of extended-release mesalamine, and discuss the potential role of improving medication compliance and decreasing costs in UC maintenance.

  4. Maintaining remission in ulcerative colitis – role of once daily extended-release mesalamine

    Directory of Open Access Journals (Sweden)

    Lilliana Oliveira

    2011-02-01

    Full Text Available Lilliana Oliveira, Russell D CohenThe Department of Medicine, Section of Gastroenterology, University of Chicago Medical Center, Chicago, IL, USAAbstract: The aminosalicylates (5-ASA; also referred to as mesalamine-based agents are considered as first-line in the maintenance of remission of mild to moderate ulcerative colitis (UC. Traditionally these agents have required a large pill burden and multiple daily dosing regimens which may account for the low adherence rates, especially in patients in remission. Extended-release mesalamine is the first once daily mesalamine product approved by the Food and Drug Administration for the maintenance of UC remission. This review will examine the pharmacokinetics, dosing, efficacy, and safety data of extended-release mesalamine, and discuss the potential role of improving medication compliance and decreasing costs in UC maintenance.Keywords: ulcerative colitis, 5-ASA, mesalamine, adherence, compliance, quality of life, costs

  5. Clinical trial: a novel high-dose 1 g mesalamine suppository (Salofalk) once daily is as efficacious as a 500-mg suppository thrice daily in active ulcerative proctitis.

    Science.gov (United States)

    Andus, Tilo; Kocjan, Andreas; Müser, Moritz; Baranovsky, Andrey; Mikhailova, Tatyana L; Zvyagintseva, Tatyana D; Dorofeyev, Andrey E; Lozynskyy, Yurii S; Cascorbi, Ingolf; Stolte, Manfred; Vieth, Michael; Dilger, Karin; Mohrbacher, Ralf; Greinwald, Roland

    2010-11-01

    Mesalamine suppositories are first-line therapy in active ulcerative proctitis; the standard regime still recommends multiple doses per day. The primary objective of this study was to show the noninferiority of once-daily administration of a novel 1 g mesalamine suppository versus thrice-daily administration of the 0.5 g mesalamine suppository. This was a single-blind (investigator-blinded), randomized, multicenter, comparative, Phase III clinical trial. Patients with mild to moderately active ulcerative proctitis inserted either one mesalamine 1 g suppository at bedtime or one mesalamine 0.5 g suppository thrice daily over a 6-week period. The primary endpoint was rate of remission (Disease Activity Index below 4). In all, 354 patients were evaluable for safety and per-protocol analysis. The new regimen demonstrated noninferiority: The percentage of patients with remission was 87.9% for the once-daily 1 g mesalamine suppository and 90.7% for the thrice-daily 0.5 g mesalamine suppository. Each regimen resulted in prompt cessation of clinical symptoms (e.g., median time to ≤3 stools per day (all without blood): 5 days in the 1 g mesalamine once-daily and 7 days in the 0.5 g mesalamine thrice-daily group). Patients preferred applying suppositories once a day. In active ulcerative proctitis the once-daily administration of a 1 g mesalamine suppository is as effective and safe, yet considerably more convenient, than the standard thrice-daily administration of a 0.5 g mesalamine suppository.

  6. Once daily versus conventional dosing of pH-dependent mesalamine long-term to maintain quiescent ulcerative colitis: Preliminary results from a randomized trial

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    Sunanda Kane

    2008-09-01

    Full Text Available Sunanda Kane1, William Holderman2, Peter Jacques2, Todd Miodek31Mayo Clinic College of Medicine, Rochester, MN, USA; 2Digestive Health Specialists, Tacoma, WA, USA; 3University of Chicago, Chicago, IL, USABackground and Aims: Multiple studies have demonstrated the efficacy of aminosalicylates in maintaining remission in ulcerative colitis (UC. A newer formulation of mesalamine can be administered once daily. We aimed to examine the efficacy and tolerability of pH-dependent mesalamine for long-term maintenance, and compare the rates of medication consumption between groups over a prolonged period.Methods: Subjects whose UC had been quiescent for at least 4 months, and who had been receiving mesalamine for maintenance only, were randomized to once daily or conventional dosing for 12 months. Disease activity and medication consumption was assessed every 3 months. The primary endpoint was the percentage of those with quiescent disease at 12 months.Results: We enrolled 20 patients, 12 to once daily and 8 to conventional dosing. Six of the 12 patients (50% in the once daily group compared with 5 of the 8 patients (62.5% in the conventional group experienced a flare (p = 0.31. Only 5 of the 12 (42% patients in the once daily group were adherent compared with 3 of 8 patients (37.5% in the conventional dosing group (p = NS. Median amount consumed in the once daily group was 63% (range 0%–100% and in the conventional group 55% (range 0%–100%, (p > 0.5. None of the adherent subjects in the once daily group experienced a flare, while 6 out of 7 (86% who were non-adherent experienced a flare (p < 0.01. In the conventional dosing group, 1 in 3 adherent patients (33% experienced a fl are compared with 4 out of 5 (80% in the non-adherent group (p < 0.01.Conclusion: Adherence, rather than medication regimen, appeared to be important in disease outcome at 12 months.Keywords: ulcerative colitis, mesalamine, aminosalicylates, remission

  7. Once daily oral mesalamine compared to conventional dosing for induction and maintenance of remission in ulcerative colitis: a systematic review and meta-analysis.

    Science.gov (United States)

    Feagan, Brian G; MacDonald, John K

    2012-09-01

    We systematically reviewed and compared the efficacy and safety of once daily (OD) mesalamine to conventional dosing for induction and maintenance of remission in ulcerative colitis (UC). A literature search to January 2012 identified all applicable randomized trials. Study quality was evaluated using the Cochrane risk of bias tool. The GRADE criteria were used to assess the overall quality of the evidence. Studies were subgrouped by formulation for meta-analysis. Eleven studies that evaluated 4070 patients were identified. The risk of bias was low for most factors, although five studies were single-blind and one was open-label. No difference was observed between the dosing strategies in the proportion of patients with clinical remission (relative risk [RR] 0.95; 95% confidence interval [CI] 0.82-1.10), clinical improvement (RR 0.87 95% CI 0.68-1.10), or relapse at 6 (RR 1.10; 95% CI 0.83-1.46) or 12 months (RR 0.92; 95% CI 0.83-1.03). Subgroup analyses showed no important differences in efficacy. No significant difference was demonstrated in rates of medication adherence or adverse events between OD and conventional dosing. OD mesalamine appears to be as effective and safe as conventional dosing for both the treatment of mild to moderately active UC and for maintenance of remission in quiescent UC. The failure to demonstrate a superior rate of adherence to OD dosing may be due to the high rate of adherence observed in the clinical trials environment. Future research should assess the value of OD dosing in community settings.

  8. Update on the management of ulcerative colitis: treatment and maintenance approaches focused on MMX® mesalamine

    Directory of Open Access Journals (Sweden)

    Nanda K

    2012-07-01

    Full Text Available Kavinderjit Nanda, Alan C MossCenter for Inflammatory Bowel Disease, BIDMC/Harvard Medical School, Boston, MA, USAAbstract: Ulcerative colitis (UC is a chronic inflammatory disease of the colon that typically manifests as diarrhea, abdominal pain, and bloody stool. Complications, such as colorectal cancer and extraintestinal manifestations, may also develop. The goals of management are to induce and maintain clinical remission and to screen for complications of this disease. Mesalamine is a 5-aminosalicylic acid compound that is the first-line therapy to induce and maintain clinical remission in patients with mild-to-moderate UC. For patients who are refractory to mesalamine or have more severe disease, steroids, azathioprine/mercaptopurine, cyclosporine, or infliximab may be used, induce and/or maintain remission. The various formulations of mesalamine available are primarily differentiated by the methods of delivery of the active compound of the drug to the colon. Mesalamine with Multi-Matrix System® (MMX technology (Cosmo SpA, Milan, Italy is an oral (1.2 g, once-daily tablet formulation of mesalamine used for the treatment of UC (Lialda® or Mezavant®, Shire Pharmaceuticals Inc, Wayne, PA. In clinical studies, MMX mesalamine (taken as a once-daily dose of 2.4 or 4.8 g effectively induced and maintained clinical remission in patients with active mild-to-moderate UC. The overall safety profile of MMX mesalamine is similar to other oral mesalamine formulations. The use of such once-daily formulations has led to intense interest in whether simplified pill regimens can improve patient adherence to mesalamine therapy.Keywords: mesalamine, 5-ASA, ulcerative colitis, inflammatory bowel disease

  9. Release of 5-aminosalicylate from an MMX mesalamine tablet during transit through a simulated gastrointestinal tract system

    NARCIS (Netherlands)

    Tenjarla, S.; Romasanta, V.; Zeijdner, E.; Villa, R.; Moro, L.

    2007-01-01

    5-Aminosalicylate (5-ASA; mesalamine) is the current first-line treatment for mild to moderate ulcerative colitis, a chronic inflammatory condition that most commonly affects the distal part of the colon. MMX™ mesalamine (Lialda™ [US]; Mezavant™ XL [UK and Ireland]; Mezavant™ [elsewhere]; Shire Phar

  10. Effect of MMX® mesalamine coadministration on the pharmacokinetics of amoxicillin, ciprofloxacin XR, metronidazole, and sulfamethoxazole: results from four randomized clinical trials

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    Pierce D

    2014-05-01

    Full Text Available David Pierce,1 Mary Corcoran,2 Patrick Martin,2 Karen Barrett,1 Susi Inglis,1 Peter Preston,2 Thomas N Thompson,3 Sandra K Willsie3 1Shire, Basingstoke, UK; 2Shire, Wayne, PA, USA; 3PRA International, Lenexa, KS, USA Background: MMX® mesalamine is a once daily oral 5-aminosalicylic acid formulation, effective in induction and maintenance of ulcerative colitis remission. Patients on long-term mesalamine maintenance may occasionally require concomitant antibiotic treatment for unrelated infections. Aim: To evaluate the potential for pharmacokinetic interactions between MMX mesalamine and amoxicillin, ciprofloxacin extended release (XR, metronidazole, or sulfamethoxazole in four open-label, randomized, placebo-controlled, two-period crossover studies. Methods: In all four studies, healthy adults received placebo once daily or MMX mesalamine 4.8 g once daily on days 1–4 in one of two treatment sequences. In studies 1 and 2, subjects also received a single dose of amoxicillin 500 mg (N=62 or ciprofloxacin XR 500 mg (N=30 on day 4. In studies 3 and 4, subjects received metronidazole 750 mg twice daily on days 1–3 and once on day 4 (N=30; or sulfamethoxazole 800 mg/trimethoprim 160 mg twice daily on days 1–3 and once on day 4 (N=44. Results: MMX mesalamine had no significant effects on systemic exposure to amoxicillin, ciprofloxacin, or metronidazole; the 90% confidence intervals (CIs around the geometric mean ratios (antibiotic + MMX mesalamine: antibiotic + placebo for maximum plasma concentration (Cmax and area under the plasma concentration–time curve (AUC fell within the predefined equivalence range (0.80–1.25. Sulfamethoxazole exposure increased by a statistically significant amount when coadministered with MMX mesalamine; however, increased exposure (by 12% in Cmax at steady state; by 15% in AUC at steady state was not considered clinically significant, as the 90% CIs for each point estimate fell entirely within the predefined

  11. Update on the management of ulcerative colitis: treatment and maintenance approaches focused on MMX® mesalamine. [Corrigendum

    Directory of Open Access Journals (Sweden)

    Nanda K

    2013-01-01

    Full Text Available Nanda K, Moss AC.Clinical Pharmacology: Advances and Applications. 2012, 4:41–50.The authors apologize for errors on Tables 1, 2, and 3.Table1Citation 40, Hussain et al, should have been citation 44, Shire US Inc.Table 2Lichtenstein et al data, the confidence interval (CI of the odds ratio for achieving remission with MMX mesalamine 1.2 g twice daily (1.44–8.41 should be listed as a 97.5% CI rather than a 95% CI.Table 3Prantera et al, the MMX mesalamine 2.4 g once daily cohort should have an N value of 156, not 162, and the 12-month relapse rate should be 25.0%, not 15.0%.Pramtera et al, the Asacol 2.4 g once daily cohort should be labeled "Asacol 2.4 g/day twice daily", and should have an N value of 167, not 156.Kane et al, the N value should be 194, not 167.Read the original article

  12. Mesalamine Rectal

    Science.gov (United States)

    Rectal mesalamine comes as a suppository and an enema to use in the rectum. The suppository and the enema are usually used once a day at bedtime. ... rectal mesalamine without talking to your doctor.Mesalamine suppositories and enemas may stain clothing and other fabrics, ...

  13. A dynamic model of once-daily 5-aminosalicylic acid predicts clinical efficacy

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    Deepak; Parakkal; Eli; D; Ehrenpreis; Matthew; P; Thorpe; Karson; S; Putt; Bruce; Hannon

    2010-01-01

    New once daily mesalamine formulations may improve adherence to medication usage.Response to Asacol and other forms of 5-aminosalicyclic acid(5-ASA)is better correlated with tissue concentrations and best predicted by concentrations of the drug within the lumen of the colon.Our group used computer simulation to predict colonic 5-ASA levels after Asacol administration.In our study,the model simulated Asacol distribution in the healthy colon,and during quiescent and active ulcerative colitis.An Asacol dosage ...

  14. Encapsulated mesalamine granules (Apriso) for ulcerative colitis.

    Science.gov (United States)

    2009-05-18

    Apriso (Salix) is a new formulation of mesalamine (5-aminosalicylic acid; 5-ASA) approved by the FDA for maintenance of remission in mild to moderate ulcerative colitis (UC). Mesalamine is a locally acting antiinflammatory agent that is widely used both to maintain and induce remission in inflammatory bowel disease. Various mesalamine formulations have been developed to target drug delivery to areas of the small intestine and colon. Most of these agents require frequent dosing and have a high pill burden. The newest products--Lialda, introduced in 2007, and now Apriso--can be dosed once daily.

  15. Long-term efficacy and safety of once-daily mesalazine granules for the treatment of active ulcerative colitis

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    Böhm SK

    2014-09-01

    Full Text Available Stephan Karl Böhm,1 Wolfgang Kruis2 1Kantonsspital Baselland, Medizinische Universitätsklinik, Bruderholz, Switzerland; 2Evangelisches Krankenhaus Kalk, University of Cologne, Cologne, Germany Abstract: In 1977, 5-aminosalicylic acid (5-ASA was discovered as a therapeutically active moiety of sulfasalazine (SASP and was launched for topical and oral therapy of ulcerative colitis (UC in 1984. As a first-step, delivery systems had to be developed to protect 5-ASA against absorption in the upper gastrointestinal tract, resulting in different and competing strategies (azo compounds, controlled release, and pH-dependent release. In a second step, at the beginning of the new century, coinciding with the expiration of patent protection for the first 5-ASA formulations, two component composite release mechanisms (pH-dependent and controlled release were developed. Furthermore, the drug was formulated as granules instead of tablets, allowing higher unit strengths compared with tablets. Neither Salofalk Granu-Stix®, nor MMX 5-ASA, nor Pentasa® granules have initially been developed for once-daily (OD dosing. A review of the achievements of 20 years of 5-ASA development has demonstrated that 5-ASA has equal efficacy compared with SASP at best, that there are no measurable differences in efficacy between various 5-ASA preparations, and that in a group of patients tolerating SASP, adverse event profiles of SASP and 5-ASA did not differ significantly, with SASP being the far cheaper substance. Therefore, drug adherence came into focus as a new goal for improving UC therapy. Although adherence is a complex and multifactorial construct, a simple dosing schedule may contribute to higher drug adherence and better efficacy of treatment. Simultaneously, the US 5-ASA market, estimated to be worth US$1.4 billion, is expected to grow continuously. Naturally, this very competitive market is not only driven by scientific progress but also by commercial interests

  16. Pharmacokinetics and pharmacodynamics of boosted once-daily darunavir.

    Science.gov (United States)

    Kakuda, Thomas N; Brochot, Anne; Tomaka, Frank L; Vangeneugden, Tony; Van De Casteele, Tom; Hoetelmans, Richard M W

    2014-10-01

    The ability to dose antiretroviral agents once daily simplifies the often complex therapeutic regimens required for the successful treatment of HIV infection. Thus, once-daily dosing can lead to improved patient adherence to medication and, consequently, sustained virological suppression and reduction in the risk of emergence of drug resistance. Several trials have evaluated once-daily darunavir/ritonavir in combination with other antiretrovirals (ARTEMIS and ODIN trials) or as monotherapy (MONET, MONOI and PROTEA trials) in HIV-1-infected adults. Data from ARTEMIS and ODIN demonstrate non-inferiority of once-daily darunavir/ritonavir against a comparator and, together with pharmacokinetic data, have established the suitability of once-daily darunavir/ritonavir for treatment-naive and treatment-experienced patients with no darunavir resistance-associated mutations. The findings of ARTEMIS and ODIN have led to recent updates to treatment guidelines, whereby once-daily darunavir/ritonavir, given with other antiretrovirals, is now a preferred treatment option for antiretroviral-naive adult patients and a simplified treatment option for antiretroviral-experienced adults who have no darunavir resistance-associated mutations. Once-daily dosing with darunavir/ritonavir is an option for treatment-naive and for treatment-experienced paediatric patients with no darunavir resistance-associated mutations based on the findings of the DIONE trial and ARIEL substudy. This article reviews the pharmacokinetics, efficacy, safety and tolerability of once-daily boosted darunavir. The feasibility of darunavir/ritonavir monotherapy as a treatment approach for some patients is also discussed. Finally, data on a fixed-dose combination of 800/150 mg of darunavir/cobicistat once daily are presented, showing comparable darunavir bioavailability to that obtained with 800/100 mg of darunavir/ritonavir once daily. © The Author 2014. Published by Oxford University Press on behalf of the British

  17. Pharmacokinetic profile of once-daily cyclobenzaprine extended-release.

    Science.gov (United States)

    Darwish, Mona; Hellriegel, Edward T

    2010-11-01

    Cyclobenzaprine immediate-release (CIR) is a widely prescribed skeletal muscle relaxant with an established efficacy and safety profile in patients with muscle spasm associated with acute, painful conditions, although it is commonly associated with sedation. CIR is typically prescribed at a dosage of 10 mg three-times-daily. This review focuses on the pharmacokinetic profile of a new formulation, cyclobenzaprine extended-release (CER), which delivers a sustained plasma cyclobenzaprine concentration over 24 h, allowing once-daily dosing. Results from CER pharmacokinetic studies conducted through August 2010 are summarized. This review provides information on the first four studies assessing the single-dose and steady-state pharmacokinetic profile of CER. Once-daily CER 30 mg and three-times-daily CIR 10 mg produced comparable systemic exposures to cyclobenzaprine, but pharmacokinetic profiles were qualitatively different. CER was characterized by a single daily peak in cyclobenzaprine concentration versus three peaks/day for CIR. With once-daily dosing of CER, cyclobenzaprine concentration is sustained over 24 h. CER 30 mg provides approximately twice the exposure as CER 15 mg. Systemic exposure to CER is increased in the presence of food and in elderly subjects. Steady-state is achieved by day 7 of dosing.

  18. Once-Daily Radiation Therapy for Inflammatory Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Brown, Lindsay [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States); Harmsen, William [Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota (United States); Blanchard, Miran [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States); Goetz, Matthew [Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota (United States); Jakub, James [Department of Surgery, Mayo Clinic, Rochester, Minnesota (United States); Mutter, Robert; Petersen, Ivy; Rooney, Jessica [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States); Stauder, Michael [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Yan, Elizabeth [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States); Laack, Nadia, E-mail: laack.nadia@mayo.edu [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States)

    2014-08-01

    Purpose: Inflammatory breast cancer (IBC) is a rare and aggressive breast cancer variant treated with multimodality therapy. A variety of approaches intended to escalate the intensity and efficacy of radiation therapy have been reported, including twice-daily radiation therapy, dose escalation, and aggressive use of bolus. Herein, we examine our outcomes for patients treated with once-daily radiation therapy with aggressive bolus utilization, focusing on treatment technique. Methods and Materials: A retrospective review of patients with nonmetastatic IBC treated from January 1, 2000, through December 31, 2010, was performed. Locoregional control (LRC), disease-free survival (DFS), overall survival (OS) and predictors thereof were assessed. Results: Fifty-two women with IBC were identified, 49 (94%) of whom were treated with neoadjuvant chemotherapy. All underwent mastectomy followed by adjuvant radiation therapy. Radiation was delivered in once-daily fractions of 1.8 to 2.25 Gy (median, 2 Gy). Patients were typically treated with daily 1-cm bolus throughout treatment, and 33 (63%) received a subsequent boost to the mastectomy scar. Five-year Kaplan Meier survival estimates for LRC, DFS, and OS were 81%, 56%, and 64%, respectively. Locoregional recurrence was associated with poorer OS (P<.001; hazard ratio [HR], 4.1). Extracapsular extension was associated with worse LRC (P=.02), DFS (P=.007), and OS (P=.002). Age greater than 50 years was associated with better DFS (P=.03). Pathologic complete response was associated with a trend toward improved LRC (P=.06). Conclusions: Once-daily radiation therapy with aggressive use of bolus for IBC results in outcomes consistent with previous reports using various intensified radiation therapy regimens. LRC remains a challenge despite modern systemic therapy. Extracapsular extension, age ≤50 years, and lack of complete response to chemotherapy appear to be associated with worse outcomes. Novel strategies are needed in IBC

  19. Mesalamine-Induced Myocarditis

    OpenAIRE

    Pierre-Louis Michel; Richard Dorent; Nadjib Hammoudi; Florence Pontnau; Antoine Khalil; Clement Bailly; Olivier Merceron

    2010-01-01

    Nowadays mesalamine is a common treatment for Crohn's disease and hypersensitive reactions to this product have been reported. Yet there is limited information concerning mesalamine-induced myocarditis and its mechanism is not known. We described a case of mesalamine-induced myocarditis in Crohn's disease of the colon.

  20. Mesalamine-Induced Myocarditis

    Directory of Open Access Journals (Sweden)

    Olivier Merceron

    2010-01-01

    Full Text Available Nowadays mesalamine is a common treatment for Crohn's disease and hypersensitive reactions to this product have been reported. Yet there is limited information concerning mesalamine-induced myocarditis and its mechanism is not known. We described a case of mesalamine-induced myocarditis in Crohn's disease of the colon.

  1. Once daily dose gentamicin in neonates - is our dosing correct?

    Science.gov (United States)

    Serane, Tiroumourougane V; Zengeya, Stanley; Penford, Gemma; Cooke, Jane; Khanna, Gitika; McGregor-Colman, Elle

    2009-07-01

    The aim of this paper is to study the safety and efficacy (measured by therapeutic level) of once daily gentamicin in neonates >or=32 weeks of gestation and or=32 weeks of gestation and 2 mg/L. Only 39 (60%) had peak and trough levels within the therapeutic range. All babies who had audiometric evaluation (62 out of 65) had normal hearing. Out of the 65 babies, 60 had paired serum creatinine levels estimated and none had evidence of renal dysfunction. Among term neonates, only 2 out of 50 had the trough serum concentration of >2 mg/L. In 38 (76%) of the 50 neonates, the trough serum gentamicin concentration was <2.0 mg/L and the peak level was <10 mg/L. Forty-eight babies had audiometric evaluation which was normal. A dose of 4 mg/kg/day produces serum gentamicin levels outside the therapeutic range in two-fifths of neonates between 32 and 36 +/- 6 weeks. A single dose of 4 mg/kg/day of gentamicin is appropriate for term babies and probably excessive for 32-36 weeks' neonates.

  2. Once-daily antiretroviral therapy in a cohort of HIV-infected children and adolescents.

    Science.gov (United States)

    Jiménez-Montero, Beatriz; Beceiro, José; de José-Gómez, M Isabel; González-Tomé, M Isabel; Gurbindo-Gutierrez, Dolores; Martínez-Pérez, Jorge; Mellado-Peña, M José; Navarro-Gómez, M Luisa; Roa-Francia, Miguel A; Rojo-Conejo, Pablo; Saavedra-Lozano, Jesús; Jiménez de Ory, Santiago; Ramos-Amador, José T

    2014-10-01

    We evaluated the evolution over time of once-daily antiretroviral therapy in HIV-infected children and its relationship with adherence. An increase on the prevalence of once-daily antiretroviral therapy was observed over time (from 0.9% in 2002 to 44.2% in 2011). There was no difference in adherence regarding once-daily or BID regimens in 2011. Adherence was related to age and pill burden.

  3. Once-daily medications for the pharmacological management of ADHD in adults

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    Oleg v Tcheremissine

    2009-05-01

    Full Text Available Oleg v Tcheremissine1, Lori M Lieving21Department of Psychiatry, Behavioral Health Center – Carolinas Medical Center, Charlotte, NC, USA; 2Carolinas College of Health Sciences, Charlotte, NC, USAAbstract: Attention-deficit/hyperactivity disorder (ADHD is the most commonly diagnosed psychiatric disorder in children and adolescents. Symptoms of ADHD often persist beyond childhood and present significant challenges to adults. Pharmacotherapy is a first-line treatment option for ADHD across all age groups. The current review’s goals are (a to critically examine the current state of knowledge regarding once-daily formulations of pharmacotherapies for treatment of adults with ADHD and (b to provide clinicians with evidence-based information regarding the safety, efficacy and tolerability of once-daily medications for adult ADHD. The reviewed body of evidence strongly supports the use of pharmacotherapy as a first-line therapeutic option for the treatment of adults with ADHD. The once-daily pharmacological agents are effective therapeutic options for the treatment of adults with ADHD. In the US, based on the available evidence, once-daily medications are currently underutilized in adults with ADHD compared to pediatric population.Keywords: adults, attention deficit/hyperactivity disorder, once-daily pharmacotherapies

  4. Twice-Daily versus Once-Daily Pramipexole Extended Release Dosage Regimens in Parkinson's Disease.

    Science.gov (United States)

    Yun, Ji Young; Kim, Young Eun; Yang, Hui-Jun; Kim, Han-Joon; Jeon, Beomseok

    2017-01-01

    This open-label study aimed to compare once-daily and twice-daily pramipexole extended release (PER) treatment in Parkinson's disease (PD). PD patients on dopamine agonist therapy, but with unsatisfactory control, were enrolled. Existing agonist doses were switched into equivalent PER doses. Subjects were consecutively enrolled into either once-daily-first or twice-daily-first groups and received the prescribed amount in one or two, respectively, daily doses for 8 weeks. For the second period, subjects switched regimens in a crossover manner. The forty-four patients completed a questionnaire requesting preference during their last visit. We measured the UPDRS-III, Hoehn and Yahr stages (H&Y) in medication-on state, Parkinson's disease sleep scale (PDSS), and Epworth Sleepiness Scale. Eighteen patients preferred a twice-daily regimen, 12 preferred a once-daily regimen, and 14 had no preference. After the trial, 14 subjects wanted to be on a once-daily regimen, 25 chose a twice-daily regimen, and 5 wanted to maintain the prestudy regimen. Main reasons for choosing the twice-daily regimen were decreased off-duration, more tolerable off-symptoms, and psychological stability. The mean UPDRS-III, H&Y, and PDSS were not different. Daytime sleepiness was significantly high in the once-daily regimen, whereas nocturnal hallucinations were more common in the twice-daily. Multiple dosing should be considered if once-daily dosing is unsatisfactory. This study is registered as NCT01515774 at ClinicalTrials.gov.

  5. Efficacy and safety of once daily low molecular weight heparin (tinzaparin sodium) in high risk pregnancy.

    LENUS (Irish Health Repository)

    Ní Ainle, Fionnuala

    2008-10-01

    Low molecular weight heparin (LMWH) is widely regarded as the anticoagulant treatment of choice for the prevention and treatment of venous thromboembolism during pregnancy. However, previous studies have demonstrated that the pharmacokinetic profiles of LMWH vary significantly with increasing gestation. Consequently, it remains unclear whether LMWH regimens recommended for use in nonpregnant individuals can be safely extrapolated to pregnant women. The aims of this study were to assess the safety and the efficacy of tinzaparin sodium (Innohep) administered only once daily during pregnancy. A systematic retrospective review identified a cohort of 37 high-risk pregnancies which had been managed using tinzaparin 175 IU\\/kg once daily. In 26 cases, the index pregnancy had been complicated by development of an acute venous thromboembolism (17 deep vein thrombosis and nine pulmonary embolism). For each individual, case notes were examined and data extracted using a predetermined questionnaire. No episodes of recurrent venous thromboembolism were identified amongst this cohort of pregnancies managed using once daily LMWH administration. However, two unusual thrombotic complications were observed, including a parietal infarct in one patient, and a postpartum cerebral venous thrombosis in another. Once daily tinzaparin was well tolerated, with no cases of heparin-induced thrombocytopaenia, symptomatic osteoporosis, or foetal malformations. Tinzaparin dose modification based upon peak anti-Xa levels occurred in 45% of the cases examined. The present study is the largest study to have examined the clinical efficacy of once daily LMWH for use in pregnant women at high risk of venous thromboembolism. Our data support the safety and efficacy of antenatal tinzaparin at a dose of 175 IU\\/kg. In order to determine whether this once daily regimen provides equivalent (or indeed greater) thromboprophylaxis to twice daily LMWH regimens during pregnancy will require highly powered

  6. Twice-Daily versus Once-Daily Pramipexole Extended Release Dosage Regimens in Parkinson's Disease

    Science.gov (United States)

    Kim, Young Eun; Yang, Hui-Jun; Kim, Han-Joon

    2017-01-01

    This open-label study aimed to compare once-daily and twice-daily pramipexole extended release (PER) treatment in Parkinson's disease (PD). PD patients on dopamine agonist therapy, but with unsatisfactory control, were enrolled. Existing agonist doses were switched into equivalent PER doses. Subjects were consecutively enrolled into either once-daily-first or twice-daily-first groups and received the prescribed amount in one or two, respectively, daily doses for 8 weeks. For the second period, subjects switched regimens in a crossover manner. The forty-four patients completed a questionnaire requesting preference during their last visit. We measured the UPDRS-III, Hoehn and Yahr stages (H&Y) in medication-on state, Parkinson's disease sleep scale (PDSS), and Epworth Sleepiness Scale. Eighteen patients preferred a twice-daily regimen, 12 preferred a once-daily regimen, and 14 had no preference. After the trial, 14 subjects wanted to be on a once-daily regimen, 25 chose a twice-daily regimen, and 5 wanted to maintain the prestudy regimen. Main reasons for choosing the twice-daily regimen were decreased off-duration, more tolerable off-symptoms, and psychological stability. The mean UPDRS-III, H&Y, and PDSS were not different. Daytime sleepiness was significantly high in the once-daily regimen, whereas nocturnal hallucinations were more common in the twice-daily. Multiple dosing should be considered if once-daily dosing is unsatisfactory. This study is registered as NCT01515774 at ClinicalTrials.gov. PMID:28265478

  7. The pharmacokinetics of abacavir 600 mg once daily in HIV-1-positive pregnant women

    NARCIS (Netherlands)

    Schalkwijk, S.J.; Colbers, A.; Konopnicki, D.; Weizsacker, K.; Molto, J.; Tenorio, C.H.; Hawkins, D.; Taylor, G.; Wood, C.; Ende, M. van der; Burger, D.M.

    2016-01-01

    OBJECTIVE: To describe the pharmacokinetics of abacavir 600 mg once daily (q.d.) in HIV-1-positive women during pregnancy and postpartum. DESIGN: A nonrandomized, open-label, multicentre, phase-IV study. METHODS: HIV-positive pregnant women receiving abacavir 600 mg q.d. as part of clinical care wer

  8. The pharmacokinetics of abacavir 600 mg once daily in HIV-1-positive pregnant women

    NARCIS (Netherlands)

    Schalkwijk, S.J.; Colbers, A.; Konopnicki, D.; Weizsacker, K.; Molto, J.; Tenorio, C.H.; Hawkins, D.; Taylor, G.; Wood, C.; Ende, M. van der; Burger, D.M.

    2016-01-01

    OBJECTIVE: To describe the pharmacokinetics of abacavir 600 mg once daily (q.d.) in HIV-1-positive women during pregnancy and postpartum. DESIGN: A nonrandomized, open-label, multicentre, phase-IV study. METHODS: HIV-positive pregnant women receiving abacavir 600 mg q.d. as part of clinical care wer

  9. Benefits of once-daily therapies in the treatment of hypertension

    Science.gov (United States)

    Flack, John M; Nasser, Samar A

    2011-01-01

    In patients with hypertension, 24-hour blood pressure control is the major therapeutic goal. The number of daily doses is one characteristic of an antihypertensive agent that may affect the adequacy of 24-hour control. One measure of therapeutic coverage is the 24-hour trough-to-peak ratio, which determines the suitability of an agent for once-daily administration. The closer an agent is to a 100% trough-to-peak ratio, the more uniform the 24-hour coverage and therefore blood pressure control. High trough-to-peak ratio, long-acting antihypertensive medications lower blood pressure more gradually, which reduces the likelihood of adverse events attributable to abrupt drug action that occurs with shorter-acting agents. In hypertension, the natural diurnal variation of blood pressure may be altered, including elevated nighttime pressures. An optimal once-daily hypertension therapy would not only lower blood pressure but also normalize any blunted circadian variations in blood pressure. The benefits of once-daily agents with sustained therapeutic coverage may also be explained, in part, by increased patient adherence to simpler regimens as well as lower loss of blood pressure control during virtually inevitable intermittent noncompliance. Studies have demonstrated that once-daily antihypertensive agents have the highest adherence compared with twice-daily or multiple daily doses, including greater adherence to the prescribed timing of doses. PMID:22241952

  10. Effects of Once-Daily Oral and Transdermal Methylphenidate on Sleep Behavior of Children with ADHD

    Science.gov (United States)

    Faraone, Stephen V.; Glatt, Stephen J.; Bukstein, Oscar G.; Lopez, Frank A.; Arnold, L. Eugene; Findling, Robert L.

    2009-01-01

    Objective: Methylphenidate is a leading first-line treatment for ADHD (AD/HD). This stimulant has long been suspected to adversely affect sleeping patterns of treated individuals, especially children. There are few studies on the effects of recently developed longer-acting methylphenidate treatments, such as once-daily oral or transdermal…

  11. Once-daily dolutegravir is superior to once-daily darunavir/ritonavir in treatment-naïve HIV-1-positive individuals: 96 week results from FLAMINGO

    Directory of Open Access Journals (Sweden)

    Jean-Michel Molina

    2014-11-01

    Full Text Available Introduction: Dolutegravir (DTG 50 mg once daily was superior to darunavir/ritonavir (DRV/r 800 mg/100 mg once daily through Week 48, with 90% vs. 83% of participants achieving HIV RNA 50 c/mL (p=0.025 [1]. We present data through Week 96. Material and Methods: FLAMINGO is a multicentre, randomized, open-label, Phase IIIb non-inferiority study, in which HIV-1-positive ART-naïve adults with HIV-1 RNA≥1000 c/mL and no evidence of viral resistance were randomized 1:1 to receive DTG or DRV/r, with investigator-selected backbone NRTIs (TDF/FTC or ABC/3TC. Participants were stratified by screening HIV-1 RNA (≤100K c/mL and NRTI backbone. Results: A total of 484 adults were randomized and treated; 25% had baseline HIV RNA 100K c/mL. At Week 96, the proportion of participants with HIV RNA 50 c/mL was 80% in the DTG arm vs. 68% in the DRV/r arm (adjusted difference 12.4%; 95% CI 4.7, 20.2%; p=0.002. Secondary analyses supported primary results: per-protocol [(DTG 83% vs. DRV/r 70%, 95% CI 12.9 (5.3, 20.6] and treatment-related discontinuation = failure [(98% vs. 95%, 95% CI 3.2 (−0.3, 6.7]. Overall virologic non-response (DTG 8%; DRV/r 12% and non-response due to other reasons (DTG 12%; DRV/r 21% occurred less frequently on DTG. As at Week 48, the difference between arms was most pronounced in participants with high baseline viral load (82% vs. 52% response through Week 96 and in the TDF/FTC stratum (79% vs. 64%; consistent responses were seen in the ABC/3TC stratum (82% vs. 75%. Six participants (DTG 2, none post-Week 48; DRV/r 4, two post-Week 48 experienced protocol-defined virologic failure (PDVF; confirmed viral load 200 c/mL on or after Week 24; none had treatment-emergent resistance to study drugs. Most frequent drug-related adverse events (AEs were diarrhoea, nausea and headache, with diarrhoea significantly more common on DRV/r (24% than DTG (10%. Significantly more participants had Grade 2 fasting LDL toxicities on DRV/r (22% vs. DTG (7

  12. Long-term efficacy and safety of once-daily mesalazine granules for the treatment of active ulcerative colitis.

    Science.gov (United States)

    Böhm, Stephan Karl; Kruis, Wolfgang

    2014-01-01

    In 1977, 5-aminosalicylic acid (5-ASA) was discovered as a therapeutically active moiety of sulfasalazine (SASP) and was launched for topical and oral therapy of ulcerative colitis (UC) in 1984. As a first-step, delivery systems had to be developed to protect 5-ASA against absorption in the upper gastrointestinal tract, resulting in different and competing strategies (azo compounds, controlled release, and pH-dependent release). In a second step, at the beginning of the new century, coinciding with the expiration of patent protection for the first 5-ASA formulations, two component composite release mechanisms (pH-dependent and controlled release) were developed. Furthermore, the drug was formulated as granules instead of tablets, allowing higher unit strengths compared with tablets. Neither Salofalk Granu-Stix(®), nor MMX 5-ASA, nor Pentasa(®) granules have initially been developed for once-daily (OD) dosing. A review of the achievements of 20 years of 5-ASA development has demonstrated that 5-ASA has equal efficacy compared with SASP at best, that there are no measurable differences in efficacy between various 5-ASA preparations, and that in a group of patients tolerating SASP, adverse event profiles of SASP and 5-ASA did not differ significantly, with SASP being the far cheaper substance. Therefore, drug adherence came into focus as a new goal for improving UC therapy. Although adherence is a complex and multifactorial construct, a simple dosing schedule may contribute to higher drug adherence and better efficacy of treatment. Simultaneously, the US 5-ASA market, estimated to be worth US$1.4 billion, is expected to grow continuously. Naturally, this very competitive market is not only driven by scientific progress but also by commercial interests. Thus, patents for minor changes to the formulation may serve as protection against drug companies trying to launch generic versions. Randomized controlled trials performed on OD dosing in induction of remission have

  13. The antianginal efficacy and tolerability of controlled-release metoprolol once daily

    DEFF Research Database (Denmark)

    Egstrup, K; Gundersen, T; Härkönen, R;

    1988-01-01

    In a randomized, double-blind, cross-over study treatment with a new controlled-release (CR) preparation of metoprolol, given once daily, was compared with treatment with conventional metoprolol tablets, given twice daily, in 115 patients with stable effort angina pectoris. The patients were...... questionnaire. When all patients were analysed together there were no differences in antianginal efficacy between the two treatment regimens. However, when the group taking 200 mg daily was analysed separately better exercise tolerance was found during metoprolol CR therapy, as measured by onset of chest pain...... and ST-segment change, compared with conventional metoprolol therapy. The two formulations were well tolerated. When given once daily in a total daily dose of 100 mg, the CR preparation induced less adverse effects than the conventional tablets, 50 mg twice daily. It was concluded that the new metoprolol...

  14. Profile of glycopyrronium for once-daily treatment of moderate-to-severe COPD

    Directory of Open Access Journals (Sweden)

    Buhl R

    2012-10-01

    Full Text Available Roland Buhl,1 Donald Banerji21Pulmonary Department, Mainz University Hospital, Mainz, Germany; 2Novartis Pharmaceuticals Corporation, East Hanover, NJ, USAAbstract: Bronchodilators are central in the symptomatic management of chronic obstructive pulmonary disease (COPD. Long-acting muscarinic antagonists (LAMAs and long-acting β2-agonists (LABAs are the main classes of long-acting bronchodilators. To date, tiotropium is the only once-daily LAMA available for the treatment of COPD. Glycopyrronium is a novel LAMA, currently in development for COPD. Phase II studies have shown that glycopyrronium 50 µg once daily provides clinically significant 24-hour bronchodilation with a rapid onset of action, which is faster than that of tiotropium, and a favorable safety and tolerability profile. The Phase III GLycopyrronium bromide in COPD airWays (GLOW program has now confirmed the long-term efficacy and tolerability of glycopyrronium 50 µg once daily. The three studies included in this program have further shown that the effect of glycopyrronium versus placebo is similar to that of tiotropium in reducing dyspnea and the risk of exacerbations, as well as improving lung function, exercise tolerance, and health status in patients with COPD. The safety profile of glycopyrronium is also similar to that of tiotropium in terms of overall incidence of adverse events and muscarinic side effects. Glycopyrronium could be an alternative choice to tiotropium, and like tiotropium, has the potential to be used as a monotherapy or combination therapy. Phase II studies have shown that a fixed-dose combination of glycopyrronium and the 24-hour LABA indacaterol, produces rapid and sustained bronchodilation compared with indacaterol monotherapy in patients with COPD. Phase III studies are currently ongoing to assess the long-term efficacy and safety of this combination.Keywords: NVA237, glycopyrronium, chronic obstructive pulmonary disease, once daily, muscarinic

  15. Liraglutide: a once-daily GLP-1 analogue for the treatment of type 2 diabetes mellitus

    DEFF Research Database (Denmark)

    Vilsbøll, Tina

    2007-01-01

    properties that are suitable for once-daily dosing. Liraglutide has demonstrated lasting improvement of HbA(1c )levels, weight reduction and improved beta-cell function in patients with Type 2 diabetes mellitus. Liraglutide is well tolerated; the adverse events that are most frequently reported being...... transient nausea and diarrhoea. This article reviews the mechanisms of action and efficacy of liraglutide for the treatment of Type 2 diabetes mellitus. This agent is presently in Phase III clinical development....

  16. Update on the clinical utility of once-daily tacrolimus in the management of transplantation

    Directory of Open Access Journals (Sweden)

    Revollo J

    2015-05-01

    Full Text Available Jane Revollo Department of Pharmacy, Jackson Memorial Hospital, University of Miami Leonard M Miller School of Medicine Miami, FL, USAThe review by Posadas Salas and Srinivas of the clinical utility of once-daily tacrolimus formulations in the management of transplant patients1 was timely and relevant. It is worth noting, however, the data were presented in a way that overlooked several key differences between two distinct once-daily tacrolimus formulations. These formulations differ in bioavailability, Cmax, Tmax, dose required to achieve target trough levels, and time to reach target trough. The specific formulation and dosing information of one product was detailed in this review (described as modified release 4 [MR-4]; Astagraf®, Astellas Pharma Inc., Tokyo, Japan, but no formulation or dosing details were provided for a very different once-daily tacrolimus formulation (LCP-Tacro™; Veloxis Pharmaceuticals A/S, Hørsholm, Denmark for which a thorough review was recently published.2 The latter product is currently approved in Europe and under review by the US Food and Drug Administration in the US. In presenting data in this review, the authors did not identify which product was investigated in each of the studies discussed. This could easily lead to misinterpretation of results or erroneous conclusions, ie, that both once-daily formulations are the same. In fact, a careful parsing of the data clearly demonstrates that they are not equivalent. Misunderstanding of this point could have a potentially serious impact on appropriate dosing, safety, and patient management in the post-transplant setting. Differentiation between the two products is needed to clarify what appear to be conflicting results of the studies presented in this review.View original paper by Posadas Salas and Srinivas

  17. Once-daily indacaterol versus twice-daily salmeterol for COPD: a placebo-controlled comparison.

    Science.gov (United States)

    Kornmann, O; Dahl, R; Centanni, S; Dogra, A; Owen, R; Lassen, C; Kramer, B

    2011-02-01

    Indacaterol is a novel, inhaled, once-daily, ultra-long-acting β(2)-agonist bronchodilator recently approved in Europe for the treatment of chronic obstructive pulmonary disease (COPD). The aim of the present study was to investigate the efficacy and safety of indacaterol compared with placebo and the twice-daily β(2)-agonist, salmeterol, as an active control. Patients with moderate-to-severe COPD were randomised to 6 months double-blind treatment with indacaterol (150 μg once daily), salmeterol (50 μg twice daily) or placebo. The primary efficacy end-point was trough (24 h post-dose) forced expiratory volume in 1 s (FEV(1)) after 12 weeks. 1,002 patients were randomised and 838 (84%) completed the study. Indacaterol increased trough FEV(1) at week 12 by 170 mL over placebo (pindacaterol. Safety profiles were similar across the treatment groups, and both indacaterol and salmeterol were well tolerated. Once-daily treatment with 150 μg indacaterol had a significant and clinically relevant bronchodilator effect over 24 h post-dose and improved health status and dyspnoea to a greater extent than twice-daily 50 μg salmeterol. Indacaterol should prove a useful additional treatment for patients with COPD.

  18. Once-daily dosing of amikacin for treatment of Mycobacterium abscessus lung disease.

    Science.gov (United States)

    Lee, H; Sohn, Y M; Ko, J Y; Lee, S-Y; Jhun, B W; Park, H Y; Jeon, K; Kim, D H; Kim, S-Y; Choi, J E; Moon, I J; Shin, S J; Park, H J; Koh, W-J

    2017-07-01

    Tertiary referral centre, Samsung Medical Center, South Korea. To evaluate the pharmacokinetic parameters and toxicities of once-daily amikacin (AMK) dosing for lung disease due to Mycobacterium abscessus. A retrospective review of 48 patients with M. abscessus lung disease who received once-daily AMK for 4 weeks between January 2012 and June 2015. With a starting dose of 15 mg/kg/day and adjustment of AMK dose according to the peak serum level (Cmax), the Cmax target of 55-65 μg/ml was achieved in 31.3% (15/48) of patients in the first week, 68.8% (33/48) in week 2, 91.7% (44/48) in week 3 and 95.8% (46/48) in week 4. Transient nephrotoxicity developed in 6.3% (3/48) of patients and ototoxicity in 25.0% (6/24), which was determined by audiogram as hearing loss, asymptomatic in five patients and tinnitus in one. Multivariate analysis revealed that the highest drug concentration 12 h after administration was significantly associated with the development of toxicities (adjusted odds ratio 1.862, P = 0.047). Our results suggest that once-daily AMK for 4 weeks with a target Cmax of 55-65 μg/ml can be used in patients with M. abscessus lung disease, with careful monitoring of toxicity.

  19. Tadalafil once daily in the management of erectile dysfunction: patient and partner perspectives

    Directory of Open Access Journals (Sweden)

    Pierre Costa

    2009-04-01

    Full Text Available Pierre Costa1, Thierry Grivel2, Naji Gehchan31Service d’Urologie–Andrologie, Hôpital Caremeau, Nîmes, France; 2159, Avenue Sainte-Marguerite, Nice, France; 3Eli Lilly and Company, Lilly France – Medical Division, Suresnes, FranceAbstract: Erectile dysfunction (ED is a prevalent condition that affects men and their partners. Significant improvements in the sexual lives of these couples have been achieved with the introduction of phosphodiesterase 5 (PDE5 inhibitors. A PDE5 inhibitor is now widely recognized as the first-line therapy for the majority of men with ED. Currently, three PDE5 inhibitors – sildenafil, tadalafil and vardenafil – are approved to be taken as needed in anticipation of sexual activity, but only one of these, tadalafil, has been approved to be taken once daily. The primary aims of this review are to summarize the patients’ and partners’ viewpoints of ED management with PDE5 inhibitors, and to determine whether once-daily tadalafil can contribute to improving some psychological aspects of ED (such as sexual self-confidence, spontaneity and time concerns compared with on-demand tadalafil or other PDE5 inhibitors taken by patients with ED.Keywords: erectile dysfunction, once-daily treatment, patient and partner perspectives, phosphodiesterase 5 (PDE5 inhibitor

  20. Short Communication: Maraviroc Once-Daily: Experience in Routine Clinical Practice.

    Science.gov (United States)

    Saumoy, Maria; Llibre, Josep M; Terrón, Alberto; Knobel, Hernando; Arribas, José Ramón; Domingo, Pere; Arroyo-Manzano, David; Rivero, Antonio; Moreno, Santiago; Podzamczer, Daniel

    2017-01-01

    To assess the efficacy and safety of maraviroc (MVC) administered once-daily in routine clinical practice. A retrospective multicenter study (27 centers in Spain) was conducted. Data were collected from the records of patients starting a regimen with MVC. Laboratory and clinical data were recorded every 3 months the first year and every 6 months thereafter. Data are presented as median and interquartile range. Among 667 patients treated with MVC, 142 (21.3%) received MVC once-daily: 108 (76.1%), 150 mg and 34 (23.9%), and 300 mg. Age was 47 (42-45) years, there were 76.1% men, and 81 (57%) patients had baseline HIV-RNA MVC: salvage therapy (36.6%), drug toxicity (31.2%), simplification (16.9%), and immunodiscordant response (7.1%). Median follow-up was 13 (9-16) months. In 95.8%, a PI/r was part of the regimen (67% on dual therapy). At months 12 and 24, 73.3% and 68.2% of patients had HIV-RNA MVC: virologic failure (6), medical decision (5), and other reasons (14). Two patients presented grade 3 adverse events (hypertransaminasemia, hypertriglyceridemia) without the need for MVC withdrawal, whereas MVC was discontinued in two patients due to gastrointestinal toxicity. In routine clinical practice, MVC once-daily combined with at least PI/r was virologically effective and well tolerated in a high percentage of pretreated patients.

  1. Zaditen SRO permits once-daily dosing with superior efficacy in the prophylaxis of asthma.

    Science.gov (United States)

    Radielovic, P; Morley, J; Hansel, T T; Medici, T C

    1995-01-01

    This international, multicenter clinical trial was designed to compare the efficacy and safety of two different formulations of ketotifen: Zaditen SRO and Zaditen Standard Form. In a randomized double-blind study over a 12-week treatment period, 3 parallel groups of asthmatic subjects received Zaditen SRO (2 mg once daily), Zaditen SRO (4 mg once daily), or Zaditen Standard Form (1 mg twice daily). Asthmatic subjects (362 evaluable cases, aged 6-29 years) kept daily records of clinical symptoms, use of concomitant medication, and peak flow recordings and were examined at 2-week intervals up to the end of the study. Zaditen SRO 4 mg administered once a day at night showed a statistically significant faster onset of action and was more clinically effective than Zaditen Standard Form. The Zaditen SRO 4-mg and 2-mg formulations were at least as well tolerated as the standard form, with somnolence occurring equally after both formulations. In conclusion, Zaditen SRO (4 mg once daily) was found to be equally safe and more effective in the prophylactic treatment of mild and moderate bronchial asthma than Zaditen Standard Form (1 mg twice daily).

  2. Clinical Pharmacokinetics of Once-Daily Tacrolimus in Solid-Organ Transplant Patients.

    Science.gov (United States)

    Staatz, Christine E; Tett, Susan E

    2015-10-01

    Tacrolimus is a pivotal immunosuppressant agent used in solid-organ transplantation. It was originally formulated for oral administration as Prograf(®), a twice-daily immediate-release capsule. In an attempt to improve patient adherence, retain manufacturer market share and/or reduce health care costs, newer once-daily prolonged-release formulations of tacrolimus (Advagraf(®) and Envarsus(®) XR) and various generic versions of Prograf(®) are becoming available. Tacrolimus has a narrow therapeutic index. Small variations in drug exposure due to formulation differences can have a significant impact on patient outcomes. The aim of this review is to critically analyse the published data on the clinical pharmacokinetics of once-daily tacrolimus in solid-organ transplant patients. Forty-three traditional (non-compartmental) and five population pharmacokinetic studies were identified and evaluated. On the basis of the stricter criteria for narrow-therapeutic-index drugs, Prograf(®), Advagraf(®) and Envarsus(®) XR are not bioequivalent [in terms of the area under the concentration-time curve from 0 to 24 h (AUC0-24) or the minimum concentration (C min)]. Patients may require a daily dosage increase if converted from Prograf(®) to Advagraf(®), while a daily dosage reduction appears necessary for conversion from Prograf(®) to Envarsus(®) XR. Prograf(®) itself, or generic immediate-release tacrolimus, can be administered in a once-daily regimen with a lower than double daily dose being reported to give 24-h exposure equivalent to that of a twice-daily regimen. Intense clinical and concentration monitoring is prudent in the first few months after any conversion to once-daily tacrolimus dosing; however, there is no guarantee that therapeutic drug monitoring strategies applicable to one formulation (or twice-daily dosing) will be equally applicable to another. The correlation between the tacrolimus AUC0-24 and C min is variable and not strong for all three

  3. A once-daily HAART regimen containing indinavir + ritonavir plus one or two nucleoside reverse transcriptase inhibitors (PIPO study).

    NARCIS (Netherlands)

    Burger, D.M.; Aarnoutse, R.E.; Dieleman, J.P.; Gyssens, I.C.J.; Nouwen, J.; Marie, S. de; Koopmans, P.P.; Stek Jr, M.; Ende, M.E. van der

    2003-01-01

    INTRODUCTION: There is an increased interest in developing once-daily regimens for the treatment of HIV-infected patients. A Phase II study was conducted to investigate the pharmacokinetics, and short-term safety and efficacy of an indinavir/ritonavir combination as part of a once-daily regimen. MET

  4. Randomized, double-blind, multicenter evaluation of pramipexole extended release once daily in early Parkinson's disease.

    Science.gov (United States)

    Hauser, Robert A; Schapira, Anthony H V; Rascol, Olivier; Barone, Paolo; Mizuno, Yoshikuni; Salin, Laurence; Haaksma, Monika; Juhel, Nolwenn; Poewe, Werner

    2010-11-15

    The objective of this study was to evaluate the efficacy and safety of pramipexole extended release (ER) administered once daily in early Parkinson's disease (PD). Pramipexole immediate release (IR) administered three times daily (TID) is an efficacious and generally well-tolerated treatment for PD. A pramipexole ER formulation is now available. We performed a randomized, double-blind, placebo and active comparator-controlled trial in subjects with early PD. The primary efficacy and safety evaluation of pramipexole ER compared with placebo took place at week 18. Two hundred fifty-nine subjects were randomized 2:2:1 to treatment with pramipexole ER once daily, pramipexole IR TID, or placebo. Levodopa rescue was required by 7 subjects in the placebo group (14%), 3 subjects in the pramipexole ER group (2.9%, P = 0.0160), and 1 subject in the pramipexole IR group (1.0%, P = 0.0017). Adjusted mean [standard error (SE)] change in Unified Parkinson Disease Rating Scale (UPDRS) II [activities of daily living (ADL)] + III (motor) scores from baseline to week 18, including post-levodopa rescue evaluations, was -5.1 (1.3) in the placebo group, -8.1 (1.1) in the pramipexole ER group (P = 0.0282), and -8.4 (1.1) in the pramipexole IR group (P = 0.0153). Adjusted mean (SE) change in UPDRS ADL + motor scores, censoring post-levodopa rescue data, was -2.7 (1.3) in the placebo group, -7.4 (1.1) in the pramipexole ER group (P = 0.0010), and -7.5 (1.1) in the pramipexole IR group (P = 0.0006). Adverse events more common with pramipexole ER than placebo included somnolence, nausea, constipation, and fatigue. Pramipexole ER administered once daily was demonstrated to be efficacious compared with placebo and provided similar efficacy and tolerability as pramipexole IR administered TID.

  5. Efficacy and safety of ciclesonide once daily and fluticasone propionate twice daily in children with asthma

    DEFF Research Database (Denmark)

    Pedersen, Søren; Engelstätter, Renate; Weber, Hans-Jochen

    2009-01-01

    the efficacy and safety of ciclesonide with fluticasone propionate in children with mainly moderate and severe persistent asthma. METHODS: Seven hundred and forty-four patients (aged 6-11years) were randomized to ciclesonide (80 or 160mug once daily) or fluticasone propionate (88mug twice daily), following a 2...... excretion, in children with moderate and severe asthma.......BACKGROUND: Ciclesonide is a new inhaled corticosteroid (ICS). Information about its clinical efficacy and safety in relation to other ICS in children is needed for clinical positioning. OBJECTIVE: This 12-week, randomized, double-blind, double-dummy, three-arm, parallel-group study compared...

  6. [Effectiveness of new, once-daily 5-aminosalicylic acid in the treatment of ulcerative colitis].

    Science.gov (United States)

    Lakatos, Péter László; Lakatos, László

    2009-03-01

    5-aminosalicylate (5-ASA) agents remain the mainstay treatment in ulcerative colitis (UC). A number of oral 5-ASA agents is commercially available, including azo-bond pro-drugs such as sulfasalazine, olsalazine and balsalazide, and delayed- and controlled-release forms of mesalazine. In addition, the effectiveness of oral therapy relies on good compliance, which may be adversely affected by frequent daily dosing and a large number of tablets. Furthermore, poor adherence has been shown to be an important barrier to successful management of patients with UC. Recently, new, once-daily formulations of mesalazine including the unique multi-matrix delivery system and mesalazine granules were proven to be efficacious in inducing and maintaining remission in mild-to-moderate UC, with a good safety profile comparable to that of other oral mesalazine formulations. In addition, they offer the advantage of low pill burden and may contribute to increased long-term compliance and treatment success in clinical practice and might potentially further contribute to a decline in the risk for UC-associated colon cancers. In this systematic review, the authors summarize the available literature on the short- and medium-term efficacy and safety of the new once-daily mesalazine formulations.

  7. Once daily 5-aminosalicylic acid for the treatment of ulcerative colitis; are we there yet?

    Science.gov (United States)

    Lakatos, Peter Laszlo; Lakatos, Laszlo

    2008-01-01

    5-Aminosalicylate (5-ASA) agents remain the mainstay treatment in ulcerative colitis (UC). A number of oral 5-ASA agents are commercially available, including azo-bond pro-drugs such as sulfasalazine, olsalazine and balsalazide, and delayed- and controlled-release forms of mesalazine. In addition, the effectiveness of oral therapy relies on good compliance, which may be adversely affected by frequent daily dosing and a large number of tablets. Furthermore, poor adherence has been shown to be an important barrier to successful management of patients with UC. Recently, new, once daily formulations of mesalazine including the unique multi-matrix delivery system and mesalazine granules were proven to be efficacious in inducing and maintaining remission in mild-to-moderate UC, with a good safety profile comparable to that of other oral mesalazine formulations. In addition, they offer the advantage of low pill burden and may contribute to increased long-term compliance and treatment success in clinical practice and might potentially further contribute to a decline in the risk for UC-associated colon cancers. In this systematic review, the authors summarize the available literature on the short- and medium-term efficacy and safety of the new once daily mesalazine formulations.

  8. Effects of Converting Tacrolimus Formulation from Twice-Daily to Once-Daily in Liver Transplantation Recipients

    Directory of Open Access Journals (Sweden)

    Ashok Thorat

    2014-01-01

    Full Text Available Typically, tacrolimus is administrated twice daily. Prolonged-release tacrolimus is the once-daily formulation and may be more convenient for patients. Experience with the administration of the once-daily formulation is still limited. This study enrolled 210 liver transplant recipients who had stable liver function and converted tacrolimus from a twice-daily to once-daily formulation on a 1 mg to 1 mg basis. Among 210 patients, seven patients (3.3% were withdrawn from the once-daily formulation due to allergy and fatigue. For the other patients, the trough concentration after converting to the once-daily formulation was lower than that of the twice-daily formulation. Liver enzymes were mildly elevated in 3 months after formulation conversion and serum creatinine and uric acid were mildly decreased. Seven patients (3.4% had clinical suspicion of acute rejection after the formulation conversion and three of them were caused by nonadherence. 155 patients (76.4% experienced a more convenient life with an increase of social activity. Forty-seven patients (23.2% experienced the convenience of once-daily formulation during overseas trips. In conclusion, tacrolimus can be safely converted from the twice-daily to the once-daily formulation for most stable liver recipients. Acute rejection may occur in a minority of patients during formulation conversion and should be carefully monitored.

  9. Randomised trial of once-daily vilanterol in children with asthma on inhaled corticosteroid therapy.

    Science.gov (United States)

    Oliver, Amanda J; Covar, Ronina A; Goldfrad, Caroline H; Klein, Ryan M; Pedersen, Søren E; Sorkness, Christine A; Tomkins, Susan A; Villarán, César; Grigg, Jonathan

    2016-04-05

    Inhaled corticosteroids (ICS) are effective maintenance treatments for childhood asthma; however, many children remain uncontrolled. Vilanterol (VI) is an inhaled long-acting beta-2 agonist which, in combination with the ICS fluticasone furoate, is being explored as a once-daily treatment for asthma in children. We evaluated the dose-response, efficacy, and safety of once-daily VI (6.25 μg, 12.5 μg and 25 μg) administered in the evening over 4 weeks, on background fluticasone propionate (FP) in children with asthma inadequately controlled on ICS. This was a Phase IIb, multicentre, randomised, double-blind, parallel-group, placebo-controlled study in children ages 5-11 years with persistent asthma on ICS and as-needed short-acting beta-agonist. The study comprised a 4-week run-in, 4-week treatment period, and 1-week follow-up. From study start, children replaced their current ICS with open-label FP 100 μg twice daily. Children were randomised to receive placebo, VI 6.25 μg, VI 12.5 μg or VI 25 μg once daily. Primary endpoint was treatment difference between VI 25 and placebo groups in mean change from baseline in evening peak expiratory flow averaged over the 4-week treatment. Secondary endpoints included change from baseline in trough forced expiratory volume in one second (FEV1) at Week 4 and change from baseline in percentage of rescue-free and symptom-free 24-h periods. Safety assessments included incidence of adverse events (AEs) and asthma exacerbations. In total, 456 children comprised the intention-to-treat population. The adjusted treatment difference between VI 25 and placebo groups for the primary endpoint was not statistically significant (p = 0.227) so no statistical inference was made for other VI dose comparisons or other endpoints. No difference in change from baseline in trough FEV1 was observed for any VI treatments versus placebo; however, VI 25 resulted in an additional 0.6 rescue-free days and 0.7 symptom-free days per week versus

  10. 78 FR 46965 - Draft Guidance for Industry on Bioequivalence Recommendations for Mesalamine Rectal Suppositories...

    Science.gov (United States)

    2013-08-02

    ... Recommendations for Mesalamine Rectal Suppositories; Availability AGENCY: Food and Drug Administration, HHS... applications (ANDAs) for mesalamine rectal suppositories. The draft guidance is a revised version of a... on mesalamine (Draft Mesalamine Rectal Suppository BE Recommendations of 2013). CANASA (Mesalamine...

  11. Liraglutide: a once-daily GLP-1 analogue for the treatment of type 2 diabetes mellitus

    DEFF Research Database (Denmark)

    Vilsbøll, Tina

    2007-01-01

    The incretin hormones are intestinal peptides that enhance insulin secretion following ingestion of nutrients. Liraglutide is a glucagon-like peptide-1 receptor analogue, which is obtained by derivatising glucagon-like peptide-1 with a fatty acid, providing a compound with pharmacokinetic propert...... transient nausea and diarrhoea. This article reviews the mechanisms of action and efficacy of liraglutide for the treatment of Type 2 diabetes mellitus. This agent is presently in Phase III clinical development....... properties that are suitable for once-daily dosing. Liraglutide has demonstrated lasting improvement of HbA(1c )levels, weight reduction and improved beta-cell function in patients with Type 2 diabetes mellitus. Liraglutide is well tolerated; the adverse events that are most frequently reported being...

  12. Efficacy of Tadalafil once daily versus Fesoterodine in the treatment of overactive bladder in older patients.

    Science.gov (United States)

    Dell'Atti, L

    2015-01-01

    Several studies have suggested that phosphodiesterase type 5 inhibitors (5-PDEi) show a potential therapeutic use in the treatment of overactive bladder (OAB) and male lower urinary tract symptoms (LUTS). The aim of this study was to evaluating the efficacy on OAB symptoms, impact on quality of life and sexual function of tadalafil 5mg once daily in older patients versus fesoterodine 8 mg. 108 consecutive patients diagnosed with OAB were divided into 2 groups: Group A: 56 patients treated with tadalafil 5 mg once daily; Group B: 52 patients treated with fesoterodine 8 mg, both groups treated for a period of 12 weeks. Eligible patients were men aged ≥ 65 years with OAB symptoms, including urgency and increased frequency during a period of ≥ 1 year and urgency urinary incontinence during a period of ≥ 6 months before enrolment. Patients were asked to complete the 3-day voiding diary prior each scheduled visit at weeks 0, 4 and 12. During these visits, they were administered: Overactive Bladder Symptom Score (OABSS), International Prostate Symptoms Score (IPSS), International Index of Erectile Function (IIEF-5) and Quality of life (QoL). Not statistically significant differences emerged between the two groups at baseline, both patient groups had similar age and BMI; in each treatment group, the proportion of men ≥ 75 years was approximately 65%. From the results of our study, we can say that a treatment once a day with tadalafil improves not only significantly: micturition/24 hours (p fesoterodine treatment, but also the quality of life (p fesoterodine 8 mg is efficacious in the treatment of the symptoms of OAB in older adults, improving also the quality of life and sexual and social life.

  13. Multiple dose pharmacokinetics of a new once daily extended release tolterodine formulation versus immediate release tolterodine.

    Science.gov (United States)

    Olsson, B; Szamosi, J

    2001-01-01

    To determine the multiple dose pharmacokinetics of a new extended release (ER) capsule formulation of tolterodine, compared with the existing immediate release (IR) tablet, in healthy volunteers. Nonblind, randomised, 2-way crossover trial. 19 healthy volunteers (7 females, 12 males), mean age 33 years (range 18 to 55 years). Prior to the study, all volunteers were classified as either extensive or poor metabolisers by cytochrome P450 2D6 genotyping. Volunteers received tolterodine ER 4mg once daily or tolterodine IR 2mg twice daily for 6 days (all doses given as the L-tartrate salt). A washout period of 7 days separated the 2 treatments. Serum concentrations of tolterodine, its active 5-hydroxymethyl metabolite (5-HM) and the active moiety (extensive metabolisers: sum of unbound tolterodine + 5-HM; poor metabolisers: unbound tolterodine) were measured for up to 48 hours post-dose on day 6 (steady state). Tolerability was also determined. 17 volunteers (13 extensive metabolisers, 4 poor metabolisers) completed the study and were evaluable for both treatment periods. The 90% confidence interval for the geometric mean ratio of area under the serum concentration-time curve to 24 hours (AUC24) of the active moiety, for all volunteers combined, indicated equivalence for the 2 formulations. Pooled analysis also demonstrated that the peak serum concentration (Cmax) of the active moiety following administration of tolterodine ER was around 75% of that observed for the IR tablet, whereas the trough concentration was around 1.5-fold higher. Overall, the pharmacokinetics of tolterodine (irrespective of genotype) and 5-HM (extensive metabolisers only) were consistent with sustained drug release over 24 hours. Tolterodine ER was well tolerated. The new once daily ER formulation of tolterodine 4mg shows pharmacokinetic equivalence (AUC24) to the existing IR tablet given at a dose of 2mg twice daily. Findings of lower Cmax for tolterodine ER may explain the significantly lower

  14. FULFIL Trial: Once-Daily Triple Therapy for Patients with Chronic Obstructive Pulmonary Disease.

    Science.gov (United States)

    Lipson, David A; Barnacle, Helen; Birk, Ruby; Brealey, Noushin; Locantore, Nicholas; Lomas, David A; Ludwig-Sengpiel, Andrea; Mohindra, Rajat; Tabberer, Maggie; Zhu, Chang-Qing; Pascoe, Steven J

    2017-08-15

    Randomized data comparing triple therapy with dual inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA) therapy in patients with chronic obstructive pulmonary disease (COPD) are limited. We compared the effects of once-daily triple therapy on lung function and health-related quality of life with twice-daily ICS/LABA therapy in patients with COPD. The FULFIL (Lung Function and Quality of Life Assessment in Chronic Obstructive Pulmonary Disease with Closed Triple Therapy) trial was a randomized, double-blind, double-dummy study comparing 24 weeks of once-daily triple therapy (fluticasone furoate/umeclidinium/vilanterol 100 μg/62.5 μg/25 μg; ELLIPTA inhaler) with twice-daily ICS/LABA therapy (budesonide/formoterol 400 μg/12 μg; Turbuhaler). A patient subgroup remained on blinded treatment for up to 52 weeks. Co-primary endpoints were change from baseline in trough FEV1 and in St. George's Respiratory Questionnaire (SGRQ) total score at Week 24. In the intent-to-treat population (n = 1,810) at Week 24 for triple therapy (n = 911) and ICS/LABA therapy (n = 899), mean changes from baseline in FEV1 were 142 ml (95% confidence interval [CI], 126 to 158) and -29 ml (95% CI, -46 to -13), respectively, and mean changes from baseline in SGRQ scores were -6.6 units (95% CI, -7.4 to -5.7) and -4.3 units (95% CI, -5.2 to -3.4), respectively. For both endpoints, the between-group differences were statistically significant (P < 0.001). There was a statistically significant reduction in moderate/severe exacerbation rate with triple therapy versus dual ICS/LABA therapy (35% reduction; 95% CI, 14-51; P = 0.002). The safety profile of triple therapy reflected the known profiles of the components. These results support the benefits of single-inhaler triple therapy compared with ICS/LABA therapy in patients with advanced COPD. Clinical trial registered with www.clinicaltrials.gov (NCT02345161).

  15. Among once-daily regimens, single tablet regimens (STRs are associated with better adherence

    Directory of Open Access Journals (Sweden)

    R Murri

    2012-11-01

    Full Text Available Previous published evidences showed that taking HAART once-daily (OD is associated to better adherence when compared to BID or TID regimens. However, no further studies investigated whether, among OD regimens, adherence levels can be differently influenced. Aim of the study was to evaluate levels of self-reported adherence in HIV+ people according to type of HAART dosing (STR, OD with more than one pill or BID. To limit reporting biases, the study was performed in five different non-clinic settings covering North and Central Italy. A total of 230 patients on stable HAART were asked to complete a semi-structured, anonymous questionnaire reporting their attitude toward HAART, their adherence and the acceptability of their regimen. Self-perception of adherence was also investigated with a single item for comparison with real adherence behavior. Most of the subjects were males (66% with a mean age of 46 years, with higher education level (72% and a long history of HIV infection (mean 13.6 years. 17% of patients were on a first-line regimen. 21% reported to miss at least one dose during the past week (STR: 6%; OD >1 pill 23% and BID 21%; p<0.05. People taking STR and BID tend to report less discontinuations (all the drug of the day for at least 3 times in a month compared to OD>1 pill (6 and 4% vs 11%. People taking therapies other than HAART reported similar adherence levels of people taking only HAART, even when stratified for dosing groups. Even people judging their adherence as ‘optimal’ or ‘very good’, 10 and 17% respectively, reported having missed a dose during the last week. At stepwise regression model, optimal adherence was correlated to being male (OR: 2.38; 95% CI: 1.19–4.74, younger (OR: 3.04; 95% CI: 1.01–9.13 and with a shorter HIV infection (OR: 3.58; 95% CI: 1.04–12.38. People taking simpler once-daily STR tend to report better adherence than people taking OD>1 pill or BID. Perception of optimal adherence is largely

  16. Effect of alfaprostol, lasalocid, and once-daily suckling on postpartum interval in Brahman and Brahman crossbred cattle.

    Science.gov (United States)

    Del Vecchio, R P; Randel, R D; Neuendorff, D A; Peterson, L A

    1988-10-01

    Brahman cows (n = 49) and primiparous heifers (n = 11), Brahman x Hereford primiparous F1 heifers (n = 86) and Simmental x Brahman primiparous F1 heifers (n = 13) were randomly allotted by breed, age and date of calving to one of eight treatment groups: 1) control; 2) once-daily suckling; 3) lasalocid (200 mg/hd/d); 4) alfaprostol (5 mg intermuscular injections on Days 21 and 32 post partum); 5) lasalocid + once-daily suckling; 6) alfaprostol + once daily suckling; 7) alfaprostol + lasalocid; 8) alfaprostol + lasalocid + once daily suckling. All animals received 2.3 kg/hd/d of a concentrate (6 corn : 1 cottonseed meal) and lasalocid was mixed and fed in the concentrate. Body weights and condition scores were taken on Day 1 post partum and every 28 d thereafter. All animals were maintained with sterile marker bulls with Brahman and Simmental x Brahman cattle artificially inseminated at first estrus. Blood samples were collected at weekly intervals starting on Day 21 post partum until estrus and at nine to twelve days post estrus when the ovaries were palpated for corpora lutea. After the first postpartum estrus with a corpora lutea, cows were placed with fertile bulls. Mean serum progesterone concentrations were below 0.5 ng/ml prior to treatment. Calf weight gains to 90 d were not affected by age (P > 0.10) but were lower in the once-daily suckling group (P 0.10). Cows had a shorter postpartum interval (P 0.10) but did increase the cumulative frequency of return to estrus by 90 d post partum (P 0.10). Both once-daily suckling and alfaprostol were effective in increasing the numbers of animals inseminated by 90 d post partum. The once-daily suckling + alfaprostol treatment resulted in the shortest postpartum interval.

  17. Efficacy and safety of once-daily aclidinium in chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Bateman Eric D

    2011-04-01

    Full Text Available Abstract Background The long-term efficacy and safety of aclidinium bromide, a novel, long-acting muscarinic antagonist, were investigated in patients with moderate to severe chronic obstructive pulmonary disease (COPD. Methods In two double-blind, 52-week studies, ACCLAIM/COPD I (n = 843 and II (n = 804, patients were randomised to inhaled aclidinium 200 μg or placebo once-daily. Patients were required to have a post-bronchodilator forced expiratory volume in 1 second (FEV1/forced vital capacity ratio of ≤70% and FEV1 1 at 12 and 28 weeks. Secondary endpoints were health status measured by St George's Respiratory Questionnaire (SGRQ and time to first moderate or severe COPD exacerbation. Results At 12 and 28 weeks, aclidinium improved trough FEV1 versus placebo in ACCLAIM/COPD I (by 61 and 67 mL; both p Conclusion Aclidinium is effective and well tolerated in patients with moderate to severe COPD. Trial registration ClinicalTrials.gov: NCT00363896 (ACCLAIM/COPD I and NCT00358436 (ACCLAIM/COPD II.

  18. The emergence of oral tadalafil as a once-daily treatment for pulmonary arterial hypertension

    Directory of Open Access Journals (Sweden)

    Jeremy A Falk

    2010-04-01

    Full Text Available Jeremy A Falk, Kiran J Philip, Ernst R SchwarzCedars Sinai Women’s Guild Lung Institute, Cedars Sinai Heart Institute, Cedars Sinai Medical Center, Los Angeles, CA, USAAbstract: Pulmonary hypertension (PH is found in a vast array of diseases, with a minority representing pulmonary arterial hypertension (PAH. Idiopathic PAH or PAH in association with other disorders has been associated with poor survival, poor exercise tolerance, progressive symptoms of dyspnea, and decreased quality of life. Left untreated, patients with PAH typically have a progressive decline in function with high morbidity ultimately leading to death. Advances in medical therapy for PAH over the past decade have made significant inroads into improved function, quality of life, and even survival in this patient population. Three classes of pulmonary artery-specific vasodilators are currently available in the United States. They include prostanoids, endothelin receptor antagonists, and phosphodiesterase type 5 (PDE5 inhibitors. In May 2009, the FDA approved tadalafil, the first once-daily PDE5 inhibitor for PAH. This review will outline the currently available data on tadalafil and its effects in patients with PAH.Keywords: PDE-5 inhibition, pulmonary hypertension, tadalafil

  19. Tafluprost once daily for treatment of elevated intraocular pressure in patients with open-angle glaucoma

    Directory of Open Access Journals (Sweden)

    Liu Y

    2012-12-01

    Full Text Available Yang Liu, Weiming MaoDepartment of Cell Biology and Anatomy, North Texas Eye Research Institute, University of North Texas Health Science Center, Fort Worth, TXAbstract: Glaucoma is a leading cause of visual loss worldwide. Current antiglaucoma therapy focuses on lowering intraocular pressure to a safe level. In recent years, prostaglandin analogs have become the first-line agents for treating open angle glaucoma. Tafluprost, which was first reported in 2003, is a novel prostaglandin analog, and has been shown to be a potent ocular hypotensive agent in a number of preclinical and clinical studies. Also, its unique preservative-free formulation helps to decrease preservative-associated ocular disorders and improve patient compliance. In this review, studies from 2003 to 2012 focusing on the structure, metabolism, efficacy, and safety of tafluprost are summarized. These studies suggested that application of tafluprost once daily is a safe and effective treatment for patients with open angle glaucoma.Keywords: tafluprost, prostaglandin analog, glaucoma, intraocular pressure, preservative-free formulation

  20. Randomized Trial of Once-Daily Fluticasone Furoate in Children with Inadequately Controlled Asthma

    DEFF Research Database (Denmark)

    Oliver, Amanda J.; Covar, Ronina A.; Goldfrad, Caroline H.

    2016-01-01

    Objective To evaluate the dose-response, efficacy, and safety of fluticasone furoate (FF; 25 µg, 50 µg, and 100 µg), administered once daily in the evening during a 12-week treatment period to children with inadequately controlled asthma. Study design This was a Phase IIb, multicenter, stratified......, randomized, double-blind, double-dummy, parallel-group, placebo- and active-controlled study in children aged 5-11 years with inadequately controlled asthma. The study comprised a 4-week run-in period, 12-week treatment period, and 1-week follow-up period. Children were randomized to receive either placebo...... In total, 593 children were included in the intent-to-treat population. The difference vs placebo in change from baseline daily morning PEF averaged over weeks 1-12 was statistically significant for the FF 25, FF 50, FF 100, and FP 100 groups (18.6 L/min, 19.5 L/min, 12.5 L/min, and 14.0 L...

  1. Blinded 12-week comparison of once-daily indacaterol and tiotropium in COPD.

    Science.gov (United States)

    Buhl, R; Dunn, L J; Disdier, C; Lassen, C; Amos, C; Henley, M; Kramer, B

    2011-10-01

    Two, once daily (q.d.) inhaled bronchodilators are available for the treatment of chronic obstructive pulmonary disease (COPD): the β(2)-agonist indacaterol and the anticholinergic tiotropium. This blinded study compared the efficacy of these two agents and assessed their safety and tolerability. Patients with moderate-to-severe COPD were randomised to treatment with indacaterol 150 μg q.d. (n=797) or tiotropium 18 μg q.d. (n=801) for 12 weeks. After 12 weeks, the two treatments had similar overall effects on "trough" (24 h post-dose) forced expiratory volume in 1 s. Indacaterol-treated patients had greater improvements in transition dyspnoea index (TDI) total score (least squares means 2.01 versus 1.43; pindacaterol versus tiotropium odds ratios of 1.49 for TDI and 1.43 for SGRQ, both pindacaterol and tiotropium treatment groups, respectively. The most frequent adverse events were COPD worsening, cough and nasopharyngitis. Both bronchodilators demonstrated spirometric efficacy. The two treatments were well tolerated with similar adverse event profiles. Compared with tiotropium, indacaterol provided significantly greater improvements in clinical outcomes.

  2. Formulation and evaluation of once daily minocycline hydrochloride extended release matrix tablets

    Directory of Open Access Journals (Sweden)

    Keny R

    2009-01-01

    Full Text Available The present study was aimed to develop once daily extended release matrix tablets of minocycline hydrochloride, using hydroxypropylmethylcellulose either alone or in combination with ethyl cellulose as the matrix material in different proportions. The formulated tablets were also compared with a marketed product. The results of the dissolution study indicate that formulations FC-IV, FC-V and FC-VI showed maximum drug release upto 24 h, whereas the marketed product was found to extend the release only up to 14 h. Incase of formulations containing combination of hydroxypropylmethylcellulose and ethyl cellulose (FC-I to FC-IX, the release of the drug was found to be dependent on the relative proportions of hydroxypropylmethylcellulose and ethyl cellulose used in the tablet matrix. Mathematical treatment of the in vitro drug release data suggests that, all the formulations best fitted into first order release kinetics. Drug release from the matrix occurred by combination of two mechanisms, diffusion of drug from tablet matrix and erosion of tablet surface, which was reflected from Higuchi′s model and Erosion plot.

  3. Evaluation of once daily treatment with cyclosporine for anal furunculosis in dogs.

    Science.gov (United States)

    Doust, R; Griffiths, L G; Sullivan, M

    2003-02-22

    Twenty-four dogs with anal furunculosis were treated with cyclosporine once daily for 13 weeks at dosages of 1.5, 3.0, 5.0 or 7.5 mg/kg, and re-examined after six and 12 months. After 13 weeks the disease in six of the dogs was in remission, 11 were controlled or improved and seven had failed to respond. The response of the dogs given the highest dose was significantly better than the response of the other groups taken together (P dogs improved clinically during the treatment, most rapidly during the first five weeks. Of the six dogs that were in remission after 13 weeks, three relapsed after one, two and six months. The 11 dogs that were improved or controlled after 13 weeks were either left untreated or were continued on cyclosporine medication for one to three months at a dosage of 1.5 to 7.5 mg/kg; the disease went into remission in four cases and remained controlled in the other seven, but four of the 11 cases relapsed during the 12 months following the treatment. The side effects observed included increased coat turnover and transient vomiting.

  4. Distal Ulcerative Colitis Refractory to Rectal Mesalamine: Role of Transdermal Nicotine versus Oral Mesalamine

    OpenAIRE

    Mario Guslandi; Roberto Frego; Edi Viale; Pier Alberto Testoni

    2002-01-01

    BACKGROUND: Distal ulcerative colitis usually responds to treatment with rectal mesalamine, but the management of refractory cases is poorly defined.AIM: To evaluate the possible therapeutic benefit of transdermal nicotine versus oral mesalamine.PATIENTS AND METHODS: Thirty patients with left-sided ulcerative colitis unresponsive to treatment with a mesalamine 4 g enema at bedtime were randomly allocated to additional therapy with either transdermal nicotine 15 mg daily or oral mesalamine 800...

  5. A once-daily dose of tadalafil for erectile dysfunction: compliance and efficacy

    Directory of Open Access Journals (Sweden)

    Samuel L Washington III

    2010-08-01

    Full Text Available Samuel L Washington III1, Alan W Shindel21School of Medicine, University of California at San Francisco, San Francisco, California, USA; 2Department of Urology, University of California at San Francisco, San Francisco, California, USAAbstract: Selective phosphodiesterase type 5 inhibitors (PDE5Is have revolutionized the ­treatment of erectile dysfunction (ED in men. As an on-demand treatment, PDE5Is have excellent efficacy and safety in the treatment of ED due to a broad spectrum of etiologies. Nevertheless, these drugs do have side-effect profiles that are troublesome to some patients, eg, headache, dyspepsia, myalgia, etc. Furthermore, many patients and their partners dislike the necessity of on-demand treatment for ED, citing a desire for greater spontaneity with sexual interactions. In 2008, approximately 10 years after the release of the first commercially available PDE5I, a paradigm shift in the management of ED occurred with the approval of once-daily dose of tadalafil by the US Food and Drug Administration for the management of ED. The prolonged half-life of tadalafil lends itself well to this dosing regimen and conveys the advantage of separating medication from sexual interactions; lower dose therapy also carries the theoretical benefit of lower incidence of side effects. In this study, we review the current state of the art with respect to this new management strategy for ED, highlighting published reports of the efficacy and tolerability of the daily dose tadalafil regimen.Keywords: PDE5 inhibitor, on-demand therapy, side effects, daily dosing

  6. Twice-Daily versus Once-Daily Pramipexole Extended Release Dosage Regimens in Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Ji Young Yun

    2017-01-01

    Full Text Available This open-label study aimed to compare once-daily and twice-daily pramipexole extended release (PER treatment in Parkinson’s disease (PD. PD patients on dopamine agonist therapy, but with unsatisfactory control, were enrolled. Existing agonist doses were switched into equivalent PER doses. Subjects were consecutively enrolled into either once-daily-first or twice-daily-first groups and received the prescribed amount in one or two, respectively, daily doses for 8 weeks. For the second period, subjects switched regimens in a crossover manner. The forty-four patients completed a questionnaire requesting preference during their last visit. We measured the UPDRS-III, Hoehn and Yahr stages (H&Y in medication-on state, Parkinson’s disease sleep scale (PDSS, and Epworth Sleepiness Scale. Eighteen patients preferred a twice-daily regimen, 12 preferred a once-daily regimen, and 14 had no preference. After the trial, 14 subjects wanted to be on a once-daily regimen, 25 chose a twice-daily regimen, and 5 wanted to maintain the prestudy regimen. Main reasons for choosing the twice-daily regimen were decreased off-duration, more tolerable off-symptoms, and psychological stability. The mean UPDRS-III, H&Y, and PDSS were not different. Daytime sleepiness was significantly high in the once-daily regimen, whereas nocturnal hallucinations were more common in the twice-daily. Multiple dosing should be considered if once-daily dosing is unsatisfactory. This study is registered as NCT01515774 at ClinicalTrials.gov.

  7. Isolated fever induced by mesalamine treatment.

    Science.gov (United States)

    Slim, Rita; Amara, Joseph; Nasnas, Roy; Honein, Khalil; Jaoude, Joseph Bou; Yaghi, Cesar; Daniel, Fady; Sayegh, Raymond

    2013-02-21

    Adverse reactions to mesalamine, a treatment used to induce and maintain remission in inflammatory bowel diseases, particularly ulcerative colitis, have been described in the literature as case reports. This case illustrates an unusual adverse reaction. Our patient developed an isolated fever of unexplained etiology, which was found to be related to mesalamine treatment. A 22-year-old patient diagnosed with ulcerative colitis developed a fever with rigors and anorexia 10 d after starting oral mesalamine while his colitis was clinically resolving. Testing revealed no infection. A mesalamine-induced fever was considered, and treatment was stopped, which led to spontaneous resolution of the fever. The diagnosis was confirmed by reintroducing the mesalamine. One year later, this side effect was noticed again in the same patient after he was administered topical mesalamine. This reaction to mesalamine seems to be idiosyncratic, and the mechanism that induces fever remains unclear. Fever encountered in the course of a mesalamine treatment in ulcerative colitis must be considered a mesalamine-induced fever when it cannot be explained by the disease activity, an associated extraintestinal manifestation, or an infectious etiology.

  8. Clinical potential of lixisenatide once daily treatment for type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Petersen AB

    2013-06-01

    Full Text Available Andreas B Petersen,1 Mikkel Christensen1,21Department of Clinical Pharmacology, Bispebjerg Hospital, Copenhagen, Denmark; 2Diabetes Research Division, Department of Internal Medicine, Gentofte Hospital, Copenhagen, DenmarkAbstract: The glucagon-like peptide (GLP-1 receptor agonist lixisenatide (Lyxumia® was approved for marketing by the European Medicines Agency in February 2013 and has been evaluated in a clinical study program called GetGoal. Lixisenatide activates the GLP-1 receptor and thereby exercises the range of physiological effects generated by GLP-1, which consist of increased insulin secretion, inhibition of glucagon secretion, and decreased gastrointestinal motility alongside the promotion of satiety. In the GetGoal study program, lixisenatide demonstrated significant reductions in glycated hemoglobin (HbA1c, and fasting and postprandial plasma glucose compared with placebo. The effect on glycemia was evident, with both monotherapy and in combination with insulin and various oral antidiabetic agents. Furthermore, a general trend towards reduced bodyweight was reported. In head-to-head trials with the other GLP-1 receptor agonists (exenatide and liraglutide on the market, lixisenatide demonstrated a superior effect with respect to reduction in postprandial plasma glucose and had a tendency towards fewer adverse events. However, lixisenatide seemed to be less efficient or at best, equivalent to exenatide and liraglutide in reducing HbA1c, fasting plasma glucose, and bodyweight. The combination of a substantial effect on postprandial plasma glucose and a labeling with once daily administration separates lixisenatide from the other GLP-1 receptor agonists. The combination of basal insulin, having a lowering effect on fasting plasma glucose, and lixisenatide, curtailing the postprandial glucose excursions, makes sense from a clinical point of view. Not surprisingly, lixisenatide is undergoing clinical development as a combination

  9. Fluticasone furoate: once-daily evening treatment versus twice-daily treatment in moderate asthma

    Directory of Open Access Journals (Sweden)

    Woodcock Ashley

    2011-12-01

    Full Text Available Abstract Background Inhaled corticosteroids are the recommended first-line treatment for asthma but adherence to therapy is suboptimal. The objectives of this study were to compare the efficacy and safety of once-daily (OD evening and twice-daily (BD regimens of the novel inhaled corticosteroid fluticasone furoate (FF in asthma patients. Methods Patients with moderate asthma (age ≥ 12 years; pre-bronchodilator forced expiratory volume in 1 second (FEV1 40-85% predicted; FEV1 reversibility of ≥ 12% and ≥ 200 ml were randomized to FF or fluticasone propionate (FP regimens in a double-blind, crossover study. Patients were not permitted to have used any ICS for ≥ 8 weeks prior to enrolment and subsequently received doses of FF or FP 200 μg OD, FF or FP 100 μg BD and matching placebo by inhalation for 28 days each. Primary endpoint was Day 28 evening pre-dose (trough FEV1; non-inferiority of FF 200 μg OD and FF 100 μg BD was assessed, as was superiority of all active treatment relative to placebo. Adverse events (AEs and 24-hour urinary cortisol excretion were assessed. Results The intent-to-treat population comprised 147 (FF and 43 (FP patients. On Day 28, pre-dose FEV1 showed FF 200 μg OD to be non-inferior (pre-defined limit -110 ml to FF 100 μg BD (mean treatment difference 11 ml; 95% CI: -35 to +56 ml; all FF and FP regimens were significantly superior to placebo (p ≤ 0.02. AEs were similar to placebo; no serious AEs were reported. Urinary cortisol excretion at Day 28 for FF was lower than placebo (ratios: 200 μg OD, 0.75; 100 μg BD, 0.84; p ≤ 0.02. Conclusions FF 200 μg OD in the evening is an efficacious and well tolerated treatment for asthma patients and is not inferior to the same total BD dose. Trial registration Clinicaltrials.gov; NCT00766090.

  10. Comparison of once daily versus twice daily olmesartan in patients with chronic kidney disease

    Directory of Open Access Journals (Sweden)

    Sakai Y

    2013-10-01

    Full Text Available Yukinao Sakai,1 Anna Suzuki,1 Koji Mugishima,1 Yuichiro Sumi,1 Yusuke Otsuka,1 Tomoyuki Otsuka,1 Dai Ohno,1 Tsuneo Murasawa,1 Shuichi Tsuruoka21Department of Nephrology, Nippon Medical School Musashikosugi Hospital, Kawasaki, Japan; 2Division of Nephrology, Department of Internal Medicine, Graduate School of Medicine, Nippon Medical School, Tokyo, JapanBackground: The effects of olmesartan (OLM on blood pressure and kidney function in Japanese patients with chronic kidney disease (CKD were compared between 20 mg twice daily (BID and 40 mg once daily (QD treatments.Methods: The subjects were Japanese CKD patients with concurrent hypertension who had been treated with OLM 20 mg BID for at least 3 months on an outpatient basis (n=39. After a change in the treatment regimen to 40 mg OLM QD (after breakfast, blood pressure (BP (n=39, morning home BP (n=13, estimated glomerular filtration rate (n=39, and urinary albumin-to-creatinine ratio (n=17 were monitored for 2 months.Results: No significant change in office (mean ± standard deviation [SD] [mmHg], 143.9 ± 18.8/75.7 ± 12.0 to 141.6 ± 16.1/74.7 ± 11.7, not significant [ns] or early morning home (mean ± SD [mmHg], 133.8 ± 15.9/71.2 ± 11.5 to 133.8 ± 13.9/74.5 ± 10.5, ns BP was observed 2 months after the change in dose. The estimated glomerular filtration rate increased significantly (mean ± SD, 49.0 ± 28.0 to 51.8 ± 27.0, P<0.05, whereas urinary albumin-to-creatinine ratio did not change significantly (mean ± SD, 0.551 ± 0.445 to 0.364 ± 0.5194, ns.Conclusion: High-dose OLM administered BID and QD had similar effects on outpatient and early morning home BP in CKD patients, suggesting that the BID regimen can be safely changed to a QD regimen. For CKD patients with hypertension requiring continuous long-term treatment, the possibility that the QD regimen might bring a greater therapeutic effect was suggested. However, recognizing the best blood pressure control level for a CKD

  11. Adherence and acceptability of once daily Lamivudine and abacavir in human immunodeficiency virus type-1 infected children.

    NARCIS (Netherlands)

    LePrevost, M.; Green, H.; Flynn, J.; Head, S.; Clapson, M.; Lyall, H.; Novelli, V.; Farrelly, L.; Walker, A.S.; Burger, D.M.; Gibb, D.

    2006-01-01

    BACKGROUND: Data on adherence to and acceptability of once daily lamivudine and abacavir are few. METHODS: Twenty-four U.K. human immunodeficiency virus type-1 infected children 2-13 years of age participated in the Pediatric European Network for the Treatment of AIDS (PENTA) 13 single arm, open lab

  12. Randomized clinical trial: pharmacokinetics and safety of multimatrix mesalamine for treatment of pediatric ulcerative colitis

    Directory of Open Access Journals (Sweden)

    Cuffari C

    2016-02-01

    Full Text Available Carmen Cuffari,1 David Pierce,2 Bartosz Korczowski,3 Krzysztof Fyderek,4 Heather Van Heusen,5 Stuart Hossack,6 Hong Wan,5 Alena YZ Edwards,7 Patrick Martin5 1Department of Pediatrics, Division of Pediatric Gastroenterology and Nutrition, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; 2Shire, Basingstoke, UK; 3Medical College, University of Rzeszów, Rzeszów, Poland; 4University Children’s Hospital of Cracow, Cracow, Poland; 5Shire, Wayne, PA, USA; 6Covance Clinical Research Unit Limited, Leeds, UK; 7ICON Early Phase Services, Marlow, Buckinghamshire, UK Background: Limited data are available on mesalamine (5-aminosalicylic acid; 5-ASA use in pediatric ulcerative colitis (UC.Aim: To evaluate pharmacokinetic and safety profiles of 5-ASA and metabolite acetyl-5-ASA (Ac-5-ASA after once-daily, oral administration of multimatrix mesalamine to children and adolescents with UC.Methods: Participants (5–17 years of age; 18–82 kg, stratified by weight with UC received multimatrix mesalamine 30, 60, or 100 mg/kg/day once daily (to 4,800 mg/day for 7 days. Blood samples were collected pre-dose on days 5 and 6. On days 7 and 8, blood and urine samples were collected and safety was evaluated. 5-ASA and Ac-5-ASA plasma and urine concentrations were analyzed by non-compartmental methods and used to develop a population pharmacokinetic model.Results: Fifty-two subjects (21 [30 mg/kg]; 22 [60 mg/kg]; 9 [100 mg/kg] were randomized. On day 7, systemic exposures of 5-ASA and Ac-5-ASA exhibited a dose-proportional increase between 30 and 60 mg/kg/day cohorts. For 30, 60, and 100 mg/kg/day doses, mean percentages of 5-ASA absorbed were 29.4%, 27.0%, and 22.1%, respectively. Simulated steady-state exposures and variabilities for 5-ASA and Ac-5-ASA (coefficient of variation approximately 50% and 40%–45%, respectively were similar to those observed previously in adults at comparable doses. Treatment-emergent adverse events were

  13. Once-daily glycopyrronium bromide (Seebri Breezhaler(®)) for the treatment of chronic obstructive pulmonary disease (COPD)

    DEFF Research Database (Denmark)

    Ulrik, Charlotte Suppli

    2015-01-01

    glycopyrronium bromide (Seebri Breezhaler®) is a well-tolerated long-acting anti-muscarinic agent (LAMA) with a fast onset of action. In patients with moderate to severe COPD, glycopyrronium bromide has clinically important effects on level of FEV1, use of relief medication, day-time dyspnea scores, and probably...... also on health status. Furthermore, glycopyrronium bromide also has beneficial effects on dynamic hyperinflation and, probably by that, exercise tolerance. Glycopyrronium bromide has been shown to reduce the rate of exacerbations in patients with moderate to severe COPD, although as a secondary outcome...... only. EXPERT OPINION: Once-daily inhaled glycopyrronium bromide has positive impact on important COPD outcomes, comparable to the effects of other marketed LAMAs. Once-daily administration may improve adherence, and glycopyrronium bromide has the potential for a role in the future management of COPD...

  14. Once-daily application of calcipotriene 0.005%-betamethasone dipropionate 0.064% ointment for repigmentation of facial vitiligo.

    Science.gov (United States)

    Newman, Marissa D; Silverberg, Nanette B

    2011-11-01

    Vitiligo vulgaris is an autoimmune pigmentary disorder with no universally efficacious therapeutic options. Separate applications of calcipotriene ointment 0.005% and topical corticosteroid ointments have been successful in the repigmentation of vitiligo. We sought to examine the efficacy of a combination calcipotriene 0.005%-betamethasone dipropionate 0.064% ointment in the repigmentation of vitiligo. An institutional review board-approved retrospective chart review was conducted in 13 pediatric and adult patients with vitiligo treated with calcipotriene 0.005%-betamethasone dipropionate 0.064% ointment once daily for at least 2 months. Two of 3 children had 76% to 100% repigmentation of facial vitiligo with once-daily usage after 2 months. Of the 10 adults (aged 28-55 years), 1 had 100% facial repigmentation in 3 months, 1 had 76% to 99% facial repigmentation in 5 to 9 months, and 2 had 26% to 50% repigmentation in 3 months. Twelve patients developed some facial repigmentation. No patients experienced atrophy, telangiectases, or lesion enlargement during treatment. Combination calcipotriene 0.005%-betamethasone dipropionate 0.064% ointment shows promise as a once-daily vitiligo therapy. Adult and pediatric facial vitiligo patients may see repigmentation as early as 2 months after initiation of therapy. Children may experience a better response, but larger studies are needed.

  15. Five-year follow up of once-daily therapy with emtricitabine, didanosine and efavirenz (Montana ANRS 091 trial).

    Science.gov (United States)

    Molina, Jean-Michel; Journot, Valérie; Furco, André; Palmer, Pierre; De Castro, Nathalie; Raffi, François; Morlat, Philippe; May, Thierry; Rancinan, Corinne; Chêne, Geneviève

    2007-01-01

    Once-daily combination therapy with emtricitabine, didanosine and efavirenz has been highly effective in clinical trials but its long-term efficacy and safety has not been previously reported. This multicentre, single-arm, open-label trial enrolled 40 antiretroviral-naive HIV-1-infected patients who received a once-daily regimen of emtricitabine, didanosine and efavirenz. The objective was to assess the long-term effects of this combination on plasma HIV RNA levels, CD4+ T-cell counts, safety and tolerability. After 5 years, 73% and 68% of patients had plasma HIV RNA levels < 400 and < 50 copies/ml, respectively, in an intent-to-treat, missing-equals-failure analysis. Genotypic resistance on treatment emerged in six patients. There was a significant increase in CD4+ T-cell count of 294 x 10(6) cells/l. Only six patients discontinued study treatment, because of non-severe adverse events. Lipodystrophy was infrequent, and lipid and glucose profiles were favourable with a significant increase in high-density lipoprotein cholesterol. A convenient once-daily regimen of emtricitabine, didanosine and efavirenz provided durable antiretroviral response and was well tolerated through 5 years of therapy.

  16. Once-daily dose regimen of ribavirin is interchangeable with a twice-daily dose regimen: randomized open clinical trial

    Directory of Open Access Journals (Sweden)

    Balk JM

    2015-08-01

    Full Text Available Jiska M Balk,1 Guido RMM Haenen,1 Özgür M Koc,2 Ron Peters,3 Aalt Bast,1 Wim JF van der Vijgh,1 Ger H Koek,4 1Department of Toxicology, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre, 2Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, 3DSM Resolve, Geleen, 4Department of Internal Medicine, Division of Gastroenterology and Hepatology, Maastricht University Medical Centre, Maastricht, the Netherlands Background: The combination of ribavirin (RBV and pegylated interferon (PEG-IFN is effective in the treatment of chronic hepatitis C infection. Reducing the frequency of RBV intake from twice to once a day will improve compliance and opens up the opportunity to combine RBV with new and more specific direct-acting agents in one pill. Therefore, the purpose of this study was to evaluate the pharmacokinetic profile of RBV in a once-daily to twice-daily regimen. The secondary aim was to determine tolerability as well as the severity and differences in side effects of both treatment regimens. Methods: In this randomized open-label crossover study, twelve patients with chronic type 1 hepatitis C infection and weighing more than 75 kg were treated with 180 µg of PEG-IFN weekly and 1,200 mg RBV daily for 24 weeks. The patients received RBV dosed as 1,200 mg once-daily for 12 weeks followed by RBV dosed as 600 mg twice-daily for 12 weeks, or vice versa. In addition to the pharmacokinetic profile, the hematological profile and side effects were recorded. The RBV concentrations in plasma were determined using liquid chromatography-tandem mass spectrometry. Results: Eight of twelve patients completed the study. Neither the time taken for RBV to reach peak plasma concentration nor the AUC0-last (adjusted for difference in dose was significantly different between the two groups (P>0.05. Furthermore, the once-daily regimen did not give more side effects than the twice-daily regimen (P>0

  17. Adaptations of mammary uptake and nutrient use to once-daily milking and feed restriction in dairy cows.

    Science.gov (United States)

    Guinard-Flament, J; Delamaire, E; Lamberton, P; Peyraud, J L

    2007-11-01

    The aim of this study was to gain a clearer understanding of the different levels of regulation involved in the reduction in milk yield in response to once-daily milking and feed restriction. The treatments were designed as a 2 x 2 factorial arrangement of 2 milking frequencies (once- or twice-daily milking) and 2 feeding levels (70 or 98% of requirements determined 1 wk before the trial). The cows were surgically prepared to study the net mammary balance of the nutrients that are precursors of milk components. Mammary efficiency in synthesizing milk components was estimated using a milk output:mammary uptake ratio. No interaction was observed between the effects of milking frequency and feeding level on milk and blood parameters except for milk protein yield, milk fatty acid profile, and nonesterified fatty acids metabolism. Once-daily milking and feed restriction reduced milk yield by 5.1 and 2.9 kg/d and fat-corrected milk yield by 4.2 and 4.1 kg/d, respectively. Both treatments induced a decrease in mammary blood flow. Once-daily milking led to a reduction in the extraction rate of glucose but no changes to the lactose output:glucose uptake ratio. Feed restriction did not change the glucose extraction rate but tended to improve the lactose output:glucose uptake ratio. Under once-daily milking, the slight increase in milk fat content (0.34 percentage units) was linked to a depressed uptake of glucose and acetate but without any variations in the uptake of beta-hydroxybutyrate and total glycerol and in the efficiency of acetate and beta-hydroxybutyrate conversion to short- and medium-chain fatty acids in milk. The decline in milk fat and protein contents (-0.43 and -0.23 percentage units, respectively) under feed restriction was associated with relatively similar reductions in the mammary uptake of all nutrients and with enhanced conversion of the glucose taken up by the mammary gland and used for lactose synthesis. As a result, once-daily milking and feed

  18. Simultaneous population pharmacokinetic modelling of darunavir and ritonavir Once daily in HIV-infected patients: evaluation of lower ritonavir dose

    Directory of Open Access Journals (Sweden)

    L Dickinson

    2012-11-01

    Full Text Available Purpose of study: Once-daily ritonavir-boosted darunavir (DRV/RTV is a preferred antiretroviral regimen for treatment-naïve patients. Population pharmacokinetic modelling of the interaction between DRV and RTV allows evaluation of alternative dosing strategies, particularly lower RTV doses (e.g. 800/50 mg once daily and assessment of factors that may influence DRV/RTV PK. Methods: Data were pooled from 3 DRV/RTV PK studies. Fifty-one HIV-infected patients (7 female stable on DRV/RTV (800/100 mg or 900/100 mg once daily; n=32 and 19, respectively were included. Median age, weight and baseline CD4 cell count were 39 yr (21–63, 74 kg (57–105 and 500 cells/mm3 (227–1129, respectively; 49 had undetectable viral load. Nonlinear mixed effects modelling (Monolix v.4.1.2 was applied simultaneously to DRV and RTV to determine PK parameters, interindividual variability and residual error. Covariates evaluated included: age, weight, sex and study. The model was validated by simulation and visual predictive check. DRV/RTV 800/50 mg once daily was simulated. Summary of results: RTV and DRV were described by a 1 and 2-compartment model, respectively with first-order absorption and lag-time. A maximum effect model, in which RTV inhibited DRV clearance (CL/F, best described the relationship between the two drugs. A RTV concentration of 0.33 mg/L was associated with 50% maximum inhibition of DRV CL/F with the maximum inhibitory effect fixed at 1. The population CL/F of DRV in the absence of RTV was 13.7L/h. Inclusion of weight on RTV CL/F and volume and age on DRV CL/F and study on DRV CL/F, volume and absorption improved the fit. Based on visual predictive check 93% and 91% of observed RTV and DRV concentrations were within the 95% prediction interval, indicative of an adequate model. Of 1000 simulated DRV troughs, 10% and 0% were below the MEC for treatment-experienced (<0.55 mg/L and naïve patients (<0.055 mg/L, respectively. For DRV/RTV 800/50 mg once

  19. Isolated fever induced by mesalamine treatment

    OpenAIRE

    Slim, Rita; Amara, Joseph; Nasnas, Roy; Honein, Khalil; Jaoude, Joseph Bou; Yaghi, Cesar; Daniel, Fady; Sayegh, Raymond

    2013-01-01

    Adverse reactions to mesalamine, a treatment used to induce and maintain remission in inflammatory bowel diseases, particularly ulcerative colitis, have been described in the literature as case reports. This case illustrates an unusual adverse reaction. Our patient developed an isolated fever of unexplained etiology, which was found to be related to mesalamine treatment. A 22-year-old patient diagnosed with ulcerative colitis developed a fever with rigors and anorexia 10 d after starting oral...

  20. Mesalamine for inflammatory bowel disease: recent reappraisals.

    Science.gov (United States)

    Actis, Giovanni C; Pazienza, Paola; Rosina, Floriano

    2008-03-01

    Derived from the historical molecule sulfasalazine, mesalamine has remained one of the mainstays for treatment of inflammatory bowel disease in the last 50 years. Recent advancement in both clinical and basic research has led to reappraise the drug under two crucial aspects. Firstly, there has been a re-evaluation of the chemo-protective effect of mesalamine against sporadic colorectal cancer. Evidence that inflammation plays a strong role in tumor induction from one side, and demonstration that mesalamine can touch on specific molecular steps enhancing apoptosis on the other side have re-shaped the indications of mesalamine for ulcerative colitis. Secondly, the role of thiopurines (azathioprine and 6-MP) in the maintenance of remission of ulcerative colitis has been reiterated by the results of several clinical trials. During attempts at clarifying the reasons why certain patients appear to be resistant to thiopurines, it was interestingly found that mesalamine can interfere thiopurine metabolism, causing an increased blood concentration of the specific immunosuppressive metabolites and a sequential enhancement of drug effectiveness. Mesalamine is therefore being studied as a means to overcome the genetically determined resistance to thiopurines. Such sharpened indications have reiterated attention to correct dosing: the results of controlled trials have shown mesalamine to be fully effective at twice the traditional daily dosage (4.8 grams instead of 2.4). The attendant problems of compliance seem to find solution in the availability of multi-matrix system formulations. This mesalamine story reminds us that in the absence of an etiological target capable to guide research to trace one abrogating molecule, (as it has happened for viral hepatitides for example), treatment of inflammatory bowel disease remains anti-inflammatory in nature and thus multifaceted. Besides justified use of cutting-edge technology to find novel molecules, smart re-evaluation of what is

  1. Pharmacokinetic study of once-daily versus twice-daily abacavir and lamivudine in HIV type-1-infected children aged 3-<36 months

    DEFF Research Database (Denmark)

    NN, NN; Valerius, Niels Henrik

    2010-01-01

    BACKGROUND: Once-daily dosing of abacavir and lamivudine has been approved for adults, but paediatric data are insufficient. We conducted a pharmacokinetic study of once-daily and twice-daily abacavir and lamivudine in children aged 3-... levels after 12 weeks treatment with twice-daily abacavir (8 mg/kg) with or without lamivudine (4 mg/kg) underwent plasma pharmacokinetic sampling. Children then switched to once-daily abacavir (16 mg/kg) with or without lamivudine (8 mg/kg), and sampling was repeated 4 weeks later. The area under......-abacavir (17 for lamivudine). The GMR of AUC(0-24), once-daily versus twice-daily, was 1.07 (90% CI 0.92-1.23) for abacavir and 0.91 (90% CI 0.79-1.06) for lamivudine. C(max) almost doubled on once-daily versus twice...

  2. Clinical impact of laboratory error on therapeutic drug monitoring of once-daily tobramycin in cystic fibrosis: Case series

    Directory of Open Access Journals (Sweden)

    William A Prescott

    2014-01-01

    Full Text Available Once-daily dosing intravenous tobramycin is commonly used to treat cystic fibrosis pulmonary exacerbations. Clinicians often utilize historical therapeutic drug monitoring data to individualize the dose among patients who have been treated with tobramycin previously. This case series involves three patients with cystic fibrosis who had supra-therapeutic tobramycin levels despite use of a once-daily dosing that produced therapeutic drug levels during a previous hospital admission, raising questions about the validity of these levels. Investigation into several potential sources of error led to the discovery of an analyzer error in the laboratory. Once the laboratory’s tobramycin analyzer was recalibrated, the reported levels were comparable to historical levels. This case series emphasizes the clinical importance of critically analyzing reported levels, and specifically, the importance of utilizing past therapeutic drug monitoring data, if available, for all patients treated with intravenous tobramycin. If a patient was therapeutic on a similar dose of tobramycin during a previous admission, a dose adjustment may not be necessary, and clinicians should consider repeating levels while pursuing alternative explanations for the discrepant serum levels.

  3. Randomized efficacy and safety trial of once-daily remogliflozin etabonate for the treatment of type 2 diabetes.

    Science.gov (United States)

    Sykes, A P; Kemp, G L; Dobbins, R; O'Connor-Semmes, R; Almond, S R; Wilkison, W O; Walker, S; Kler, L

    2015-01-01

    The sodium-dependent glucose transporter 2 (SGLT2) inhibitor remogliflozin etabonate (RE) was evaluated in a 12-week, double-blind, randomized, placebo- and active-controlled, parallel-group study. A total of 252 newly diagnosed and drug-naïve people with type 2 diabetes and glycated haemoglobin (HbA1c) concentrations of 7.0-≤9.5% (53-80 mmol/mol) were recruited. Participants were randomized to RE (100, 250, 500 or 1000 mg once daily or 250 mg twice daily), placebo or 30 mg pioglitazone once daily. The primary endpoint was change in HbA1c concentration from baseline. Secondary endpoints included changes in fasting plasma glucose, body weight and lipid profiles, safety and tolerability. We observed a statistically significant trend in the RE dose-response relationship for change from baseline in HbA1c at week 12 (p < 0.047). RE was generally well tolerated and no effects on LDL cholesterol were observed.

  4. Safety and efficacy of bromfenac ophthalmic solution (Bromday) dosed once daily for postoperative ocular inflammation and pain.

    Science.gov (United States)

    Henderson, Bonnie A; Gayton, Johnny L; Chandler, Simon P; Gow, James A; Klier, Sharon M; McNamara, Timothy R

    2011-11-01

    To evaluate the efficacy and ocular safety of bromfenac ophthalmic solution (bromfenac) 0.09% dosed once daily for the treatment of ocular inflammation and pain after cataract surgery with posterior chamber intraocular lens implantation. Randomized, double-masked, vehicle-controlled or active-controlled, multicenter, clinical trials. A total of 872 subjects (872 study eyes: bromfenac in 584, placebo in 288). Four randomized, double-masked, vehicle or active-controlled, clinical trials were conducted at 134 ophthalmology clinics in the United States. Subjects aged ≥ 18 years were randomized to receive either bromfenac 0.09% or placebo dosed once daily beginning 1 day before cataract surgery (day -1), continuing on the day of surgery (day 0), and continuing for an additional postoperative 14 days. Subjects were evaluated for efficacy and safety on days 1, 3, 8, 15, and 22. The primary efficacy end point was cleared ocular inflammation, measured by the summed ocular inflammation score (SOIS; anterior chamber cells and flare) by day 15. The secondary efficacy end point was the number of subjects who were pain-free at day 1. The data from the 4 trials were pooled for analyses. The SOIS and ocular pain. The proportion of subjects who had cleared ocular inflammation by day 15 was significantly higher in the bromfenac 0.09% group than in the placebo group (P < 0.0001). The mean SOIS in the bromfenac 0.09% group was significantly lower than in the placebo group at days 3, 8, 15, and 22 (P < 0.0001). The proportion of subjects who were pain-free at days 1, 3, 8, and 15 was significantly higher in the bromfenac 0.09% group than in the placebo group (P < 0.0001). The incidence of adverse events reported in the bromfenac 0.09% group was significantly lower than in the placebo group (P < 0.0001). On day 15, 84.0% of the bromfenac subjects had ≥ 1-line improvement in visual acuity compared with 66.1% of placebo subjects (P < 0.0001). Bromfenac 0.09% dosed once daily was

  5. Validation and nephrotoxicity of a simplified once-daily aminoglycoside dosing schedule and guidelines for monitoring therapy.

    Science.gov (United States)

    Prins, J M; Weverling, G J; de Blok, K; van Ketel, R J; Speelman, P

    1996-11-01

    There is no established dosing schedule for once-daily aminoglycoside dosing regimens, and accepted guidelines for monitoring therapy are lacking. We derived a simplified schedule from the Hull and Sarubbi (J. H. Hull and F. A. Sarubbi, Ann. Intern. Med. 85:183-189, 1976) nomogram, for which efficacy and safety in a once-daily dosing regimen were previously demonstrated, and prospectively followed serum aminoglycoside levels in patients. The standard treatment was gentamicin or tobramycin at 4 mg/kg of body weight given intravenously once daily. When the renal function was decreased, the daily dose was reduced, as follows: for an estimated creatinine clearance of between 50 and 80 ml/min, the daily dose was 3.25 mg/kg, for an estimated creatinine clearance of between 30 and 50 ml/min, the daily dose was 2.5 mg/kg, and for an estimated creatinine clearance of below 30 ml/min, the daily dose was 2 mg/kg. A total of 221 patients were studied (184 received gentamicin and 37 received tobramycin). First trough levels above 2 mg/liter were recorded in 11% of the patients, and they all had a baseline creatinine clearance below 50 ml/min, or a substantial decrease in clearance between enrollment and the day that the trough level was obtained. A peak level below 6 mg/liter was recorded in 6% of the patients, and half of them received the lowest daily dose. Twenty-five of the 179 evaluable patients (14%; 95% confidence interval, 9 to 19%) fulfilled the criteria for nephrotoxicity. In a multiple regression analysis, the duration of treatment and the use of other nephrotoxic antibiotics or high-dose furosemide, but not trough levels, were significant risk factors. Since the meaning of low peak levels is unclear and since most studies with multiple daily regimens confirm the lack of an association between trough levels and toxicity, we believe that monitoring of serum drug levels can be restricted to monitoring of trough levels in patients with a creatinine clearance below 50 ml

  6. Efficacy and tolerability of once-daily barnidipine in the clinical management of patients with mild to moderate essential hypertension.

    Science.gov (United States)

    Spieker, C

    1998-01-01

    Four multicentre trials have investigated the efficacy and tolerability of treatment with once-daily, modified-release capsules of barnidipine, a long-acting dihydropyridine calcium antagonist, in patients with mild to moderate essential hypertension. In two of these trials, the clinical profile of barnidipine was compared with those of amlodipine and nitrendipine, which belong to the same class of drug as barnidipine, in a randomized, double-blind, parallel-group manner. In one study, 37 patients received amlodipine and 79 patients received barnidipine. In a second study, 46 patients received nitrendipine and 96 received barnidipine. In each trial, a 4-week placebo run-in phase was followed by a 12-week comparative phase. Changes in sitting and standing diastolic and systolic blood pressures were assessed, and adverse events were recorded. Both studies demonstrated that the antihypertensive efficacy of barnidipine was equivalent to each comparator agent, but barnidipine tended to produce fewer class I adverse reactions. The long-term efficacy and safety of barnidipine were demonstrated in an open-label study. In total, 106 patients were followed for the first year of the study, during which time they received barnidipine at a dose titrated to achieve a sitting diastolic blood pressure of less than 90 mm Hg; if necessary, another antihypertensive agent was added to achieve normalization of blood pressure. Seventy-nine of these patients, most of whom were maintained on barnidipine monotherapy, were followed for a second year, and 32 patients, all of whom received barnidipine monotherapy throughout the study period, were followed for a third year. Blood pressure normalization after 1 year of follow-up was achieved in 91% of patients, and was maintained for the second and third years in 91% and 81% of patients, respectively. The incidence of adverse events, possibly or probably attributable to barnidipine, was 22%, 14% and 3%, respectively, during each successive year

  7. Once-daily NVA237 improves exercise tolerance from the first dose in patients with COPD: the GLOW3 trial

    Directory of Open Access Journals (Sweden)

    Beeh KM

    2012-07-01

    Full Text Available Kai M Beeh,1 Dave Singh,2 Lilla Di Scala,3 Anton Drollmann31insaf Respiratory Research Institute, Wiesbaden, Germany; 2University Of Manchester, Medicines Evaluation Unit, University Hospital of South Manchester, Manchester, UK; 3Novartis Pharma AG, Basel, SwitzerlandIntroduction: Exercise limitation, dynamic hyperinflation, and exertional dyspnea are key features of symptomatic chronic obstructive pulmonary disease (COPD. We assessed the effects of glycopyrronium bromide (NVA237, a once-daily, long-acting muscarinic antagonist, on exercise tolerance in patients with moderate to severe COPD.Methods: Patients were randomized to a cross-over design of once-daily NVA237 50 µg or placebo for 3 weeks, with a 14-day washout. Exercise endurance, inspiratory capacity (IC during exercise, IC and expiratory volumes from spirometry, plethysmographic lung volumes, leg discomfort and dyspnea under exercise (Borg scales, and transition dyspnea index were measured on Days 1 and 21 of treatment. The primary endpoint was endurance time during a submaximal constant-load cycle ergometry test on Day 21.Results: A total of 108 patients were randomized to different treatment groups (mean age, 60.5 years; mean post-bronchodilator, forced expiratory volume in 1 second [FEV1] 57.1% predicted. Ninety-five patients completed the study. On Day 21, a 21% difference in endurance time was observed between patients treated with NVA237 and those treated with placebo (P < 0.001; the effect was also significant from Day 1, with an increase of 10%. Dynamic IC at exercise isotime and trough FEV1 showed significant and clinically relevant improvements from Day 1 of treatment that were maintained throughout the study. This was accompanied by inverse decreases in residual volume and functional residual capacity. NVA237 was superior to placebo (P < 0.05 in decreasing leg discomfort (Borg CR10 scale on Day 21 and exertional dyspnea on Days 1 and 21 (transition dyspnea index and Borg CR

  8. Mesalamine treatment mimicking relapse in a child with ulcerative colitis

    Institute of Scientific and Technical Information of China (English)

    Iva Hojsak; Ana M Pavić; Sanja Kolaček

    2014-01-01

    Background: There are reports on mesalamine-induced bloody diarrhea mimicking ulcerative colitis (UC) relapse, mostly in adults. Methods: Herein we present a case of a child with UC who developed relapse of hemorrhagic colitis related to mesalamine. Results: A 10-year-old girl developed severe symptoms mimicking UC relapse 3 weeks after introduction of mesalamine therapy. After mesalamine was withdrawn, her symptoms improved, but deteriorated again during the challenge of mesalamine despite concomitant use of corticosteroids. Conclusion: This is the fi rst case report on such a young child during the concomitant use of corticosteroids.

  9. Once-daily atomoxetine for treating pediatric attention-deficit/hyperactivity disorder: comparison of morning and evening dosing.

    Science.gov (United States)

    Block, Stan L; Kelsey, Douglas; Coury, Daniel; Lewis, Donald; Quintana, Humberto; Sutton, Virginia; Schuh, Kory; Allen, Albert J; Sumner, Calvin

    2009-09-01

    In this 3-arm, randomized, double-blind trial, once-daily morning-dosed atomoxetine, evening-dosed atomoxetine, and placebo were compared for treating pediatric attention-deficit/hyperactivity disorder (ADHD). Patients received morning atomoxetine/evening placebo (n = 102), morning placebo/evening atomoxetine (n = 93), or morning placebo/evening placebo (n = 93) for about 6 weeks. Core symptom efficacy was measured at weeks 0, 1, 3, and 6. Parent assessments of the child's home behaviors in the evening and early morning were collected daily during the first 2 weeks of treatment. Morning-dosed and evening-dosed atomoxetine significantly decreased core ADHD symptoms relative to placebo and produced symptom improvements that were measured up to 24 hours later. Morning dosing was superior to evening dosing on some efficacy measures. Evening dosing showed greater tolerability with significantly more patients receiving morning atomoxetine reporting at least 1 adverse event than those receiving evening atomoxetine.

  10. Effect of once-daily generic ciclesonide on exhaled nitric oxide in atopic children with persistent asthma.

    Science.gov (United States)

    Mallol, J; Aguirre, V; Gallardo, A; Cortez, E; Sánchez, C; Riquelme, C; Córdova, P; Martínez, M; Galindo, A

    2016-01-01

    Ciclesonide (CIC) is an effective inhaled corticosteroid for treating asthmatic children. However, its effect on airway inflammation assessed by the fraction of exhaled nitric oxide (FENO) in children with persistent asthma is virtually unknown. We aimed to assess the effect of once-daily generic CIC, 80 or 160 μg, on FENO, lung function, asthma control and bronchial hyperresponsiveness, in atopic children with persistent asthma. This was a 12-week, randomised, double-blind, parallel-group study. Sixty children with mild-to-moderate persistent asthma were recruited. Changes in FENO, asthma control score, lung function (FEV1) and bronchial hyperresponsiveness to methacholine (BHR) were used to assess the effects of both CIC doses. Non-normally distributed variables were log-transformed to approximate normality, and parametric tests were used for comparisons within and between groups at baseline and after 12 weeks of treatment. In the CIC 80 μg group, FENO decreased from 45.0 ppb (95% CI 37.8-53.7) to 32.7 ppb (95% CI 21.0-47.3) at the end of study (P=0.021), whereas in the CIC 160 μg group, FENO decreased from 47.3 ppb (95% CI 40.4-55.3) to 30.5 ppb (95% CI 24.1-38.7) (Pasthma control with both CIC doses but there was no significant change in BHR or FEV1 in either group. Once-daily generic ciclesonide (80 μg or 160 μg), for 12 weeks, is effective to improve airway inflammation and asthma control in atopic children with persistent asthma. Copyright © 2014 SEICAP. Published by Elsevier Espana. All rights reserved.

  11. Indacaterol once-daily provides superior efficacy to salmeterol twice-daily in COPD: a 12-week study.

    Science.gov (United States)

    Korn, Stephanie; Kerwin, Edward; Atis, Sibel; Amos, Carolynn; Owen, Roger; Lassen, Cheryl

    2011-05-01

    Indacaterol is a novel, inhaled once-daily ultra-long-acting β(2)-agonist for the treatment of COPD. This 12-week randomised, parallel-group study compared the efficacy of indacaterol 150 μg once-daily to salmeterol 50 μg twice-daily in patients with moderate-to-severe COPD. Assessments included FEV(1) standardised area under curve (AUC) from 5 min to 11 h 45 min at Week 12 (primary endpoint), 24-h trough FEV(1) (mean of 23 h 10 min and 23 h 45 min post-dose) at Week 12 (key secondary endpoint), FEV(1) and FVC measured over 24-h, transition dyspnoea index (TDI) and rescue medication use. Of 1123 patients randomised 92.1% completed. Mean ± SD age was 62.8±8.78 years, post-bronchodilator FEV(1) 51.8±12.32% predicted, FEV(1)/FVC 50.6±9.54%. At Week 12, FEV(1) AUC(5 min-11 h 45 min) for indacaterol was statistically superior (pIndacaterol also showed statistical superiority over salmeterol in terms of FEV(1) and FVC measured over 24-h at Week 12. For TDI at Week 12, the mean total score was statistically superior for indacaterol versus salmeterol (difference 0.63 [0.30, 0.97], pindacaterol used fewer puffs/day (difference -0.18 [-0.36, 0.00] puffs/day, pindacaterol provided statistically superior bronchodilation with an improvement in breathlessness and rescue use compared with twice-daily salmeterol. ClinicalTrials.gov NCT00821093. Copyright © 2011 Elsevier Ltd. All rights reserved.

  12. The efficacy and safety of high-dose arbekacin sulfate therapy (once-daily treatment) in patients with MRSA infection.

    Science.gov (United States)

    Yamamoto, Yoshihiro; Izumikawa, Koichi; Hashiguchi, Koji; Fukuda, Yuichi; Kobayashi, Tsutomu; Kondo, Akira; Inoue, Yuichi; Morinaga, Yoshitomo; Nakamura, Shigeki; Imamura, Yoshifumi; Miyazaki, Taiga; Kakeya, Hiroshi; Yanagihara, Katsunori; Kohno, Shigeru

    2012-04-01

    The efficacy and safety of once-daily high-dose arbekacin sulfate therapy for methicillin-resistant Staphylococcus aureus (MRSA) infection were evaluated, with analysis of their relationship to blood drug levels. The study was conducted in patients with pneumonia or sepsis, the cause of which was suspected to be MRSA, who were admitted to the Nagasaki University Hospital or its affiliated hospitals between January 2009 and December 2010. The initial drug dose was set at a level expected to yield the goal peak of 20 μg/ml and a trough level of less than 2 μg/ml, using the Habekacin Therapeutic Drug Monitoring analysis software. Thirteen patients were enrolled: 10 patients had pneumonia and 3 patients had sepsis. Patient mean age was 72.0 years; mean initial drug dose was 269.2 mg. Clinical efficacy at completion of treatment and bacterial eradication-reduction were achieved in 66.7% (6/9) and 62.5% (5/8) of patients, respectively. Incidence of adverse reactions was 38.5% (5/13). In analysis of efficacy in relationship to serum drug levels, the peak drug level was 22.7 ± 5.50 μg/ml, on average, and 15 μg/ml or higher in all 6 responders. Also, in patients with renal dysfunction, it seemed to be essential to ensure a certain peak drug level and to control the trough level appropriately. Although the number of patients was limited, once-daily high-dose arbekacin sulfate therapy may be highly effective, without posing any major safety problems. Further larger-scale studies are needed.

  13. Efficacy, safety, and tolerability of overnight switching from immediate- to once daily extended-release pramipexole in early Parkinson's disease.

    Science.gov (United States)

    Rascol, Olivier; Barone, Paolo; Hauser, Robert A; Mizuno, Yoshikuni; Poewe, Werner; Schapira, Anthony H V; Salin, Laurence; Sohr, Mandy; Debieuvre, Catherine

    2010-10-30

    The aim of this article is to test the feasibility, in early Parkinson's disease (PD), of an overnight switch from immediate-release (IR) pramipexole to a new once-daily extended-release (ER) formulation. Nonfluctuating patients on pramipexole IR three-times daily, alone or with levodopa, for early PD were randomly switched overnight to double-blind IR three-times daily (N = 52) or ER once-daily (N = 104) at initially unchanged daily dosage. Successful switching (defined as no worsening >15% of baseline UPDRS II+III score and no drug-related adverse event withdrawal) was assessed at 9 weeks, after optional dosage adjustments (primary endpoint), and at 4 weeks, before adjustment. Other secondary endpoints included adjusted mean changes from baseline in UPDRS scores and proportion of responders based on Clinical or Patient Global Impression (CGI/PGI). Absolute difference between percentage of successful switch to ER versus IR was tested for ER noninferiority, defined as a 95% confidence-interval lower bound not exceeding -15%. At 9 weeks, 84.5% of the ER group had been successfully switched, versus 94.2% for IR. Noninferiority was not demonstrated, with a difference of -9.76% (95% CI: [-18.81%, +1.66%]). At 4 weeks, 81.6% of the ER group had been successfully switched, versus 92.3% for IR, a difference of -10.75% (95% CI: [-20.51%, +1.48%]). UPDRS changes and CGI/PGI analyses showed no differences between the groups. Both formulations were safe and well tolerated. Pramipexole ER was not equivalent to IR, but the difference was marginal. The fact that >80% of the patients successfully switched overnight at unchanged dosage shows that this practice was feasible in most patients.

  14. Pharmacokinetics of tacrolimus converted from twice-daily formulation to once-daily formulation in Chinese stable liver transplant recipients

    Institute of Scientific and Technical Information of China (English)

    Yi-fan ZHANG; Xiao-yan CHEN; Xiao-jian DAI; Xi-sheng LENG; Da-fang ZHONG

    2011-01-01

    Aim:To evaluate the pharmacokinetics of tacrolimus in Chinese stable liver transplant recipients converted from immediate release (IR) tacrolimus-based immunosuppression to modified release (MR) tacrolimus-based immunosuppression.Methods:Open-label,multi-center study with a one-way conversion design was conducted.Eighty-three stable liver recipients (6-24 months post-transplant) with normal renal and stable hepatic function were converted from IR tacrolimus twice-daily treatment to MR tacrolimus once-daily treatment on a 1:1 (mg:mg) total daily dose basis.Twenty-four hour pharmacokinetic studies were carried out on d 0 (pre-conversion),d 1,and d 84 (post-conversion).Results:The area under the blood concentration-time curve of MR tacrolimus from 0 to 24 h (AUC0-24) on d 1 was comparable to that of IR tacrolimus on d 0,with a 90% confidence interval (CI) for MR/IR tacrolimus of 92%-97%.The AUC0-24 value for MR tacrolimus on d 84 with the daily dose increased by 14% was approximately 17% lower than that for IR tacrolimus.The 90% CI was 77%-90%,outside the bioequivalence range of 80%-125%.There was a good correlation between AUC0-24 and concentration at 24 h (C24) for IR tacrolimus (d 0,r=0.930) and MR tacrolimus (d 1,r=0.936; d 84,r=0.903).Conclusion:The exposure to tacrolimus when administered MR tacrolimus once daily is not equivalent to that for IR tacrolimus twice daily after an 84-day conversion in Chinese stable liver transplant recipients.The dose should be adjusted on the basis of trough levels.The therapeutic drug monitoring for patients treated with IR tacrolimus is considered to be applicable to MR tacrolimus.

  15. Mesalamine

    Science.gov (United States)

    ... experiencing a reaction to the medication or a flare (episode of symptoms) of your disease. Call your ... stiffness back pain nausea vomiting heartburn burping constipation gas dry mouth itching dizziness sweating acne slight hair ...

  16. Efficacy, Safety and Pharmacokinetics of Once-Daily Saquinavir Soft-Gelatin Capsule/Ritonavir in Antiretroviral-Naive, HIV-Infected Patients

    OpenAIRE

    Julio, Montaner SG; Schutz, Malte; Schwartz, Robert; Jayaweera, Dushyantha T; Burnside, Alfred F; Walmsley, Sharon; Saag, Michael S.

    2006-01-01

    Context Once-daily HIV treatment regimens are being used in clinical practice with the objective of improving patient acceptance and adherence. Objective To evaluate the efficacy and safety of saquinavir-soft-gelatin capsule (SGC)/ritonavir combination (1600 mg/100 mg) vs efavirenz (600 mg) both once daily and combined with 2 nucleoside analogs twice daily. Setting Twenty-six centers in the United States, Canada, and Puerto Rico. Patients A total of 171 antiretroviral naive HIV-infected indiv...

  17. Efficacy, Safety and Pharmacokinetics of Once-Daily Saquinavir Soft-Gelatin Capsule/Ritonavir in Antiretroviral-Naive, HIV-Infected Patients

    OpenAIRE

    Julio SG Montaner; Schutz Malte; Schwartz Robert; Jayaweera Dushyantha T; Burnside Alfred F; Walmsley Sharon; Saag Michael S

    2006-01-01

    Abstract Context Once-daily HIV treatment regimens are being used in clinical practice with the objective of improving patient acceptance and adherence. Objective To evaluate the efficacy and safety of saquinavir-soft-gelatin capsule (SGC)/ritonavir combination (1600 mg/100 mg) vs efavirenz (600 mg) both once daily and combined with 2 nucleoside analogs twice daily. Setting Twenty-six centers in the United States, Canada, and Puerto Rico. Patients A total of 171 antiretroviral naive HIV-infec...

  18. Mesalamine-induced myopericarditis: a case report

    Directory of Open Access Journals (Sweden)

    Sónia Bernardo

    Full Text Available Myopericarditis has occasionally been reported as a side effect of mesalamine in patients with inflammatory bowel disease. We present a 20-year-old woman with ulcerative colitis admitted with chest pain. After thorough investigation she was diagnosed with myopericarditis potentially related to mesalamine. There was complete clinical and laboratorial recovery following drug withdrawal. Although uncommon, the possibility of myopericarditis should be considered in patients with inflammatory bowel disease presenting with cardiac complaints. Early recognition can avoid potential life-threatening complications.

  19. Accelerated partial breast irradiation using once-daily fractionation: analysis of 312 cases with four years median follow-up

    Directory of Open Access Journals (Sweden)

    Shaikh Arif Y

    2012-02-01

    Full Text Available Abstract Background There are limited data on accelerated partial breast irradiation (APBI using external beam techniques. Moreover, there are recent reports of increased fibrosis and unacceptable cosmesis with APBI using external beam with BID fractionation. We adopted a once daily regimen of APBI with fractionation similar to that shown to be effective in a Canadian randomized trial of whole breast irradiation. It is unclear whether patients with DCIS or invasive lobular carcinoma (ILC are suitable for APBI. Methods The retrospective cohort included 310 patients with 312 tumors of T1-T2N0-N1micM0 invasive ductal carcinoma (IDC, ILC, or Tis (DCIS treated with APBI via external beam. Most patients were treated using IMRT with 16 daily fractions of 270 cGy to a dose of 4320 cGy. The target volume included the lumpectomy cavity plus 1.0 cm to account for microscopic disease and an additional 0.5 to 1.0 cm for setup uncertainty and breathing motion. Ipsilateral breast failure (IBF was pathologically confirmed as a local failure (LF or an elsewhere failure (EF. Results Median follow-up was 49 months. Among the 312 cases, 213 were IDC, 31 ILC, and 68 DCIS. Median tumor size was 1.0 cm. There were 9 IBFs (2.9% including 5 LFs and 4 EFs. The IBF rates among patients with IDC, ILC, and DCIS were 2.4%, 3.2%, and 4.4%, respectively, with no significant difference between histologies. When patients were analyzed by the ASTRO APBI consensus statement risk groups, 32% of treated cases were considered suitable, 50% cautionary, and 18% unsuitable. The IBF rates among suitable, cautionary, and unsuitable patients were 4.0%, 2.6%, and 1.8%, respectively, with no significant difference between risk groups. Acute skin reactions were rare and long-term cosmetic outcome was very good to excellent. Conclusions External beam APBI with once daily fractionation has a low rate of IBF consistent with other published APBI studies. The ASTRO risk stratification did not

  20. Bronchodilator efficacy and safety of indacaterol 150 µg once daily in patients with COPD: an analysis of pooled data

    Directory of Open Access Journals (Sweden)

    Bleecker ER

    2011-08-01

    Full Text Available Eugene R Bleecker1, Thomas Siler2, Roger Owen3, Benjamin Kramer41Center for Genomics and Personalized Medicine Research and Translational Medicine Institute, Wake Forest University Health Sciences, Winston-Salem, NC, USA; 2Midwest Chest Consultants, Saint Charles, MO, USA; 3Novartis Horsham Research Centre, Horsham, West Sussex, UK; 4Respiratory Development, Novartis Pharmaceuticals Corporation, East Hanover, NJ, USABackground: Indacaterol is an inhaled, once-daily long-acting β2-agonist bronchodilator for regular use in patients with chronic obstructive pulmonary disease (COPD. As indacaterol is the first once-daily β2-agonist to be developed, it is relevant to evaluate its bronchodilator efficacy, safety, and tolerability.Methods: Data were pooled from three randomized, double-blind, clinical studies in patients with moderate-to-severe COPD treated with indacaterol 150 µg qd (n = 627 or placebo (n = 1021. Bronchodilator efficacy was assessed as trough (24-hour post-dose forced expiratory volume in 1 second (FEV1 after 12 weeks (primary endpoint in individual studies and FEV1 measured serially post-dose. Rescue use of albuterol was monitored.Results: At week 12, indacaterol increased trough FEV1 by 160 mL compared with placebo (P < 0.001, exceeding the 120 mL level prespecified as clinically important. FEV1 during the first 12-hour post-dose at week 12 averaged 210 mL higher with indacaterol than with placebo (P < 0.001. Patients receiving indacaterol recorded 53% of days without use of rescue albuterol, compared with 38% of days in the placebo group (P < 0.001. Adverse events (mostly mild or moderate were reported for 52% and 46% of patients receiving indacaterol and placebo, respectively, and serious adverse events for 4% and 5%. Worsening of COPD was the most frequent adverse event (10% indacaterol; 15% placebo. Indacaterol had little effect on pulse or blood pressure or measures of systemic β2-adrenoceptor activity (blood glucose, serum

  1. Profile of once-daily darunavir/cobicistat fixed-dose combination for the treatment of HIV/AIDS

    Science.gov (United States)

    Navarro, Jordi; Curran, Adrian

    2016-01-01

    Efficacy is the main objective of antiretroviral treatment and adherence is one of the cornerstones to achieve it. For this reason, treatment simplification is of key importance with regard to antiretroviral regimens. Rezolsta® (darunavir/cobicistat) is the first fixed-dose combination containing a protease inhibitor approved for HIV treatment. This coformulation includes darunavir, a protease inhibitor that has shown its efficacy and safety in naïve and treatment-experienced patients, and cobicistat, the new pharmacokinetic enhancer that is expected to replace ritonavir. Bioequivalence between ritonavir and cobicistat as darunavir boosters has been shown in studies involving healthy volunteers. Furthermore, efficacy and safety of darunavir/cobicistat observed in phase III studies, including naïve and pretreated patients without darunavir-associated resistance mutations, are comparable to historical data of darunavir/ritonavir 800/100 mg once-daily formulation. Adverse events with darunavir/cobicistat are scarce and mild, and basically include skin reactions and gastrointestinal disturbances. Although small increases in plasma creatinine are expected in patients receiving cobicistat due to the inhibition of creatinine transporters in kidney tubules, actual glomerular filtrate rate remains unaltered. Cobicistat does not have an inducer effect on metabolic pathways and shows much more selective inhibition than ritonavir. Therefore, isoenzyms different from CYP3A4 are supposed to be less affected by cobicistat, and thus fewer drug–drug interactions are expected. PMID:27843352

  2. Once-daily rupatadine improves the symptoms of chronic idiopathic urticaria: a randomised, double-blind, placebo-controlled study.

    Science.gov (United States)

    Dubertret, Louis; Zalupca, Lavinia; Cristodoulo, Tania; Benea, Vasile; Medina, Iris; Fantin, Sara; Lahfa, Morad; Pérez, Iñaki; Izquierdo, Iñaki; Arnaiz, Eva

    2007-01-01

    This randomised, double-blind, placebo-controlled, parallel-group, international, dose-ranging study investigated the effect of treatment with rupatadine 5, 10 and 20 mg once daily for 4 weeks on symptoms and interference with daily activities and sleep in 12-65 years-old patients with moderate-to-severe chronic idiopathic urticaria (CIU). Rupatadine 10 and 20 mg significantly reduced pruritus severity by 62.05% and 71.87% respectively, from baseline, over a period of 4 weeks compared to reduction with placebo by 46.59% (p < 0.05). Linear trends were noted for reductions in mean number of wheals and interference with daily activities and sleep with rupatadine 10 and 20 mg over the 4-week treatment period. The two most frequently reported AEs were somnolence (2.90% for placebo, 4.29% for 5 mg-, 5.41% for 10 mg- and 21.43% for 20 mg-rupatadine-treated group) and headache (4.35% for placebo, 2.86% for 5 mg-, 4.05% for 10 mg- and 4.29% for 20 mg-rupatadine-treated group). These findings suggest that rupatadine 10 and 20 mg is a fast-acting, efficacious and safe treatment for the management of patients with moderate-to-severe CIU. Rupatadine decreased pruritus severity, in a dose- and time-dependent manner.

  3. Comparison of health care resource utilization and costs among patients with GERD on once-daily or twice-daily proton pump inhibitor therapy

    Directory of Open Access Journals (Sweden)

    Mody R

    2013-04-01

    Full Text Available Reema Mody,1 Debra Eisenberg,2 Likun Hou,2 Siddhesh Kamat,2 Joseph Singer,2 Lauren B Gerson3 1Takeda Pharmaceuticals International Inc, Deerfield, IL, 2HealthCore Inc, Wilmington, DE, 3Stanford University School of Medicine, Stanford, CA, USA Background: The purpose of this study was to assess differences in health care resource utilization and costs associated with once-daily and twice-daily proton pump inhibitor (PPI therapy. Most patients with gastroesophageal reflux disease (GERD achieve symptom control on once-daily PPI therapy, but approximately 20%–30% require twice-daily dosing. Methods: Patients were ≥18 years of age with at least one medical claim for GERD and at least two PPI claims from HealthCore's Integrated Research Database (HIRDSM during 2004–2009. Patients were continuously eligible for 12 months before and after the index date (date of first PPI claim. Based on PPI dosing throughout the post-index period (quantity of medication dispensed/number of days supply, patients were classified as once-daily (dose ≤ 1.5 pills per day or twice-daily (≥1.5 PPI users. Results: The study cohort included 248,386 patients with GERD (mean age 52.8 ± 13.93 years, 56% females of whom 90% were once-daily and 10% were twice-daily PPI users. The Deyo-Charlson Comorbidity Index for once-daily and twice-daily PPI users was 0.70 ± 1.37 and 0.89 ± 1.54, respectively (P < 0.05. More once-daily patients had claims for Barrett's esophagus (5% versus 2%, P < 0.0001 than twice-daily patients. Post-index, higher proportions of twice-daily patients had at least one GERD-related inpatient visit (7% versus 5%, outpatient visit (60% versus 49%, and office visit (48% versus 38% versus once-daily patients (P < 0.0001. Mean total GERD-related health care costs were $2065 ± $6636 versus $3749 ± $11,081 for once-daily and twice-daily PPI users, respectively (P < 0.0001. Conclusion: Patients receiving twice-daily PPI therapy were likely to have more

  4. Twice-daily versus once-daily antiretroviral therapy and coformulation strategies in HIV-infected adults: benefits, risks, or burden?

    Science.gov (United States)

    Nachega, Jean B; Rosenkranz, Bernd; Pham, Paul A

    2011-01-01

    The recent development of once-daily antiretroviral agents and fixed-dose combination formulations has been an important development in antiretroviral regimen simplification. Recent studies indicate that once-daily antiretroviral regimens improve adherence, especially in antiretroviral-naïve patients and in difficult-to-treat populations, such as the homeless or marginally housed. However, there are potential risks with the higher peak and lower trough plasma drug concentrations that may result from certain once-daily formulations. Due to the multifactorial and complex nature of adherence behavior, clinicians’ efforts to improve patient adherence should not be limited to prescribing once-daily regimens, but should also consider social support, side effect management, and adherence support tools, such as pillbox organizers and other targeted interventions. Additional research will clarify the benefits of once-daily and fixed-dose combination regimens on clinical and virologic outcomes. Comprehensive cost-benefit analysis of regimen simplification could help facilitate evidence-based decisions regarding antiretroviral regimen choices. PMID:22259241

  5. Ulcerative colitis flair induced by mesalamine suppositories hypersensitivity.

    Science.gov (United States)

    Ding, Hao; Liu, Xiao-Chang; Mei, Qiao; Xu, Jian-Ming; Hu, Xiang-Yang; Hu, Jing

    2014-04-07

    Mesalamine suppositories have been used widely for the treatment of distal ulcerative colitis and considered to be safer than systemic administration for its limited systemic absorption. However, previous studies have shown that mesalamine suppository occasionally causes severe hypersensitivity reactions including fever, rashes, colitis exacerbation and acute eosinophilic pneumonia. Here we present a 25-year-old woman with ulcerative colitis with bloody diarrhea accompanied by abdominal pain and fever which were aggravated after introduction of mesalamine suppositories. In light of symptom exacerbation of ulcerative colitis, increased inflammatory injury of colon mucosa shown by colonoscopy and elevated peripheral eosinophil count after mesalamine suppositories administration, and the Naranjo algorithm score of 10, the possibility of hypersensitivity reaction to mesalamine suppositories should be considered, warning us to be aware of this potential reaction after administration of mesalamine formulations even if it is the suppositories.

  6. Cost-utility analysis of indacaterol in Germany: a once-daily maintenance bronchodilator for patients with COPD.

    Science.gov (United States)

    Price, David; Gray, Alastair; Gale, Rupert; Asukai, Yumi; Mungapen, Laura; Lloyd, Adam; Peters, Lars; Neidhardt, Katja; Gantner, Tobias

    2011-11-01

    Indacaterol is a novel inhaled once-daily long-acting beta(2)-agonist (LABA) for the maintenance treatment of COPD that has been compared to existing inhaled monotherapies on a number of symptomatic endpoints in clinical studies. With constrained healthcare budgets, the objective of this analysis was to evaluate the cost-effectiveness of indacaterol 150 μg, the approved starting dose for maintenance therapy, from a German heath service perspective against the most widely used bronchodilator tiotropium, and the twice-daily LABA, salmeterol. A Markov model was developed with the following main health states: Mild, Moderate, Severe, and Very Severe COPD, based on pre-bronchodilator FEV(1) measures reported in the indacaterol clinical trials, and death. Each disease severity health state had two associated health states for severe or non-severe exacerbation. The model considered patients with moderate to severe COPD, with a mean age of 64 years. The base case time horizon was three years, with discounting set at 3% for costs and benefits. Selected clinical inputs and health state utilities were derived from indacaterol clinical trials, while costs were based on publicly available drug prices and tariffs or published sources. Inputs describing disease progression were based on published data on the rate of FEV(1) decline. Point-estimates show that indacaterol 150 μg is dominant (lower total costs and better outcomes) against tiotropium and salmeterol. An alternative analysis comparing indacaterol 300 μg (maximum dose) against tiotropium, showed an incremental cost-effectiveness ratio (ICER) of approximately €28,300 per QALY. Indacaterol is cost-effective compared to tiotropium and salmeterol. Copyright © 2011 Elsevier Ltd. All rights reserved.

  7. Automated telecommunication-based reminders and adherence with once-daily glaucoma medication dosing: the automated dosing reminder study.

    Science.gov (United States)

    Boland, Michael V; Chang, Dolly S; Frazier, Travis; Plyler, Ryan; Jefferys, Joan L; Friedman, David S

    2014-07-01

    Topical glaucoma medications lower intraocular pressure and alter the course of the disease. Because adherence with glaucoma medications is a known problem, interventions are needed to help those patients who do not take their medications as prescribed. To assess the ability of an automated telecommunication-based intervention to improve adherence with glaucoma medications. We performed a prospective cohort study of medication adherence, followed by a randomized intervention for those found to be nonadherent, of individuals recruited from a university-based glaucoma subspecialty clinic. A total of 491 participants were enrolled in the initial assessment of adherence. Of those, 70 were nonadherent with their medications after 3 months of electronic monitoring and randomized to intervention and control groups. A personal health record was used to store the list of patient medications and reminder preferences. On the basis of those data, participants randomized to the intervention received daily messages, either text or voice, reminding them to take their medication. Participants randomized to the control group received usual care. Difference in adherence before and after initiation of the intervention. Using an intent-to-treat analysis, we found that the median adherence rate in the 38 participants randomized to the intervention increased from 53% to 64% (P telecommunication-based reminders linked to data in a personal health record improved adherence with once-daily glaucoma medications. This is an effective method to improve adherence that could realistically be implemented in ophthalmology practices with a minimum amount of effort on the part of the practice or the patient.

  8. Effects of once-daily extended release quetiapine fumarate on patient-reported outcomes in patients with generalized anxiety disorder

    Directory of Open Access Journals (Sweden)

    Endicott J

    2012-07-01

    Full Text Available Jean Endicott,1 Henrik Svedsäter,2 Julie C Locklear21Department of Psychiatry, Columbia University, New York, NY; 2AstraZeneca Pharmaceuticals, Wilmington, DE, USABackground: We evaluated the effects of once-daily extended-release quetiapine fumarate (quetiapine XR on patient-reported outcomes in generalized anxiety disorder (GAD.Methods: This is a report of a pooled analysis from three acute 8-week, randomized, placebo-controlled, fixed-dose (50, 150, 300 mg/day studies and a 52-week maintenance flexible dose (50–300 mg/day study of quetiapine XR monotherapy in patients with GAD. Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF percent maximum total scores (items 1–14, item 15 ("satisfaction with medication", item 16 ("overall life satisfaction", and Pittsburgh Sleep Quality Index (PSQI global scores are reported. Sheehan Disability Scale (SDS total scores were also assessed (maintenance study only.Results: The acute studies showed significant improvements at week 8 in Q-LES-Q-SF percent maximum total score with quetiapine XR 150 mg/day (P < 0.001 and item 16 with quetiapine XR 50 (P < 0.05 and 150 mg/day (P < 0.001 versus placebo; PSQI global scores significantly improved with quetiapine XR 50, 150, and 300 mg/day versus placebo (P < 0.001. The maintenance study showed significant benefits versus placebo with quetiapine XR 50–300 mg/day in Q-LES-Q-SF percent total score, item 15 and item 16 scores, PSQI global score, and SDS total score.Conclusion: Quetiapine XR 150 mg/day (acute studies and 50–300 mg/day (maintenance study improved quality of life, overall functioning, and sleep quality in patients with GAD.Keywords: atypical antipsychotic, anxiety disorders, quality of life, sleep quality, functioning, randomized studies

  9. Profile of once-daily darunavir/cobicistat fixed-dose combination for the treatment of HIV/AIDS

    Directory of Open Access Journals (Sweden)

    Navarro J

    2016-10-01

    Full Text Available Jordi Navarro, Adrian Curran Infectious Diseases Department, Hospital Universitari Vall d’Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain Abstract: Efficacy is the main objective of antiretroviral treatment and adherence is one of the cornerstones to achieve it. For this reason, treatment simplification is of key importance with regard to antiretroviral regimens. Rezolsta® (darunavir/cobicistat is the first fixed-dose combination containing a protease inhibitor approved for HIV treatment. This coformulation includes darunavir, a protease inhibitor that has shown its efficacy and safety in naïve and treatment-experienced patients, and cobicistat, the new pharmacokinetic enhancer that is expected to replace ritonavir. Bioequivalence between ritonavir and cobicistat as darunavir boosters has been shown in studies involving healthy volunteers. Furthermore, efficacy and safety of darunavir/cobicistat observed in phase III studies, including naïve and pretreated patients without darunavir-associated resistance mutations, are comparable to historical data of darunavir/ritonavir 800/100 mg once-daily formulation. Adverse events with darunavir/cobicistat are scarce and mild, and basically include skin reactions and gastrointestinal disturbances. Although small increases in plasma creatinine are expected in patients receiving cobicistat due to the inhibition of creatinine transporters in kidney tubules, actual glomerular filtrate rate remains unaltered. Cobicistat does not have an inducer effect on metabolic pathways and shows much more selective inhibition than ritonavir. Therefore, isoenzyms different from CYP3A4 are supposed to be less affected by cobicistat, and thus fewer drug–drug interactions are expected. Keywords: darunavir, cobicistat, fixed-dose combination, HIV infection, antiretroviral treatment

  10. Twice-daily versus once-daily antiretroviral therapy and coformulation strategies in HIV-infected adults: benefits, risks, or burden?

    Directory of Open Access Journals (Sweden)

    Nachega JB

    2011-12-01

    Full Text Available Jean B Nachega1–3, Bernd Rosenkranz4, Paul A Pham51Department of International Health, 2Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; 3Department of Medicine and Centre for Infectious Diseases, 4Division of Pharmacology, Department of Medicine, Faculty of Health Sciences, University of Stellenbosch, Capetown, South Africa; 5Department of Medicine, Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD, USAAbstract: The recent development of once-daily antiretroviral agents and fixed-dose combination formulations has been an important development in antiretroviral regimen simplification. Recent studies indicate that once-daily antiretroviral regimens improve adherence, especially in antiretroviral-naïve patients and in difficult-to-treat populations, such as the homeless or marginally housed. However, there are potential risks with the higher peak and lower trough plasma drug concentrations that may result from certain once-daily formulations. Due to the multifactorial and complex nature of adherence behavior, clinicians’ efforts to improve patient adherence should not be limited to prescribing once-daily regimens, but should also consider social support, side effect management, and adherence support tools, such as pillbox organizers and other targeted interventions. Additional research will clarify the benefits of once-daily and fixed-dose combination regimens on clinical and virologic outcomes. Comprehensive cost-benefit analysis of regimen simplification could help facilitate evidence-based decisions regarding antiretroviral regimen choices.Keywords: regimen adherence, regimen simplification, health care costs, fixed-dose combination, once-daily antiretroviral drugs

  11. Once-daily or twice-daily delivery of inhaled corticosteroids: assessment of the efficacy and of influence of the long term treatment on growth in asthmatic children

    Directory of Open Access Journals (Sweden)

    Lilijana Besednjak-Kocijančič

    2006-03-01

    Full Text Available Background: Inhaled corticosteroids are recommended drugs for asthma treatment. Their growth suppressive potential is well-known. Twice-daily delivery is usually used in children, but poor compliance of such long-term treatment may represent a problem which can be resolved with once-daily regimen. The aim of this prospective study was to asses the efficacy and the influence on growth of long term once-daily administration of inhaled fluticasone propionate (FP in asthmatic Slovene children under 5 years.Methods: Children with mild persistent asthma took part in parallel group trial. Their parents recorded asthma symptoms, β 2-agonist usage, and PEF using a form for asthma control on a daily basis for a period of one year. According twice or once-daily treatment they were divided in two groups: group A – children receiving FP 100 μg twice-daily and group B – children receiving FP 200 μg once-daily at bedtime. Mean height of 26 children of the same sex and age from each group and of 26 healthy children (groups A1, B1, C was observed. Chi-square analysis with Yates’ correction and t-tests were employed for between – group analyses (SPSS software 11.0.Results: FP given once-daily was as effective and tolerated as the same total dose given twice-daily. PEF, asthma symptoms and bronchodilator use of children from group B were not significantly different from those from group A (p > 0.05. The mean height increase of children receiving FP once-daily was smaller for 0.22 cm than of children receiving FP twice-daily and for 0.98 cm than of healthy children (t = 1.56, p = 0.132; DF: 24.Conclusions: Once-daily administration of inhaled FP in asthmatic children is safe and as effective as twice-daily administration. The suppressive potential is greater when it is given once-daily.

  12. Clinical benefit of fixed-dose dual bronchodilation with glycopyrronium and indacaterol once daily in patients with chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Ulrik, Charlotte Suppli

    2014-01-01

    (salmeterol/fluticasone twice daily), once-daily fixed-dose indacaterol/glycopyrronium has clinically important effects on symptoms, including dyspnea score, health status, level of lung function, and rate of moderate or severe exacerbations in patients with moderate-to-very severe COPD (Global initiative...

  13. Indacaterol 75 μg once daily for the treatment of patients with chronic obstructive pulmonary disease: a North American perspective.

    Science.gov (United States)

    Kerwin, Edward M; Williams, James

    2013-02-01

    Chronic obstructive pulmonary disease (COPD) is a progressive disease in which patients become increasingly disabled by their symptoms and limited in their activities. Health-related quality of life may be profoundly impaired even in the early stages of the disease. Treatment with long-acting inhaled bronchodilators can improve lung function, symptoms and health status and reduce exacerbations of COPD. This review profiles the efficacy, safety and tolerability of indacaterol, an inhaled β(2)-agonist bronchodilator for once-daily maintenance treatment of patients with COPD. After 12 weeks of treatment with a once-daily dose of 75 µg (the dose approved in the USA and Canada) in patients with moderate to severe COPD, compared with placebo, indacaterol provided significant and clinically relevant levels of bronchodilation [difference in trough forced expiratory volume in 1 s: 131 ml; 95% confidence interval (CI) 104-159; p indacaterol 75 µg for 12 weeks did not differ in any substantial aspect from placebo treatment. Indirect comparisons analyzing pooled clinical data and meta-analyses suggest that treatment with indacaterol 75 µg once daily may be effective in reducing exacerbations of COPD, and that its effects on lung function and health status will be comparable with other currently available inhaled long-acting bronchodilators used for COPD. Treatment with indacaterol 75 µg once daily provides effective bronchodilation, improves dyspnea and health status, and has a well characterized profile of safety and tolerability.

  14. The safety and effectiveness of once daily detemir in patients with type 2 diabetes previously failing oral agents:the Chinese cohort from SOL-VETM observational study

    Institute of Scientific and Technical Information of China (English)

    潘长玉

    2013-01-01

    Objective To evaluate the safety and effectiveness of initiating once-daily insulin detemir(Levemir) as add-on therapy in patients with type 2 diabetes mellitus(T2DM) who failed treatment of oral anti-diabetic drugs(OAD).Methods The present study was derived from the data of

  15. Adherence to GLP-1 receptor agonist therapy administered by once-daily or once-weekly injection in patients with type 2 diabetes in Germany

    Directory of Open Access Journals (Sweden)

    Qiao Q

    2016-06-01

    Full Text Available Qing Qiao,1 Mario JNM Ouwens,1 Susan Grandy,2 Kristina Johnsson,1 Karel Kostev3 1Global Medicines Development, AstraZeneca, Gothenburg, Sweden; 2Global Medicines Development, AstraZeneca, Gaithersburg, MD, USA; 3Epidemiology and Evidence-Based Medicine, Real-World Evidence Solutions, IMS Health, Frankfurt am Main, Germany Aim: This study aimed to compare 6-month adherence to therapy with exenatide once weekly (Bydureon® vs liraglutide once daily (Victoza® in patients with type 2 diabetes under primary care in Germany.Methods: A nationwide longitudinal prescription database (LRx, (between January 2011 and September 2014 was used to analyze adherence to therapy. The proportion of days covered (PDC by prescription was used as a measure of adherence in the 6-month postindex period. Logistic regression analyses were performed to investigate the associations between glucagon-like peptide-1 receptor agonist therapy adjusting for age, sex, and cotherapy.Results: Therapy was initiated in 5,449 patients with exenatide once weekly (age: 59.7±11.8 years; 51.4% were male and in 24,648 patients with liraglutide once daily (age: 59.4±11.4 years; 49.7% were male. The median PDC was 0.88 for exenatide once weekly and 0.77 for liraglutide once daily (P<0.05. Once-weekly exenatide was associated with significantly higher adherence. Odds ratio (95% confidence interval for having a PDC of ≥0.80 was 1.78 (1.62–1.96 for exenatide once weekly compared with liraglutide once daily after adjusting for age, sex, and cotherapy.Conclusion: Adherence to treatment with exenatide once weekly was significantly increased compared to that with liraglutide once daily over 6 months in patients with type 2 diabetes. Keywords: type 2 diabetes, GLP-1 receptor agonists, adherence

  16. Pharmacokinetics and tolerability of daptomycin at doses up to 12 milligrams per kilogram of body weight once daily in healthy volunteers.

    Science.gov (United States)

    Benvenuto, Mark; Benziger, David P; Yankelev, Sara; Vigliani, Gloria

    2006-10-01

    Daptomycin, a novel lipopeptide, is bactericidal against a broad range of gram-positive strains, including methicillin- (MRSA) and vancomycin-resistant Staphylococcus aureus. Daptomycin is approved at 4 mg/kg of body weight given intravenously once daily for the treatment of complicated skin and skin structure infections and at 6 mg/kg for the treatment of S. aureus bloodstream infections (bacteremia), including right-sided endocarditis caused by methicillin-susceptible S. aureus and MRSA. The present study was designed to evaluate the multiple-dose pharmacokinetics and safety of daptomycin at doses of 6 to 12 mg/kg in healthy volunteers. Three cohorts of 12 subjects each were given daptomycin (10 mg/kg) or placebo once daily for 14 days, daptomycin (12 mg/kg) or placebo once daily for 14 days, or daptomycin (6 or 8 mg/kg) once daily for 4 days. Daptomycin produced dose-proportional increases in the area under the plasma concentration-time curve and in trough daptomycin levels and nearly dose-proportional increases in peak daptomycin concentrations. Other pharmacokinetic parameters measured on day 1 and at steady state were independent of the dose, including the half-life (approximately 8 h), weight-normalized plasma clearance (9 to 10 ml/h/kg), and volume of distribution (approximately 100 ml/kg). Plasma protein binding was 90% to 93% and was independent of the daptomycin concentration. Daptomycin did not produce electrocardiographic abnormalities or electrophysiological evidence of muscle or nerve toxicity. Daptomycin was well tolerated in subjects dosed with up to 12 mg/kg intravenously for 14 days. Doses of daptomycin higher than 6 mg/kg once daily may be considered in further studies to evaluate the safety and efficacy of daptomycin in difficult-to-treat infections.

  17. Turning a molecule into a medicine: the development of indacaterol as a novel once-daily bronchodilator treatment for patients with COPD.

    Science.gov (United States)

    Murphy, Lorraine; Rennard, Stephen; Donohue, James; Molimard, Mathieu; Dahl, Ronald; Beeh, Kai-Michael; Dederichs, Juergen; Fülle, Hans-Jürgen; Higgins, Mark; Young, David

    2014-09-01

    Indacaterol is the first once-daily, long-acting β2-adrenergic agonist (LABA) approved for the treatment of chronic obstructive pulmonary disease (COPD). Indacaterol was developed using a combination of informed drug design and molecular chemistry to generate a β2-adrenergic agonist with a fast onset and long duration of action, enabling once-daily dosing with an acceptable safety profile. Early preclinical studies with indacaterol demonstrated these characteristics, and this promising molecule was taken into clinical development, originally for asthma treatment. Subsequent safety concerns over LABA monotherapy in patients with asthma redirected indacaterol's development to centre on COPD, where a good evidence base and guideline recommendations for bronchodilator monotherapy existed. Clinical development was initially complicated by different inhaler devices and differing doses of indacaterol. Using a phase III innovative adaptive-design clinical trial (INHANCE), indacaterol 150 and 300 μg once-daily doses were selected to be taken forward into the phase III INERGIZE programme. This programme delivered placebo-controlled and active-comparator data, including comparisons with formoterol, tiotropium and salmeterol/fluticasone, as well as the use of indacaterol in combination with tiotropium. Together, these studies provided a comprehensive assessment of the benefit-risk profile of indacaterol, allowing for regulatory submission. Indacaterol was first approved at once-daily doses of 150 and 300 μg in the European Union in 2009, followed by 150 µg in Japan (2011) and China (2012), and 75 μg in the United States (2011). To date, indacaterol is approved and marketed in more than 100 countries worldwide for once-daily maintenance treatment of COPD.

  18. Pharmacodynamics and Pharmacokinetics Following Once-Daily and Twice-Daily Dosing of Tiotropium Respimat® in Asthma Using Standardized Sample-Contamination Avoidance

    Science.gov (United States)

    Kirsten, Anne-Marie; Dusser, Daniel; Sharma, Ashish; Cornelissen, Piet; Sigmund, Ralf; Moroni-Zentgraf, Petra; Dahl, Ronald

    2016-01-01

    Abstract Background: This study was conducted to confirm the 24-hour bronchodilator efficacy and pharmacokinetic profile of once-daily tiotropium Respimat® 5 μg add-on to inhaled corticosteroids (ICS) in adults with symptomatic asthma. It used a trial protocol designed to minimize the risk of pharmacokinetic sample contamination resulting from improper sampling procedure, sample handling, or device handling during priming and subsequent inhalation procedure. Methods: A Phase II, randomized, double-blind, two-way crossover study (NCT01696071) comparing two daily dosing regimens of tiotropium for 4 weeks, once-daily 5 μg (evening dosing) or twice-daily 2.5 μg (morning and evening dosing), as add-on to maintenance therapy with ICS (400–800 μg budesonide or equivalent) as controller medication. There was no washout between treatment periods. Results: An increase in the area under the curve of the 24-hour forced expiratory volume in 1 second profile from study baseline was observed following once-daily tiotropium 5 μg (217 mL) and twice-daily 2.5 μg (219 mL), with no difference between the two regimens (−2 mL [95% confidence interval: −38, 34]). In a subset of the study population, total tiotropium exposure, expressed as area under the plasma concentration versus time curve over 24 hours, was comparable between dosing regimens. Unexpected tiotropium plasma levels were observed in two patients, possibly because of contamination. Conclusions: The observed bronchodilator efficacy over 24 hours was similar with once-daily tiotropium 5 μg and twice-daily 2.5 μg as add-on to ICS therapy, supporting the suitability of once-daily dosing to provide sustained improvements in lung function in adults with symptomatic asthma. PMID:26859538

  19. CSF LPV concentrations and viral load in viral suppressed patients on LPV/r monotherapy given once daily

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    Juan Tiraboschi

    2014-11-01

    Full Text Available Introduction: Plasma trough concentrations of lopinavir (LPV given as LPV/r 800/200 mg once daily (OD are reduced in comparison with 400/100 mg twice daily (BID. While OD dosage of LPV/r is sufficient to achieve viral suppression in plasma, data about drug penetration and viral suppression in central nervous system (CNS is needed, mainly if LPVr is used as maintenance monotherapy strategy in selected patients. The objective of this study was to evaluate CSF HIV-1 RNA and CSF LPV concentrations in patients receiving LPV/r monotherapy OD (LPVrMOD. Material and Methods: This is a cross-sectional sub-study within a prospective, open-label pilot simplification study to evaluate the efficacy and safety of LPV/rMOD in virologically suppressed patients previously receiving a BID LPV/r monotherapy regimen (LPV/rMBID, the “Kmon study” (NCT01581853. To assess LPV concentrations and HIV-1 RNA in CSF, a lumbar puncture (LP was performed in a subgroup of patients after at least one month of LPVrMOD treatment. Plasma-paired samples of all patients were also obtained. HIV-1 RNA was determined by real-time PCR (limit of detection 40 copies/mL. Liquid chromatography-tandem mass spectrometry (Tandem labs, NJ was used to determine CSF and blood plasma LPV concentrations. Results: Nine patients were included. Median (range age was 48 (34–56 years, median CD4 cell count 672 (252–1,408 cells/mL, median nadir CD4 count 125 (35–537 cells/mL and 40% of subjects were HCV-positive. Before starting LPV/rMOD median time on a LPV/r-containing regimen and on LPV/rMBID were 9 (4–11 years and 15 (7–24 months respectively, median time with undetectable HIV viral load was 5 (3–12 years and 2 patients had a previous documented blip. LP was performed a median of 24 (8–36 weeks after starting LPV/rMOD and 24 (11–28 hours after the last LPV/rMOD dose CSF and plasma HIV RNA was 40 copies/mL in all patients. Median LPV CSF concentration was 9.78 (1.93–78.3 ng

  20. POSSIBLE ADVERSE EFFECTS OF ONCE-DAILY ORAL THERAPEUTIC DOSE OF EITHER GLUCOSAMINE SULFATE OR GLUCOSAMINE/CHONDROITIN SULFATE ON BLOOD CELLS COUNT IN RATS

    Directory of Open Access Journals (Sweden)

    Noushi Abeer Amer

    2013-10-01

    Full Text Available This study was designed to investigate the possible adverse effects that may be induced by once-daily therapeutic doses of either glucosamine sulfate or glucosamine/chondroitin sulfate administered orally to rats for 30 days on blood cells (RBCs, WBCs and platelets counts. Forty three white healthy adult Albino rats of both sexes were selected randomly for this study. They were divided into three groups (І, ІІ, ІІІ. Group І received 0.05 ml distilled water, group ІІ received once daily therapeutic dose of glucosamine sulphate and group ІІІ received once daily therapeutic dose of glucosamine sulphate/chondroitin sulphate orally. The treatment period was for 30 days. At day 31, the animals were subjected to light ether anaesthesia and blood was withdrawn from the eye by retro-orbital puncture for the estimation of blood cells (RBCs, WBCs and platelets count. Treatment with single daily therapeutic dose of either GS alone or GS/CS for 30 days on blood cells count in rats produced a non significant change in RBCs counts compared to control and to each other. There were no statistically significant differences in total WBCs count at day 31 in animals administered once daily therapeutic dose of either GS or GS/CS orally compared to control group. In contrast, there was a statistically significant elevation in total WBCs count in GS/CS- treated rats compared to that in the GS-treated rats. The results of this study also showed that there was statistically significant decrease in neutrophils percentage in both drug treatment groups compared to control group. A statistically significant reduction in the percentage of monocytes was observed in GS/CS group compared to the corresponding percentage in animals of control group; while, there were non-significant differences in the percentage of monocytes in GS treated rats compared to that in the control group. There were no significant differences in the percentage of monocytes at day 31 of GS

  1. Changes in mammary uptake and metabolic fate of glucose with once-daily milking and feed restriction in dairy cows

    OpenAIRE

    Guinard-Flament, Jocelyne; Delamaire, Eloise; Lemosquet, Sophie; Boutinaud, Marion; David, Yolande

    2006-01-01

    International audience; The aim of this review is to better understand the regulation of milk yield in response to once-daily milking and feed restriction. Glucose is the principal precursor for the synthesis of lactose (a major osmotic agent in milk), and participates in determining the milk volume produced. When applying these two breeding factors, reductions in milk yield are associated with a reduction in milk lactose yield and in the arterial flow of glucose, due to a decrease in the mam...

  2. Efficacy of indacaterol 75 μg once-daily on dyspnea and health status: results of two double-blind, placebo-controlled 12-week studies.

    Science.gov (United States)

    Gotfried, Mark H; Kerwin, Edward M; Lawrence, David; Lassen, Cheryl; Kramer, Benjamin

    2012-12-01

    Indacaterol is an inhaled, once-daily, long-acting ®(2)-agonist for the treatment of COPD. Most previous studies were conducted with doses of 150 and/or 300 μg once-daily, and data with the 75 μg dose are limited. Two identically designed studies were, therefore, conducted to evaluate the efficacy and safety of the 75 μg once-daily dose. In two double-blind studies conducted in the USA, patients with moderate-to-severe COPD were randomized to treatment with indacaterol 75 μg once-daily (n = 163 and 159) or matching placebo (n = 160 and 159) for 12 weeks. The primary variable was forced expiratory volume in 1 s measured 24 h post-dose after 12 weeks (reported elsewhere). This report describes secondary efficacy endpoints, including transition dyspnea index (TDI) and St George's Respiratory Questionnaire (SGRQ) total scores, and the percentages of patients with improvements of or above the minimal clinically important difference (MCID; ≥1 in TDI score and ≥4 in SGRQ score). Differences between indacaterol and placebo for TDI total score at week 12 were 1.23 (p indacaterol at week 12 (2.0 and 0.9 with placebo), with odds ratios for achieving the MCID of 1.80 (p = 0.024) and 1.71 (p = 0.031). Patients receiving indacaterol had statistically significant or numerical improvements in diary-derived symptom variables compared with placebo. Treatment with indacaterol 75 μg may provide useful improvements in patient-reported outcomes in patients with moderate-to-severe COPD.

  3. Sustained 24-hour efficacy of once daily indacaterol (300 μg) in patients with chronic obstructive pulmonary disease: a randomized, crossover study.

    Science.gov (United States)

    Laforce, Craig; Aumann, Joseph; de Teresa Parreño, Luis; Iqbal, Amir; Young, David; Owen, Roger; Higgins, Mark; Kramer, Benjamin

    2011-02-01

    Indacaterol is a novel, once daily, inhaled ultra-long-acting β₂-agonist for the treatment of chronic obstructive pulmonary disease (COPD). Here we compared the 24-h spirometry profile of once daily indacaterol 300 μg with that of placebo and twice daily salmeterol 50 μg in patients with COPD. This randomized, multicenter, placebo-controlled, crossover study comprised three 14-day treatment periods (with 14-day washouts). Patients (male/female ≥ 40 years) with moderate-to-severe COPD were randomized to receive double-blind indacaterol 300 μg or placebo once daily, or open-label salmeterol 50 μg twice daily. The primary outcome measure was 24-h post-dose (trough) FEV₁ (mean of FEV₁ at 23 h 10 min and 23 h 45 min post-indacaterol dose) after 14 days. FEV₁ was assessed at multiple time points on Days 1 and 14 of each treatment period. Safety and tolerability were also monitored. Of 68 randomized patients, 61 completed. Trough FEV₁ (primary endpoint) on Day 14 for indacaterol was 200 mL higher than placebo (p indacaterol was 150 mL higher than placebo (p Indacaterol provided superior bronchodilation compared with placebo (p indacaterol provided superior FEV₁ compared with salmeterol (p indacaterol 300 μg produced effective sustained 24-h bronchodilation from the first dose, an efficacy profile superior to placebo and twice daily salmeterol. Given its effective bronchodilation with once daily dosing, indacaterol is likely to be a useful treatment option for patients with moderate-to-severe COPD. Copyright © 2010 Elsevier Ltd. All rights reserved.

  4. Efficacy, Safety and Pharmacokinetics of Once-Daily Saquinavir Soft-Gelatin Capsule/Ritonavir in Antiretroviral-Naive, HIV-Infected Patients

    Directory of Open Access Journals (Sweden)

    Julio Montaner SG

    2006-05-01

    Full Text Available Abstract Context Once-daily HIV treatment regimens are being used in clinical practice with the objective of improving patient acceptance and adherence. Objective To evaluate the efficacy and safety of saquinavir-soft-gelatin capsule (SGC/ritonavir combination (1600 mg/100 mg vs efavirenz (600 mg both once daily and combined with 2 nucleoside analogs twice daily. Setting Twenty-six centers in the United States, Canada, and Puerto Rico. Patients A total of 171 antiretroviral naive HIV-infected individuals were enrolled in a 48-week, phase 3, open-label, randomized study. Main Outcome Measure Proportion of patients with HIV-RNA levels Results In the primary intent-to-treat population at week 48, 51% (38/75 and 71% (55/77 of patients in the saquinavir-SGC/ritonavir and efavirenz groups, respectively, achieved HIV-RNA suppression P = .5392, 95% 1-sided confidence interval [CI] = -33.5%. In the on-treatment (OT population, 73% (38/52 and 93% (54/58 of patients in the saquinavir-SGC/ritonavir and efavirenz groups, respectively, had effective viral suppression P = .5015, 95% 1-sided CI = -33.4%. Mean CD4+ cell counts increased by 239 and 204 cells/microliters (mcL, in the saquinavir-SGC/ritonavir and efavirenz groups, respectively, in the OT analysis (P = .058. Both regimens were reasonably well tolerated, although more gastrointestinal adverse events were reported with saquinavir-SGC/ritonavir. Pharmacokinetic profiles in 6 patients showed an observed median Cmin at 24 hours of 429 ng/mL (range, 68-1750 ng/mL. Conclusion Once-daily efavirenz was statistically superior to once-daily saquinavir-SGC/ritonavir. Gastrointestinal adverse effects were commonly associated with treatment failure in the saquinavir-SGC/ritonavir arm of the study.

  5. A randomized, single-blind trial of 5% minoxidil foam once daily versus 2% minoxidil solution twice daily in the treatment of androgenetic alopecia in women.

    Science.gov (United States)

    Blume-Peytavi, Ulrike; Hillmann, Kathrin; Dietz, Ekkehart; Canfield, Douglas; Garcia Bartels, Natalie

    2011-12-01

    Although twice-daily application of propylene glycol-containing 2% minoxidil topical solution (MTS) stimulates new hair growth, higher concentrations of minoxidil in a once-daily, propylene glycol-free formulation may improve efficacy and reduce unpleasant side effects. We sought to compare the efficacy, safety, and acceptability and to show noninferiority of once-daily 5% minoxidil topical foam (MTF) with twice-daily 2% MTS in women with androgenetic alopecia. A total of 113 women with androgenetic alopecia were randomized to 24 weeks of treatment with 5% MTF or 2% MTS. The primary efficacy parameter was change from baseline in nonvellus target area hair count at week 24. Secondary end points included change in nonvellus target area hair width, overall efficacy by global photographic review as assessed by treatment-blinded evaluators and the subject herself, adverse events, and participants' assessment of product aesthetics. After 24 weeks, women randomized to 5% MTF once daily showed noninferior target area hair count and target area hair width and experienced greater, but nonsignificant, improvements in target area hair count, target area hair width, and overall efficacy by global photographic review than those randomized to 2% MTS used twice daily. 5% MTF was significantly superior to 2% MTS in participants' agreement with "the treatment does not interfere with styling my hair" (P = .002). Women randomized to 5% MTF experienced significantly lower rates of local intolerance (P = .046) especially in pruritus and dandruff compared with 2% MTS. Because of differences in the formulations tested, study participants were not blinded to treatment. Once-daily 5% MTF is noninferior and as effective for stimulating hair growth as twice-daily 2% MTS in women with androgenetic alopecia and is associated with several aesthetic and practical advantages. Copyright © 2010 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

  6. Once-daily oral administration of cyclosporine in a lung transplant patient with a history of renal toxicity of calcineurin inhibitors.

    Science.gov (United States)

    Matsuda, Yuya; Chen, Fengshi; Miyata, Hitomi; Date, Hiroshi

    2014-07-01

    Cyclosporine is usually administered orally in two divided doses every 12 h in transplant patients. However, some patients have difficulty in achieving therapeutic levels after transplantation. In fact, cyclosporine is reportedly administered once daily in renal and liver transplantation cases, but not in lung transplantation cases. We report a patient with a history of calcineurin inhibitor-induced renal toxicity who successfully underwent living-donor lobar lung transplantation (LDLLT) with the novel immunosuppressive strategy of once-daily administration of cyclosporine. An 18-year old man with progressive respiratory insufficiency after bone marrow transplantation was referred to our hospital for lung transplantation. He had a history of renal toxicity due to calcineurin inhibitors. Based on his history of tacrolimus- and cyclosporine-induced renal toxicity, we decided to initiate basiliximab as induction therapy, followed by once-daily cyclosporine administration to obtain high enough blood cyclosporine concentrations at 2 h post-dose (C2) and lowered trough blood concentrations (C0) for protection of renal function as maintenance therapy. LDLLT was successfully performed, and the postoperative course was uneventful and free of rejection episodes. Cyclosporine dosing was adjusted with intensive therapeutic drug monitoring of blood cyclosporine levels. One year after LDLLT, the patient is alive and well with no problems with daily life activities. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  7. Compliance, clinical outcome, and quality of life of patients with stable angina pectoris receiving once-daily betaxolol versus twice daily metoprolol: a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Przemyslaw Kardas

    2007-05-01

    Full Text Available Przemyslaw KardasThe First Department of Family Medicine, Medical University of LodzBackground: A randomized, controlled trial was conducted in an outpatient setting to examine the effect of beta-blocker dosing frequency on patient compliance, clinical outcome, and health-related quality of life in patients with stable angina pectoris.Methods: One hundred and twelve beta-blockers-naive outpatients with stable angina pectoris were randomized to receive betaxolol, 20 mg once daily or metoprolol tartrate, 50 mg twice daily for 8 weeks. The principal outcome measure was overall compliance measured electronically, whereas secondary outcome measures were drug effectiveness and health-related quality of life.Results: The overall compliance was 86.5 ± 21.3% in the betaxolol group versus 76.1 ± 26.3% in the metoprolol group (p < 0.01, and the correct number of doses was taken on 84.4 ± 21.6% and 64.0 ± 31.7% of treatment days, respectively (p < 0.0001. The percentage of missed doses was 14.5 ± 21.5% in the once-daily group and 24.8 ± 26.4% in the twice-daily group (p < 0.01. The percentage of doses taken in the correct time window (58.6% vs 42.0%, p = 0.01, correct interdose intervals (77.4% v 53.1%, p < 0.0001, and therapeutic coverage (85.6% vs 73.7%, p < 0.001 were significantly higher in the once-daily group. Both studied drugs had similar antianginal effectiveness. Health-related quality of life improved in both groups, but this increase was more pronounced in the betaxolol arm in some dimensions.Conclusions: The study demonstrates that patient compliance with once-daily betaxolol is significantly better than with twice daily metoprolol. Similarly, this treatment provides better quality of life. These results demonstrate possible therapeutic advantages of once-daily over twice-daily beta-blockers in the treatment of stable angina pectoris.Keywords: patient compliance, quality of life, stable angina pectoris, randomized controlled trial

  8. Induction of oxidative DNA damage by mesalamine in the presence of copper: a potential mechanism for mesalamine anticancer activity.

    Science.gov (United States)

    Zimmerman, Ryan P; Jia, Zhenquan; Zhu, Hong; Vandjelovic, Nathan; Misra, Hara P; Wang, Jianmin; Li, Yunbo

    2011-02-27

    Mesalamine is the first line pharmacologic intervention for patients with ulcerative colitis, and recent epidemiologic studies have demonstrated a protective association between therapeutic use of the drug and colorectal carcinoma. However, the mechanism by which this protection is afforded has yet to be elucidated. Because copper is found at higher than normal concentrations in neoplastic cell nuclei and is known to interact with phenolic compounds to generate reactive oxygen species, we investigated whether the reaction of mesalamine/copper was able to induce oxidative DNA strand breaks in φX-174 RF I plasmid DNA, and the various components of the mechanism by which the reaction occurred. Plasmid DNA strand breaks were induced by pharmacologically relevant concentrations of mesalamine in the presence of a micromolar concentration of Cu(II), and damage was inhibited by bathocuproinedisulfonic acid (BCS) and catalase. Further, we showed that the reaction of copper with mesalamine consumed molecular oxygen, which was inhibited by BCS. Electron paramagnetic resonance spectral analysis of the reaction of copper/mesalamine indicated the presence of the hydroxyl radical, which was inhibited by both BCS and catalase. This study demonstrates for the first time that through a copper-redox cycling mechanism, the copper-mediated oxidation of mesalamine is a pro-oxidant interaction that generates hydroxyl radicals which may participate in oxidative DNA damage. These results demonstrate a potential mechanism of the anticancer effects of mesalamine in patients with ulcerative colitis.

  9. Acute respiratory failure secondary to mesalamine-induced interstitial pneumonitis.

    Science.gov (United States)

    Abraham, Albin; Karakurum, Ali

    2013-08-20

    Interstitial pneumonitis as an adverse effect of mesalamine therapy is a rare but potentially serious complication. Patients typically have a mild disease course with no documented cases of respiratory failure in published literature. Given its variable latent period and non-specific signs and symptoms, it may be difficult to diagnose. We present the case of a 65-year-old man who presented with symptoms of fever, shortness of breath and a non-productive cough, 2 weeks after initiation of therapy with mesalamine. His hospital course was complicated by acute respiratory failure requiring intubation and mechanical ventilation. Radiographic studies revealed bilateral lower lobe infiltrates and bronchosopy with bronchoalveolar lavage and transbronchial biopsy were consistent with a diagnosis of drug-induced interstitial pneumonitis. The aim of this paper is to highlight the importance of considering a diagnosis of mesalamine-induced lung injury in patients presenting with respiratory symptoms while on mesalamine therapy and to review relevant literature.

  10. Cardiac MRI-confirmed mesalamine-induced myocarditis.

    Science.gov (United States)

    Baker, William L; Saulsberry, Whitney J; Elliott, Kaitlyn; Parker, Matthew W

    2015-09-04

    A 38-year-old Caucasian man with a medical history significant for inflammatory bowel disease (IBD) and mesalamine use presented to the emergency department with stabbing, pleuritic, substernal chest pain over the previous 2 days. Findings of leucocytosis, elevated cardiac enzymes and inflammatory markers, T-wave or ST-segment abnormalities and left ventricular systolic dysfunction suggested mesalamine-induced myocarditis. However, a cardiac MRI confirmed the diagnosis. Signs and symptoms improved within days of withdrawal of mesalamine, and initiation of corticosteroids and follow-up studies within the next year were unremarkable. Importantly, the diagnosis of mesalamine-induced myocarditis confirmed via cardiac MRI is a step rarely performed in published cases.

  11. Comparison of two once-daily regimens with a regimen consisting of nelfinavir, didanosine, and stavudine in antiretroviral therapy-naive adults : 48-week results from the antiretroviral regimen evaluation study (ARES)

    NARCIS (Netherlands)

    Lowe, SH; Wensing, AMJ; Hassink, EAM; ten Kate, RW; Richter, C; Schreij, G; Koopmans, PP; Juttmann, J.; van der Tweel, I.; Lange, JMA; Borleffs, JCC

    2005-01-01

    Background: To improve the dosing frequency and pill burden of antiretroviral therapy, we compared two once-daily dosed regimens to a twice-daily dosed regimen. Method: HIV-1-infected, antiretroviral drug-naive adults were randomized to either twice-daily nelfinavir and stavudine and once-daily dida

  12. Comparison of two once-daily regimens with a regimen consisting of nelfinavir, didanosine, and stavudine in antiretroviral therapy-naive adults: 48-week results from the Antiretroviral Regimen Evaluation Study (ARES).

    NARCIS (Netherlands)

    Lowe, S.H.; Wensing, B.M.; Hassink, E.A.M.; Kate, R.W. ten; Richter, C.; Schreij, G.; Koopmans, P.P.; Juttmann, J.R.; Tweel, I. van de; Lange, J.M.A.; Borleffs, J.C.

    2005-01-01

    BACKGROUND: To improve the dosing frequency and pill burden of antiretroviral therapy, we compared two once-daily dosed regimens to a twice-daily dosed regimen. METHOD: HIV-1-infected, antiretroviral drug-naive adults were randomized to either twice-daily nelfinavir and stavudine and once-daily dida

  13. Tadalafil once daily and extracorporeal shock wave therapy in the management of patients with Peyronie's disease and erectile dysfunction: results from a prospective randomized trial.

    Science.gov (United States)

    Palmieri, A; Imbimbo, C; Creta, M; Verze, P; Fusco, F; Mirone, V

    2012-04-01

    Extracorporeal shock wave therapy improves erectile function in patients with Peyronie's disease. However, erectile dysfunction still persists in many cases. We aimed to investigate the effects of extracorporeal shock wave therapy plus tadalafil 5 mg once daily in the management of patients with Peyronie's disease and erectile dysfunction not previously treated. One hundred patients were enrolled in a prospective, randomized, controlled study. Patients were randomly allocated to receive either extracorporeal shock wave therapy alone for 4 weeks (n = 50) or extracorporeal shock wave therapy plus tadalafil 5 mg once daily for 4 weeks (n = 50). Main outcome measures were: erectile function (evaluated through the shortened version of the International Index of Erectile Function), pain during erection (evaluated through a Visual Analog Scale), plaque size, penile curvature and quality of life (evaluated through an internal questionnaire). Follow-up evaluations were performed after 12 and 24 weeks. In both groups, at 12 weeks follow-up, mean Visual Analog Scale score, mean International Index of Erectile Function score and mean quality of life score ameliorated significantly while mean plaque size and mean curvature degree were unchanged. Intergroup analysis revealed a significantly higher mean International Index of Erectile Function score and quality of life score in patients receiving the combination. After 24 weeks, intergroup analysis revealed a significantly higher mean International Index of Erectile Function score and mean quality of life score in patients that received extracorporeal shock wave therapy plus tadalafil. In conclusion extracorporeal shock wave therapy plus tadalafil 5 mg once daily may represent a valid conservative strategy for the management of patients with Peyronie's disease and erectile dysfunction.

  14. Clinical benefit of fixed-dose dual bronchodilation with glycopyrronium and indacaterol once daily in patients with chronic obstructive pulmonary disease: a systematic review

    Directory of Open Access Journals (Sweden)

    Ulrik CS

    2014-04-01

    Full Text Available Charlotte Suppli UlrikDepartment of Respiratory Medicine, Hvidovre Hospital and University of Copenhagen, Hvidovre, DenmarkBackground and aim: Long-acting bronchodilators are the preferred option for maintenance therapy of patients with chronic obstructive pulmonary disease (COPD. The aim of this review is to provide an overview of the clinical studies evaluating the clinical efficacy of the once-daily fixed-dose dual bronchodilator combination of indacaterol and glycopyrronium bromide in patients suffering from COPD.Methods: This study comprised a systematic review of randomized controlled trials identified through systematic searches of different databases of published trials.Results: Nine trials (6,166 participants were included. Fixed-dose once-daily indacaterol/glycopyrronium seems to be safe and well tolerated in patients with COPD. Compared with single therapy with other long-acting bronchodilators (indacaterol, glycopyrronium, and tiotropium and fixed-combination long-acting β2-agonist/inhaled corticosteroid (salmeterol/fluticasone twice daily, once-daily fixed-dose indacaterol/glycopyrronium has clinically important effects on symptoms, including dyspnea score, health status, level of lung function, and rate of moderate or severe exacerbations in patients with moderate-to-very severe COPD (Global initiative for chronic Obstructive Lung Disease [GOLD] spirometric criteria. Furthermore, a very recent study has shown that fixed-dose indacaterol/glycopyrronium improves exercise endurance time compared with placebo, although no significant difference was observed between fixed-dose indacaterol/glycopyrronium and tiotropium.Conclusion: Fixed-dose indacaterol/glycopyrronium has clinically relevant effects on important COPD outcome measures and is, in general, superior to therapy with a single long-acting bronchodilator (with or without inhaled corticosteroid indicating long-acting dual bronchodilation as a potential important maintenance

  15. Efficacy of a new once-daily long-acting inhaled beta2-agonist indacaterol versus twice-daily formoterol in COPD.

    Science.gov (United States)

    Dahl, Ronald; Chung, Kian Fan; Buhl, Roland; Magnussen, Helgo; Nonikov, Vladimir; Jack, Damon; Bleasdale, Patricia; Owen, Roger; Higgins, Mark; Kramer, Benjamin

    2010-06-01

    Indacaterol is a long-acting inhaled beta(2)-agonist (LABA) for the treatment of chronic obstructive pulmonary disease (COPD). In previous studies, indacaterol provided 24 h bronchodilation on once-daily dosing with a fast onset of action. This study compared the efficacy and safety of indacaterol with the twice-daily LABA formoterol and placebo over 1 year. Patients with moderate to severe COPD were randomised to receive once-daily indacaterol 300 microg (n=437) or 600 microg (n=428), twice-daily formoterol 12 microg (n=435) or placebo (n=432) for 52 weeks in a double-blind double-dummy parallel group study. The primary efficacy variable was forced expiratory volume in 1 s (FEV(1)) measured 24 h postdose after 12 weeks (indacaterol vs placebo). Other outcomes included dyspnoea (transition dyspnoea index, TDI), use of as-needed salbutamol, symptom-based measures recorded on diary cards, exacerbations, health status (St George's Respiratory Questionnaire), BODE index (body mass index, obstruction, dyspnoea, exercise), safety and tolerability. Indacaterol increased 24 h postdose FEV(1) after 12 weeks by 170 ml (both doses) versus placebo and by 100 ml versus formoterol (all pindacaterol was more effective than formoterol in improving TDI score and reducing the need for as-needed salbutamol. Indacaterol was well tolerated and had a good overall safety profile, including minimal impact on QTc interval and systemic beta(2)-mediated events. Once-daily indacaterol is an effective 24 h bronchodilator that improves symptoms and health status and confers clinical improvements over a twice-daily 12 h LABA as a treatment for patients with moderate to severe COPD. NCT 00393458.

  16. Clinical benefit of fixed-dose dual bronchodilation with glycopyrronium and indacaterol once daily in patients with chronic obstructive pulmonary disease: a systematic review.

    Science.gov (United States)

    Ulrik, Charlotte Suppli

    2014-01-01

    Long-acting bronchodilators are the preferred option for maintenance therapy of patients with chronic obstructive pulmonary disease (COPD). The aim of this review is to provide an overview of the clinical studies evaluating the clinical efficacy of the once-daily fixed-dose dual bronchodilator combination of indacaterol and glycopyrronium bromide in patients suffering from COPD. This study comprised a systematic review of randomized controlled trials identified through systematic searches of different databases of published trials. Nine trials (6,166 participants) were included. Fixed-dose once-daily indacaterol/glycopyrronium seems to be safe and well tolerated in patients with COPD. Compared with single therapy with other long-acting bronchodilators (indacaterol, glycopyrronium, and tiotropium) and fixed-combination long-acting β2-agonist/inhaled corticosteroid (salmeterol/fluticasone twice daily), once-daily fixed-dose indacaterol/glycopyrronium has clinically important effects on symptoms, including dyspnea score, health status, level of lung function, and rate of moderate or severe exacerbations in patients with moderate-to-very severe COPD (Global initiative for chronic Obstructive Lung Disease [GOLD] spirometric criteria). Furthermore, a very recent study has shown that fixed-dose indacaterol/glycopyrronium improves exercise endurance time compared with placebo, although no significant difference was observed between fixed-dose indacaterol/glycopyrronium and tiotropium. Fixed-dose indacaterol/glycopyrronium has clinically relevant effects on important COPD outcome measures and is, in general, superior to therapy with a single long-acting bronchodilator (with or without inhaled corticosteroid) indicating long-acting dual bronchodilation as a potential important maintenance therapeutic option for patients with symptomatic COPD, possibly also for the treatment of naïve patients.

  17. Pharmacodynamics and Pharmacokinetics Following Once-Daily and Twice-Daily Dosing of Tiotropium Respimat(®) in Asthma Using Standardized Sample-Contamination Avoidance

    DEFF Research Database (Denmark)

    Beeh, Kai-Michael; Kirsten, Anne-Marie; Dusser, Daniel;

    2016-01-01

    BACKGROUND: This study was conducted to confirm the 24-hour bronchodilator efficacy and pharmacokinetic profile of once-daily tiotropium Respimat(®) 5 μg add-on to inhaled corticosteroids (ICS) in adults with symptomatic asthma. It used a trial protocol designed to minimize the risk...... of pharmacokinetic sample contamination resulting from improper sampling procedure, sample handling, or device handling during priming and subsequent inhalation procedure. METHODS: A Phase II, randomized, double-blind, two-way crossover study (NCT01696071) comparing two daily dosing regimens of tiotropium for 4...

  18. Use of new once-daily 5-aminosalicylic acid preparations in the treatment of ulcerative colitis: Is there anything new under the sun?

    Institute of Scientific and Technical Information of China (English)

    Peter Laszlo Lakatos

    2009-01-01

    5-aminosalicylate (5-ASA) agents remain the mainstay treatment in ulcerative colitis (UC). A number of oral 5-ASA agents are commercially available, including azobond pro-drugs, as well as delayed- and controlledrelease forms of mesalazine. However, poor adherence due to frequent daily dosing and a large number of tablets has been shown to be an important barrier to successful management of patients with UC. Recently, new, once-daily formulations of mesalazine, including the unique multi-matrix delivery system and mesalazine granules, were proven to be efficacious in inducing and maintaining remission in mild-to-moderate UC, with a good safety profile comparable to that of other oral mesalazine formulations. In addition, they offer the advantage of a low pill burden and might contribute to increased long-term compliance and treatment success in clinical practice. This editorial summarizes the available literature on the short- and medium-term efficacy and safety of the new once-daily mesalazine formulations.

  19. Bronchodilator efficacy and safety of indacaterol 150 μg once daily in patients with COPD: an analysis of pooled data.

    Science.gov (United States)

    Bleecker, Eugene R; Siler, Thomas; Owen, Roger; Kramer, Benjamin

    2011-01-01

    Indacaterol is an inhaled, once-daily long-acting β(2)-agonist bronchodilator for regular use in patients with chronic obstructive pulmonary disease (COPD). As indacaterol is the first once-daily β(2)-agonist to be developed, it is relevant to evaluate its bronchodilator efficacy, safety, and tolerability. Data were pooled from three randomized, double-blind, clinical studies in patients with moderate-to-severe COPD treated with indacaterol 150 μg qd (n = 627) or placebo (n = 1021). Bronchodilator efficacy was assessed as trough (24-hour post-dose) forced expiratory volume in 1 second (FEV(1)) after 12 weeks (primary endpoint in individual studies) and FEV(1) measured serially post-dose. Rescue use of albuterol was monitored. At week 12, indacaterol increased trough FEV(1) by 160 mL compared with placebo (P indacaterol than with placebo (P indacaterol recorded 53% of days without use of rescue albuterol, compared with 38% of days in the placebo group (P indacaterol and placebo, respectively, and serious adverse events for 4% and 5%. Worsening of COPD was the most frequent adverse event (10% indacaterol; 15% placebo). Indacaterol had little effect on pulse or blood pressure or measures of systemic β(2)-adrenoceptor activity (blood glucose, serum potassium, and corrected QT interval). Indacaterol was an effective bronchodilator and was well tolerated, with a good safety profile over 12 weeks of treatment. It should prove a useful treatment for patients with moderate-to-severe COPD.

  20. Comparison of airway dimensions with once daily tiotropium plus indacaterol versus twice daily Advair(®) in chronic obstructive pulmonary disease.

    Science.gov (United States)

    Hoshino, Makoto; Ohtawa, Junichi; Akitsu, Kenta

    2015-02-01

    Current guidelines recommend combining long-acting bronchodilators with different modes of action in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD). We evaluated the effects of airway dimensions and pulmonary function with tiotropium plus indacaterol versus Advair(®). Subjects (n = 46) were randomized to receive tiotropium (18 μg once daily) plus indacaterol (150 μg once daily) or Advair(®) (50/250 μg twice daily) for 16 weeks. Airway geometry was determined by quantitative computed tomography (luminal area, Ai; total area of the airway, Ao; wall area, WA; and percentage wall area, WA/Ao and wall thickness, T). Spirometry (forced expiratory volume in 1 s, FEV1; forced vital capacity, FVC and inspiratory capacity, IC) and St. George's Respiratory Questionnaire (SGRQ) were evaluated. Tiotropium plus indacaterol significantly increased CT-indices including Ai corrected for body surface area (Ai/BSA), and decreased WA/BSA, WA/Ao and T/√BSA compared with Advair(®) (p indacaterol than Advair(®) (p indacaterol than Advair(®). These findings suggest that dual bronchodilation with tiotropium plus indacaterol is superior in airway geometry and lung function compared with Advair(®) in COPD. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Spotlight on fluticasone furoate/vilanterol trifenatate for the once-daily treatment of asthma: design, development and place in therapy

    Science.gov (United States)

    Albertson, Timothy E; Bullick, Samuel W; Schivo, Michael; Sutter, Mark E

    2016-01-01

    The use of inhaled corticosteroids (ICSs) plays a key role in the treatment of asthmatic patients, and international guidelines have designated ICSs as an early maintenance therapy in controlling asthma symptoms. When asthmatic patients remain symptomatic on ICSs, one common option is to add a long-acting beta2 agonist (LABA) to the maintenance treatment. Fixed combination inhalers that contain both an ICS and a LABA have been popular for both chronic obstructive pulmonary disease (COPD) and asthma. Historically, these inhalers have been dosed twice daily. However, currently, there is a once-daily combination therapy with the ICS fluticasone furoate (FF) and the LABA vilanterol trifenatate (VI) with indications for use in both COPD and asthma. This dry powder inhaler (DPI) comes in two doses of FF (100 or 200 μg) both combined with VI (25 μg). This article reviews the clinical trial data for FF, VI and FF/VI combination inhalers and documents the efficacy and safety of once-daily inhaled maintenance therapy by DPI in asthmatic patients. PMID:28008228

  2. Efficacy and safety of telithromycin 800 mg once daily for 7 days in community-acquired pneumonia: an open-label, multicenter study

    Directory of Open Access Journals (Sweden)

    Dunbar Lala M

    2005-05-01

    Full Text Available Abstract Background Community-acquired pneumonia (CAP remains a major cause of morbidity and mortality throughout the world. Telithromycin (a new ketolide has shown good in vitro activity against the key causative pathogens of CAP, including S pneumoniae resistant to penicillin and/or macrolides. Methods The efficacy and safety of telithromycin 800 mg orally once daily for 7 days in the treatment of CAP were assessed in an open-label, multicenter study of 442 adults. Results Of 149 microbiologically evaluable patients, 57 (9 bacteremic had Streptococcus pneumoniae. Of the 57 S pneumoniae pathogens isolated in these patients, 9 (2 bacteremic were penicillin- or erythromycin-resistant; all 57 were susceptible to telithromycin and were eradicated. Other pathogens and their eradication rates were: Haemophilus influenzae (96%, Moraxella catarrhalis (100%, Staphylococcus aureus (80%, and Legionella spp. (100%. The overall bacteriologic eradication rate was 91.9%. Of the 357 clinically evaluable patients, clinical cure was achieved in 332 (93%. In the 430 patients evaluable for safety, the most common drug-related adverse events were diarrhea (8.1% and nausea (5.8%. Conclusion Telithromycin 800 mg once daily for 7 days is an effective and well-tolerated oral monotherapy and offers a new treatment option for CAP patients, including those with resistant S pneumoniae.

  3. Use of new once-daily 5-aminosalicylic acid preparations in the treatment of ulcerative colitis: Is there anything new under the sun?

    Science.gov (United States)

    Lakatos, Peter Laszlo

    2009-04-21

    5-aminosalicylate (5-ASA) agents remain the mainstay treatment in ulcerative colitis (UC). A number of oral 5-ASA agents are commercially available, including azobond pro-drugs, as well as delayed- and controlled-release forms of mesalazine. However, poor adherence due to frequent daily dosing and a large number of tablets has been shown to be an important barrier to successful management of patients with UC. Recently, new, once-daily formulations of mesalazine, including the unique multi-matrix delivery system and mesalazine granules, were proven to be efficacious in inducing and maintaining remission in mild-to-moderate UC, with a good safety profile comparable to that of other oral mesalazine formulations. In addition, they offer the advantage of a low pill burden and might contribute to increased long-term compliance and treatment success in clinical practice. This editorial summarizes the available literature on the short- and medium-term efficacy and safety of the new once-daily mesalazine formulations.

  4. Exacerbation of Bloody Diarrhea as a Side Effect of Mesalamine Treatment of Active Ulcerative Colitis

    Directory of Open Access Journals (Sweden)

    Yuichi Shimodate

    2011-04-01

    Full Text Available Mesalamine has been used as the first-line therapy for the treatment of ulcerative colitis (UC because of its efficacy and fewer side effects. However, earlier study showed that mesalamine occasionally causes diarrhea. We are presenting a patient with active UC in whom bloody diarrhea accompanied by abdominal pain and fever occurred and the symptoms were aggravated after administration of mesalamine. In order to clarify the reason of symptoms aggravation, drug lymphocyte stimulation test and rechallenge trial with mesalamine were performed. The results indicated the possibility that aggravation was related to allergic reaction and was dose-dependent. Furthermore, we examined colonoscopic views but there was no remarkable change in before and after rechallenge trial. Based on the above result, the patient was diagnosed with mesalamine intolerance. In order to differentiate whether the exacerbation of bloody diarrhea is due to the side effects of the mesalamine or a true relapse of UC, taking careful history before and after increasing mesalamine dosage as well as being aware of side effects of mesalamine are required. Clinicians should be aware of diarrhea as a side effect of mesalamine particularly after onset of mesalamine formulation, change in mesalamine formulation, or change in mesalamine dose.

  5. Material designs and new physical properties in MX- and MMX-chain compounds

    CERN Document Server

    Yamashita, Masahiro

    2014-01-01

    This book details the structures, physical properties, theoretical treatments, applications, and perspectives of MX and MMX chain compounds for chemists and physicists. It also examines various photoinduced phase transitions and their dynamics.

  6. Transcriptome profiling of Xanthomonas campestris pv. campestris grown in minimal medium MMX and rich medium NYG.

    Science.gov (United States)

    Liu, Wei; Yu, Yan-Hua; Cao, Shi-Yuan; Niu, Xiang-Na; Jiang, Wei; Liu, Guo-Fang; Jiang, Bo-Le; Tang, Dong-Jie; Lu, Guang-Tao; He, Yong-Qiang; Tang, Ji-Liang

    2013-06-01

    Xanthomonas campestris pathovar campestris (Xcc) is the causal agent of black rot disease in cruciferous plants worldwide. Although the complete genomes of several Xcc strains have been determined, the gene expression and regulation mechanisms in this pathogen are far from clear. In this work, transcriptome profiling of Xcc 8004 grown in MMX medium (minimal medium for Xanthomonas campestris) and NYG medium (peptone yeast glycerol medium) were investigated by RNA-Seq. Using the Illumina HiSeq 2000 platform, a total of 26,514,630 reads (90 nt in average) were generated, of which 15,708,478 reads mapped uniquely to coding regions of Xcc 8004 genome. Of the 4273 annotated protein-coding genes of Xcc 8004, 629 were found differentially expressed in Xcc grown in MMX and NYG. Of the differentially expressed genes, 495 were up-regulated and 134 were down-regulated in MMX. The MMX-induced genes are mainly involved in amino acid metabolism, transport systems, atypical condition adaptation and pathogenicity, especially the type III secretion system, while the MMX-repressed genes are mainly involved in chemotaxis and degradation of small molecules. The global transcriptome analyzes of Xcc 8004 grown in MMX and NYG might facilitate the gene functional characterization of this phytopathogenic bacterium.

  7. Levofloxacin plus metronidazole administered once daily versus moxifloxacin monotherapy against a mixed infection of Escherichia coli and Bacteroides fragilis in an in vitro pharmacodynamic model.

    Science.gov (United States)

    Hermsen, Elizabeth D; Hovde, Laurie B; Sprandel, Kelly A; Rodvold, Keith A; Rotschafer, John C

    2005-02-01

    Moxifloxacin has been suggested as an option for monotherapy of intra-abdominal infections. Recent data support the use of a once-daily metronidazole regimen. The purpose of this study was to investigate the activity of levofloxacin (750 mg every 24 h [q24h]) plus metronidazole (1,500 mg q24h) compared with that of moxifloxacin (400 mg q24h) monotherapy in a mixed-infection model. By using an in vitro pharmacodynamic model in duplicate, Escherichia coli and Bacteroides fragilis were exposed to peak concentrations of 8.5 mg of levofloxacin/liter q24h, 32 mg of metronidazole/liter q24h, and 2 mg for moxifloxacin/liter q24h for 24 h. The activities of levofloxacin, metronidazole, moxifloxacin, and levofloxacin plus metronidazole were evaluated against E. coli, B. fragilis, and E. coli plus B. fragilis. The targeted half-lives of levofloxacin, metronidazole, and moxifloxacin were 8, 8, and 12 h, respectively. Time-kill curves were analyzed for time to 3-log killing, slope, and regrowth. Pre- and postexposure MICs were determined. The preexposure levofloxacin, metronidazole, and moxifloxacin MICs for E. coli and B. fragilis were 0.5 and 1, >64 and 0.5, and 1 and 0.25 mg/liter, respectively. Levofloxacin and moxifloxacin achieved a 3-log killing against E. coli and B. fragilis in all experiments, as did metronidazole against B. fragilis. Metronidazole did not decrease the starting inoculum of E. coli. The area under the concentration-time curve/MIC ratios for E. coli and B. fragilis were 171.7 and 85.9, respectively, for levofloxacin and 26 and 103.9, respectively, for moxifloxacin. Levofloxacin plus metronidazole exhibited the fastest rates of killing. The levofloxacin and moxifloxacin MICs for B. fragilis increased 8- to 16-fold after the organism was exposed to moxifloxacin. No other changes in the postexposure MICs were found. Levofloxacin plus metronidazole administered once daily exhibited activity similar to that of moxifloxacin against the mixed E. coli and B

  8. Increased adherence eight months after switch from twice daily calcineurin inhibitor based treatment to once daily modified released tacrolimus in heart transplantation

    Directory of Open Access Journals (Sweden)

    Doesch AO

    2013-10-01

    Full Text Available Andreas O Doesch,1 Susanne Mueller,1 Ceylan Akyol,1 Christian Erbel,1 Lutz Frankenstein,1 Arjang Ruhparwar,2 Philipp Ehlermann,1 Thomas J Dengler,3 Hugo A Katus11Department of Cardiology, University of Heidelberg, Heidelberg, Germany; 2Department of Cardiovascular Surgery, University of Heidelberg, Heidelberg, Germany; 3Department of Cardiology, SLK-Kliniken Heilbronn, Bad Friedrichshall, GermanyBackground: Modified-release tacrolimus (TAC is a new, once-daily oral formulation of the established immunosuppressive agent TAC. This study evaluated long-term patient adherence, as well as safety and efficacy, in stable patients after heart transplantation (HTx who switched from a conventional twice daily calcineurin inhibitor-based regimen (TAC or cyclosporine A [CsA] to a once-daily modified-release TAC regimen.Methods: Stable patients were switched from conventional TAC or CsA (twice-daily dosing to modified-release TAC (once-daily dosing according to manufacturer's recommendations using a pre-experimental design. Self-reported adherence was assessed at baseline and 8 months after the switch with the Basel Assessment of Adherence with Immunosuppressive Medication Scale (BAASIS. Additionally, routine laboratory values were analyzed 8 months after switch.Results: Of 76 patients (58 male, 18 female initially included, 72 were available for statistical analysis, as modified-release TAC was discontinued due to diarrhea in one patient and gastrointestinal discomfort in three patients. Overall nonadherence at baseline for any of the four BAASIS items was 75.0% versus 40.3% after 8 months (P<0.0001. After 8 months, adherence was improved in 41 patients (56.9%, unchanged in 27 (37.5%, and reduced in four patients (5.6%. The BAASIS visual analog scale score improved significantly from 87.0% ± 13.5% to 97.5% ± 5.7% (P<0.0001. No significant changes were observed for hematological, renal, or liver function parameters after 8 months (all P=not significant

  9. Steady-state pharmacokinetics of once-daily cyclobenzaprine extended release: a randomized, double-blind, 2-period crossover study in healthy volunteers.

    Science.gov (United States)

    Darwish, Mona; Hellriegel, Edward T

    2011-06-01

    The single-dose pharmacokinetic profile of cyclobenzaprine extended-release (CER) has been previously characterized and compared with the pharmacokinetics of cyclobenzaprine immediate-release (CIR) administered 3 times daily for 3 doses. The objective of this study was to characterize the multiple-dose pharmacokinetic properties of once-daily CER 30 mg and CIR 10 mg TID formulations in healthy volunteers. In this double-blind, single-center, 2-period crossover study, healthy subjects were randomized to dosing sequences with once-daily CER 30 mg or CIR 10 mg TID for 7 days. Subjects crossed over to the alternative regimen following a 14-day washout period. Pharmacokinetic assessments at steady state included area under the plasma cyclobenzaprine concentration-time curve over the dosing interval (AUC(0-τ,ss)), peak plasma cyclobenzaprine concentration (C(max,ss)), time to observed C(max) (T(max,ss)), observed minimum cyclobenzaprine concentration (C(min,ss)), average cyclobenzaprine concentration (C(avg,ss)), accumulation ratio (R(ac)), and terminal elimination half-life (t(½)). Tolerability and safety assessments were conducted. A total of 36 subjects were randomized; 34 completed both dosing periods (1 subject was lost to follow-up, 1 withdrew consent). Steady state was reached for CER 30 mg on day 7. Mean C(max,ss), C(min,ss), and C(avg,ss) were 41.1, 21.4, and 31.4 ng/mL, respectively. The median T(max,ss) for CER 30 mg was 7.0 hours, with a mean t(½) of 34.8 hours. At steady state, CER produced a sustained plasma cyclobenzaprine concentration with a single peak in plasma concentration during the 24-hour dose interval. The R(ac) for CER was 2.65. Because of a protocol violation (insufficient data), no steady-state pharmacokinetic assessments could be performed for CIR. Most adverse events were mild or moderate in intensity. Somnolence was the most frequently reported adverse event (100% of subjects) in those receiving CER, followed by dry mouth (58

  10. Assessment of analgesia in human chronic pain. Randomized double-blind crossover study of once daily repro-dose morphine versus MST continus.

    Science.gov (United States)

    Peat, S; Sweet, P; Miah, Y; Barklamb, M; Larsen, U

    1999-10-01

    This study evaluated Repro-Dose morphine (RDM; Reliadol from Nycomed Pharma), a new once daily controlled-release morphine formulation, against twice daily MST Continuous (MST) at steady state in patients with chronic opioid responsive pain. A randomized double-blind two-way crossover design was used to evaluate the efficacy and adverse effects of RDM once daily or MST twice daily, at the same total daily doses, in patients with chronic stable pain (dose range 20-120 mg per day). During the RDM limb of the study active drug was administered in the evening and placebo in the morning. Dextromoramide was provided as escape analgesia throughout the study. Following a 5-day screening period, during which stability of oral opioid dose was verified, patients underwent two 5-day treatment periods, (one MST, one RDM) in random sequence. Pain scores, escape analgesia requirements and side-effects were compared using data from days 3, 4 and 5 of each treatment period. Any events or medication changes occurring during the study period thought liable to influence analgesia were regarded as protocol violations. Overall assessment and period preference was assessed by direct questioning. RDM treatment was regarded as successful if the amount of escape medication required during the RDM period was equal to or less than that required during the MST period. Forty-seven patients were included in the study, of whom 40 completed both periods [the intention to treat (ITT) population], 31 in strict accordance with the protocol [the per protocol (PP) population]. Results were similar for both populations. There was no significant difference in pain scores or incidence of adverse events occurring during the MST and RDM periods. For the ITT population, requirements for escape medication during the RDM period were less than, equal to or greater than those recorded during the MST period for 14, 15, and 11 patients, respectively. Twenty-nine of 40 patients (72.5%) were therefore RDM treatment

  11. A novel once daily microparticulate dosage form comprising lansoprazole to prevent nocturnal acid breakthrough in the case of gastro-esophageal reflux disease: preparation, pharmacokinetic and pharmacodynamic evaluation.

    Science.gov (United States)

    Alai, Milind; Lin, Wen Jen

    2013-01-01

    The objective of this study was to formulate and evaluate the lansoprazole (LPZ)-loaded microparticles to prevent nocturnal acid breakthrough in the case of gastro-esophageal reflux disease (GERD). The microparticulate delivery system was prepared by solvent evaporation method using Eudragit RS100 as a matrix polymer followed by enteric coated with Eudragit S100 and hydroxypropyl methylcellulose phthalate HP55 using spray drying method. The enteric coated microparticles were stable in gastric pH condition. In vivo pharmacokinetic and pharmacodynamic studies in male Wistar rats demonstrated that enteric coated microparticles sustained release of LPZ and promoted ulcer healing activity. In other words, the microparticulate dosage form provided effective drug concentration for a longer period as compared to conventional extended release dosage form, and showed sufficient anti-acid secretion activity to treat acid related disorders including the enrichment of nocturnal acid breakthrough event based on a once daily administration.

  12. A Prospective Open-Label Multicentre Trial on the Use of 1 G, Once Daily Ceftriaxone in Lower Respiratory Tract Infections

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    Donald E Low

    1994-01-01

    in the study. Clinical cure and clinical improvement were achieved in 64.6 and 28.3% of the evaluable patients. respectively. Relapse of infection occurred in two patients (1.8%. and treatment failure was recorded in six cases (5.3%. Twelve patients (8.8% died clue to reasons unrelated to the sludy treatment. Three adverse event (hives, diarrhea and phlebitis at the injection site were possibly related to the study drug. A cross-Canada in vitro susceptibility surveillance study of bacterial pathogens. frequently the cause of pneumonia. found ceftriaxone to have minimal inhibitory concentrations in 90% of isolates that would support such a dosing regimen. with the exception of Enterobacter species. These rcsults support the use of 1 g, once daily ceftriaxone for the empirical treatment of pneumonia in those patients requiring hospitalization.

  13. [Effects of once-daily low-dose administration of sustained-release theophylline on airway inflammation and airway hyperresponsiveness in patients with asthma].

    Science.gov (United States)

    Terao, Ichiro

    2002-04-01

    Bronchial asthma is eosinophilic airway inflammation with enhanced airway responsiveness induced by eosinophilic granule proteins such as eosinophilic cationic protein (ECP) that are released from eosinophils. In the present study using 30 outpatients with mild to moderate asthma who had no history of treatment with steroid inhalation, we examined the effects of 4-week low-dose (200 mg/day) treatment with Uniphyl Tablets, a sustained-release theophylline formulated for once-daily dosing, on airway inflammation and airway hyperresponsiveness, as well as on respiratory function. Uniphyl Tablets significantly (p statistically significant (p V50 also showed statistically significant (p < 0.05) improvement. Mean blood theophylline concentration at the time the improvements were seen was 3.95 mg/mL. These results suggest that low-dose administration of Uniphyl Tablets has anti-airway inflammatory and anti-airway hyperresponsiveness effects in mild to moderate asthmatic patients.

  14. Legal, ethical, and economic implications of breaking down once-daily fixed-dose antiretroviral combinations into their single components for cost reduction.

    Science.gov (United States)

    Ramiro, Miguel A; Llibre, Josep M

    2014-11-01

    The availability of generic lamivudine in the context of the current economic crisis has raised a new issue in some European countries: breaking up the once-daily fixed-dose antiretroviral combinations (FDAC) of efavirenz/tenofovir/emtricitabine, tenofovir/emtricitabine, or abacavir/lamivudine, in order to administer their components separately, thereby allowing the use of generic lamivudine instead of branded emtricitabine or lamivudine. The legal, ethical, and economic implications of this potential strategy are reviewed, particularly in those patients receiving a once-daily single-tablet regimen. An unfamiliar change in antiretroviral treatment from a successful patient-friendly FDAC into a more complex regimen including separately the components to allow the substitution of one (or some) of them for generic surrogates (in the absence of a generic bioequivalent FDAC) could be discriminatory because it does not guarantee access to equal excellence in healthcare to all citizens. Furthermore, it could violate the principle of non-maleficence by potentially causing harm both at the individual level (hindering adherence and favouring treatment failure and resistance), and at the community level (hampering control of disease transmission and transmission of HIV-1 resistance). Replacing a FDAC with the individual components of that combination should only be permitted when the substituting medication has the same qualitative and quantitative composition of active ingredients, pharmaceutical form, method of administration, dosage and presentation as the medication being replaced, and a randomized study has demonstrated its non-inferiority. Finally, a strict pharma-economic study supporting this change, comparing the effectiveness and the cost of a specific intervention with the best available alternative, should be undertaken before its potential implementation.

  15. Effectiveness and tolerance of single tablet versus once daily multiple tablet regimens as first-line antiretroviral therapy - Results from a large french multicenter cohort study

    Science.gov (United States)

    Cotte, Laurent; Ferry, Tristan; Pugliese, Pascal; Valantin, Marc-Antoine; Allavena, Clotilde; Cabié, André; Poizot-Martin, Isabelle; Rey, David; Duvivier, Claudine; Cheret, Antoine; Dellamonica, Pierre; Pradat, Pierre; Parienti, Jean-Jacques

    2017-01-01

    Objectives Pill burden during antiretroviral treatment (ART) is associated with worse adherence and impaired virological suppression. We compared the effectiveness, tolerance, and persistence on treatment of single tablet regimens (STRs) with non-STR once-daily regimens in patients receiving first-line ART. Methods Retrospective analysis of naïve HIV-1 infected patients prospectively enrolled in the French Dat’AIDS cohort and initiating first-line ART with STRs or once-daily non-STRs from 2004 to 2013. The primary outcome was time to treatment discontinuation defined by any change in the treatment regimen. STR and non-STR groups were compared controlling for baseline risk factors by inverse probability weighted treatment Cox analysis (IPWT) and propensity-score matching (PSM). Results Overall, 3212 patients (STR 499, non-STR 2713) were included. Median time to treatment discontinuation was shorter in non-STR patients than in STR patients, both in the IPWT (HR = 0.61, pPSM cohort (HR = 0.55, pPSM cohort (HR = 0.91, p = 0.33). A lower rate of virological failure was observed with STRs than with non-STRs in both cohorts (HR = 0.23; p = 0.002 and HR = 0.22, p = 0.003, respectively). A lower rate of treatment modification for adverse event was observed with non-STRs in the IPWT cohort (HR = 1.46, pPSM cohort (HR = 1.22, p = 0.11). Conclusion First-line therapy with STRs was associated with a longer time to treatment discontinuation than with non-STRs. However, when ART modification for simplification was not considered as a failure, STRs and non-STRs were similar. PMID:28152047

  16. Spotlight on fluticasone furoate/vilanterol trifenatate for the once-daily treatment of asthma: design, development and place in therapy

    Directory of Open Access Journals (Sweden)

    Albertson TE

    2016-12-01

    Full Text Available Timothy E Albertson,1–3 Samuel W Bullick,1,3 Michael Schivo,1 Mark E Sutter2,3 1Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, 2Department of Emergency Medicine, School of Medicine, UC Davis, Sacramento, 3Department of Medicine, Veterans Administration Northern California Health Care System, Mather, CA, USA Abstract: The use of inhaled corticosteroids (ICSs plays a key role in the treatment of asthmatic patients, and international guidelines have designated ICSs as an early maintenance therapy in controlling asthma symptoms. When asthmatic patients remain symptomatic on ICSs, one common option is to add a long-acting beta2 agonist (LABA to the maintenance treatment. Fixed combination inhalers that contain both an ICS and a LABA have been popular for both chronic obstructive pulmonary disease (COPD and asthma. Historically, these inhalers have been dosed twice daily. However, currently, there is a once-daily combination therapy with the ICS fluticasone furoate (FF and the LABA vilanterol trifenatate (VI with indications for use in both COPD and asthma. This dry powder inhaler (DPI comes in two doses of FF (100 or 200 µg both combined with VI (25 µg. This article reviews the clinical trial data for FF, VI and FF/VI combination inhalers and documents the efficacy and safety of once-daily inhaled maintenance therapy by DPI in asthmatic patients. Keywords: fluticasone furoate/vilanterol trifenatate, asthma, long-acting beta2 agonist, inhaled corticosteroid, combined inhaler, persistent asthma, dry powder inhaler  

  17. Mesalamine in the treatment and maintenance of remission of ulcerative colitis.

    Science.gov (United States)

    Ham, Maggie; Moss, Alan C

    2012-03-01

    Ulcerative colitis (UC) is a chronic disease of the GI tract that is characterized by mucosal inflammation in the colon. Mesalamine (mesalazine) is a 5-aminosalicylic acid compound that is the first-line treatment for patients with mild-to-moderate UC. There are multiple formulations of mesalamine available, primarily differentiated by their means of delivering active mesalamine to the colon. Mesalamine has been demonstrated in randomized controlled trials to induce both clinical response and remission, and maintain clinical remission, in these patients. It has few serious adverse effects and is generally well tolerated by patients. The main areas of uncertainty with use of mesalamine in patients with UC center on the optimal dose for induction of response, how to maintain patient adherence and the role of mesalamine in cancer chemoprophylaxis. Generic forms of mesalamine have yet to be approved by regulatory bodies in the USA.

  18. Once daily baclofen sustained release or gastro-retentive system are acceptable alternatives to thrice daily baclofen immediate release at same daily dosage in patients

    Directory of Open Access Journals (Sweden)

    Sampat Nitin

    2009-01-01

    Full Text Available Background: Baclofen, a GABA-agonist, is currently available as an immediate release (IR formulation for relieving neurogenic spasticity in a variety of disorders. Baclofen IR requires to be administered three times a day which inadvertently increases the chances of medication noncompliance among patients and is also associated with side effects such as drowsiness and muscle weakness. Aim: To overcome the shortcomings of baclofen IR, two modified formulations, baclofen sustained release (SR and gastric retentive system (GRS, have been proposed to be equivalent in efficacy to baclofen IR with the administration of a single daily dose. Materials and Methods: Ninety patients with chronic neurogenic muscular spasticity were enrolled requiring 10-20 mg of baclofen IR every eight hours. The patients were randomized to two treatment arms: SR (n = 46 or GRS (n = 44 at the same once-daily dose for four weeks. Efficacy was measured by Ashworth score for muscle tone, spasm score, reflex score, 30-item functional independence score, and patient′s diary score for three most affected activities of daily life. Results: The mean Ashworth score changed significantly (P = 0.00 for patients in the SR group from 3.03-2.69 (-0.35 and 3.07-2.70 (-0.37 for patients in the GRS group. There was no significant difference (P = 0.87 between baseline-adjusted Ashworth score reductions on SR (-0.35 and GRS (-0.37. Similar results were obtained for spasm, reflex, and functional independence scores. The mean baseline-adjusted patient-diary scores did not differ significantly between 8 am, 12 pm, 4 pm, and 8 pm (P = 0.96, either on SR (-5.3 to -6.1 or GRS (-7.3 to -8.1, indicating a uniform effect round-the-day on both. Further, sedation scores (mean ± SEM decreased significantly (P < 0.05 on both SR (10.36 ± 1.37 to 6.18 ± 0.92 and GRS (8.14 ± 1.57 to 5.33 ± 1.11, suggesting better toleration. Conclusion: Once-daily baclofen SR and GRS are efficacious, convenient, and

  19. Similar risk reduction of death of extended-release metoprolol once daily and immediate-release metoprolol twice daily during 5 years after myocardial infarction.

    Science.gov (United States)

    Herlitz, J; Dellborg, M; Karlson, B W; Lindqvist, J; Sandèn, W; Svensson, H; Sjölin, M; Wedel, H

    1999-04-01

    The pooled results from five placebo-controlled postinfarction studies with metoprolol have shown a significant reduction in total mortality. All five studies used immediate-release metoprolol twice daily. An extended-release formulation of metoprolol for once-daily use has since been developed. The aim of the present study was to compare the two different forms of metoprolol with regard to the risk reduction of death for 5 years postinfarction and to analyze whether treatment with the beta-blocker metoprolol is associated with a reduced mortality after the introduction of modern therapies such as thrombolysis, aspirin, and ACE inhibitors. All patients discharged after an acute myocardial infarction (AMI) from Sahlgrenska University Hospital (SU) during 1986-1987 (n = 740, Period I) and during 1990-1991 (n = 1446, Period II) from both SU and Ostra Hospital, Göteborg, Sweden, were included in the study. During Period I, 56% were prescribed immediate-release metoprolol compared with 61% prescribed extended-release metoprolol during Period II. Immediate-release metoprolol was not available for outpatient use during Period II. In a multivariate analysis, all variables significantly associated with either increased or decreased postinfarction mortality during Periods I and II (univariate analysis of patient characteristics, medical history, complications during the AMI medication at discharge) studied were with Cox's proportional hazards model. Treatment with immediate-release metoprolol was significantly associated with reduced mortality over 5 years during Period I (relative risk reduction for total mortality, -34%, P = 0.003; 95% CI for RR, 0.51-0.87), and treatment with extended-release metoprolol was significantly associated with reduced mortality during Period II (-34%, P metoprolol given once daily was associated with a similar risk reduction of death over 5 years as immediate-release metoprolol given twice daily. The data, furthermore, indicate that the beta

  20. Efficacy and safety of olodaterol once daily delivered via Respimat® in patients with GOLD 2–4 COPD: results from two replicate 48-week studies

    Directory of Open Access Journals (Sweden)

    Ferguson GT

    2014-06-01

    Full Text Available Gary T Ferguson,1 Gregory J Feldman,2 Peter Hofbauer,3 Alan Hamilton,4 Lisa Allen,5 Lawrence Korducki,5 Paul Sachs6 1Pulmonary Research Institute of Southeast Michigan, Livonia, MI, 2S Carolina Pharmaceutical Research, Spartanburg, SC, USA; 3Pneumologie, Weinheim, Germany; 4Boehringer Ingelheim, Burlington, ON, Canada; 5Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, 6Pulmonary Associates of Stamford, Stamford, CT, USA Background: Olodaterol is a long-acting β2-agonist with a 24-hour bronchodilator profile. Two replicate, randomized, double-blind, placebo-controlled, parallel-group, Phase III trials were performed as part of a comprehensive clinical program to investigate the long-term safety and efficacy of olodaterol in patients with moderate to very severe chronic obstructive pulmonary disease (COPD receiving usual-care background therapy. Methods: Patients received olodaterol 5 µg or 10 µg or placebo once daily for 48 weeks. Coprimary end points were forced expiratory volume in 1 second (FEV1 area under the curve from 0 to 3 hours (AUC0–3 response (change from baseline, and trough FEV1 response at 12 weeks. Secondary end points included additional lung function assessments, use of rescue medications, FEV1 AUC response from 0 to 12 hours, and Patient Global Rating over 48 weeks. Results: Overall, 624 and 642 patients were evaluated in studies 1222.11 and 1222.12, respectively. In both studies, olodaterol 5 µg and 10 µg significantly improved the FEV1 AUC0–3 response (P<0.0001 and trough FEV1 (study 1222.11, P<0.0001; study 1222.12, P<0.05, post hoc at week 12, with an incidence of adverse events comparable with that of placebo. Secondary end points supported the efficacy of olodaterol. Conclusion: These studies demonstrate the long-term efficacy and safety of once-daily olodaterol 5 µg and 10 µg in patients with moderate to very severe COPD continuing with usual-care maintenance therapy. Keywords: chronic obstructive

  1. Effects of changing milk replacer feedings from twice to once daily on Holstein calf innate immune responses before and after weaning.

    Science.gov (United States)

    Hulbert, L E; Cobb, C J; Carroll, J A; Ballou, M A

    2011-05-01

    The objectives of this study were to determine the effects of switching Holstein calves to once-daily feeding during the fourth week of life (24 ± 2.3 d of age; once-fed n=22; twice-fed n=22) on innate immune responses, and to evaluate whether carry-over effects occurred when the calves were weaned during the seventh week of life. Peripheral blood samples were taken immediately before the change in feeding strategy (24 d of age) and at 27, 31, 45, 48, 52, and 66 d of age and were analyzed for circulating cortisol, haptoglobin, total leukocyte counts, neutrophil:mononuclear cells, and hematocrit percentage. Heparinized whole blood was also stimulated with lipopolysaccharide (LPS) for 24h and the concentration of tumor necrosis factor-α (TNF-α) in the supernatant was analyzed. Neutrophil L-selectin and β(2)-integrin expression were analyzed by flow cytometry. Simultaneous neutrophil phagocytic and oxidative burst responses to a heat-killed Escherichia coli were quantified by dual-color flow-cytometry. Treatment (once-daily or twice daily feeding) had no effect on pre- or postweaning performance. Once-fed calves tended to have more circulating neutrophils at 27 d of age, greater expression of L-selectin on neutrophils at 31 and 45 d of age, and greater intensity of phagocytosis at 45 d of age. Once-fed calves secreted less TNF-α in LPS-stimulated whole blood cultures at 45 d of age compared with twice-fed calves and this tended to persist through the immediate postweaning period. None of the other immune parameters differed after weaning between the preweaning feeding strategies. Consolidating calf milk replacer into one feeding during the fourth week of life was likely a mild and acute stressor, as evidenced by transient neutrophilia in the absence of suppressed functional capacities of neutrophils. Future research should address the mechanism and immunological significance of the persistent decreased TNF-α response in once-fed calves.

  2. Review of Efficacy and Safety of Duloxetine 40 to 60 mg Once Daily in Patients with Diabetic Peripheral Neuropathic Pain

    Directory of Open Access Journals (Sweden)

    Vladimir Skljarevski

    2012-01-01

    Full Text Available We summarize efficacy and safety findings from 4 double-blind, placebo-controlled, 12-week studies and 1 open-label, uncontrolled, 34-week maintenance-of-effect (MOE study that examine duloxetine 40 and 60 mg once daily (QD in patients with diabetic peripheral neuropathic pain (DPNP. In all placebo-controlled studies, duloxetine showed significantly (P≤.01 greater reduction in pain severity (weekly mean of 24-hour average pain severity ratings, primary outcome measure compared with placebo. In all placebo-controlled studies, duloxetine showed significantly (P≤.05 greater improvement on brief pain inventory-Interference ratings. Patient global impression of improvement ratings were superior to placebo (P≤.01 for duloxetine patients in all placebo-controlled studies. Response rates (based on 30% pain reduction ranged from 57% to 68% for duloxetine and from 35% to 47% for placebo and were statistically significantly different (P≤.01 between treatment groups in 3 out of 4 studies. The open-label study showed maintenance of analgesic effect of duloxetine in DPNP. In the duloxetine groups, 4.3% to 14.9% of patients discontinued because of adverse events (placebo groups: 2.6% to 7.4%. Most commonly reported treatment-emergent adverse events were nausea, somnolence, and headache. Duloxetine 40 and 60 mg QD was efficacious and well tolerated in the management of DPNP.

  3. Effect of once-daily indacaterol in a predominantly Chinese population with chronic obstructive pulmonary disease: a 26-week Asia-Pacific study.

    Science.gov (United States)

    Yao, Wanzhen; Wang, Changzheng; Zhong, Nanshan; Han, Xiaowen; Wu, Changgui; Yan, Xixin; Chen, Ping; Yang, Wei; Henley, Michelle; Kramer, Benjamin

    2014-02-01

    This study, in a predominantly Chinese population, investigated the efficacy and safety of a once-daily (o.d.) inhaled ultra-long-acting β2 -agonist indacaterol for the treatment of moderate-to-severe chronic obstructive pulmonary disease (COPD). This is a 26-week, double-blind study on randomized patients who received indacaterol 150 μg or 300 μg or placebo o.d. The primary variable was trough forced expiratory volume in 1 s (FEV1 , average of 23 h 10 min and 23 h 45 min post-dose values) at Week 12. Health status (St George's Respiratory Questionnaire, SGRQ), dyspnoea (transition dyspnoea index, TDI) and safety were evaluated over 26 weeks. Of the 563 patients randomized, 561 (89.8% Chinese) received treatment and 482 completed. At Week 12, trough FEV1 improved significantly for indacaterol 150 and 300 μg versus placebo (1.32, 1.29 vs 1.17; P indacaterol 150 and 300 μg (0.82, 1.15; P Indacaterol delivered effective bronchodilation with significant improvements in breathlessness and health status in this predominantly Chinese population. © 2014 The Authors. Respirology © 2014 Asian Pacific Society of Respirology.

  4. Once daily administration of the SGLT2 inhibitor, empagliflozin, attenuates markers of renal fibrosis without improving albuminuria in diabetic db/db mice.

    Science.gov (United States)

    Gallo, Linda A; Ward, Micheal S; Fotheringham, Amelia K; Zhuang, Aowen; Borg, Danielle J; Flemming, Nicole B; Harvie, Ben M; Kinneally, Toni L; Yeh, Shang-Ming; McCarthy, Domenica A; Koepsell, Hermann; Vallon, Volker; Pollock, Carol; Panchapakesan, Usha; Forbes, Josephine M

    2016-05-26

    Blood glucose control is the primary strategy to prevent complications in diabetes. At the onset of kidney disease, therapies that inhibit components of the renin angiotensin system (RAS) are also indicated, but these approaches are not wholly effective. Here, we show that once daily administration of the novel glucose lowering agent, empagliflozin, an SGLT2 inhibitor which targets the kidney to block glucose reabsorption, has the potential to improve kidney disease in type 2 diabetes. In male db/db mice, a 10-week treatment with empagliflozin attenuated the diabetes-induced upregulation of profibrotic gene markers, fibronectin and transforming-growth-factor-beta. Other molecular (collagen IV and connective tissue growth factor) and histological (tubulointerstitial total collagen and glomerular collagen IV accumulation) benefits were seen upon dual therapy with metformin. Albuminuria, urinary markers of tubule damage (kidney injury molecule-1, KIM-1 and neutrophil gelatinase-associated lipocalin, NGAL), kidney growth, and glomerulosclerosis, however, were not improved with empagliflozin or metformin, and plasma and intra-renal renin activity was enhanced with empagliflozin. In this model, blood glucose lowering with empagliflozin attenuated some molecular and histological markers of fibrosis but, as per treatment with metformin, did not provide complete renoprotection. Further research to refine the treatment regimen in type 2 diabetes and nephropathy is warranted.

  5. Effects of once-daily extended release quetiapine fumarate (quetiapine XR) on quality of life and sleep in elderly patients with major depressive disorder.

    Science.gov (United States)

    Locklear, Julie C; Svedsäter, Henrik; Datto, Catherine; Endicott, Jean

    2013-07-01

    Major depressive disorder (MDD) is frequently associated with reduced quality of life (QoL) and sleep disturbance. We investigated the effects of once-daily extended release quetiapine fumarate (quetiapine XR) monotherapy on QoL and sleep in elderly patients with MDD. Prospectively planned analysis of patient-reported data from an 11-week (9-week randomized; 2-week post-treatment), double-blind, placebo-controlled, Phase III study. Elderly patients (≥66 years; DSM-IV MDD; Hamilton Rating Scale for Depression [HAM-D] total score ≥22, HAM-D Item 1 score ≥2) were randomized to quetiapine XR (flexible dosing 50-300 mg/day) or placebo. MADRS total score change from randomization at Week 9. Patient-reported outcomes: Quality of Life, Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF) % of maximum total score (Items 1-14), Q-LES-Q-SF Item 15 ('satisfaction with medication'), Q-LES-Q-SF Item 16 ('overall life satisfaction'), and Pittsburgh Sleep Quality Index (PSQI) global score. In total, 338 patients were randomized (166 quetiapine XR; 172 placebo). At Week 9, quetiapine XR significantly reduced MADRS total score (-16.33; difference: -7.54; 95% CI: -9.23, -5.85; pelderly patients with MDD. Copyright © 2013. Published by Elsevier B.V.

  6. An observational study to monitor the efficacy and tolerability of levofloxacin 500 mg once daily for treatment of chronic bacterial prostatitis in Saudi Arabia

    Science.gov (United States)

    El Meliegy, Amr Ismail; Torky, Mohammed

    2015-01-01

    Introduction: Chronic prostatitis is a common urological problem in men <50-year-old. Untypical uropathogens and an intact blood prostate barrier cause difficulty in using antibiotics to treat the infection. Patients and Methods: In this open-label, observational study, levofloxacin 500 mg was given once daily for 28 days for treatment of chronic prostatitis. The primary efficacy measurement was the disappearance of all pre-treatment symptoms. Efficacy analysis is based on the per protocol population (PPP), all other analyses use the intent to treat (ITT) population. Results: The ITT included 154 men and the PPP included 151 (results are for the ITT unless otherwise indicated). Mean age was 42 ± 9 years, common concomitant conditions were diabetes mellitus (7%) and hypertension (5%). All symptoms decreased at day 28. Notably, the rate of dysuria decreased from 86.1% to 10.6%, painful ejaculation from 71% to 2.6% and perineal discomfort from 60.3% to 7.3%. A cure of condition was identified in 58.9%. No treatment failures were reported. Physician-reported adherence to study medication was 96.8%. Conclusion: Levofloxacin appears to be an effective antibiotic for treating symptoms of chronic bacterial prostatitis. Levofloxacin was well-tolerated in this population. PMID:25657549

  7. Designing a biocompatible hydrogel for the delivery of mesalamine.

    Science.gov (United States)

    Neufeld, Lena; Bianco-Peled, Havazelet

    2015-08-01

    A new design for nanocomposite hydrogels based on cross-linked chitosan for the delivery of mesalamine is presented. To enhance drug loading in chitosan, the mineral montmorillonite was incorporated into the matrix. The exfoliated silica montmorillonite nanosheets form interactions with both chitosan and mesalamine, which affect the hydrogel's drug release mechanism and swelling properties. The impact of montmorillonite and glutaraldehyde concentrations on the hydrogel properties was investigated. In vitro drug-release studies detected slower release over short times when montmorillonite was introduced into the matrix. This study is the first to evaluate the influence of pH during mixing and on mixing duration. It was shown that lowering the pH during mixing delayed the release since the positively charged drug was better introduced between the montmorillonite layers, as confirmed by differential scanning calorimetry (DSC) and fourier transform infrared spectroscopy (FTIR) analysis. All hydrogels showed prolonged sustained release of mesalamine over 24h in simulated colonic fluid (pH 7.4). When modeled, the mesalamine release profile suggests a complex release mechanism, involving adsorption of the drug to the montmorillonite and its diffusion. The results imply that chitosan-montmorillonite hydrogels can serve as potential drug carriers for controlled-release applications.

  8. Efficacy and Safety of Once-Daily Minoxidil Foam 5% Versus Twice-Daily Minoxidil Solution 2% in Female Pattern Hair Loss: A Phase III, Randomized, Investigator-Blinded Study.

    Science.gov (United States)

    Blume-Peytavi, Ulrike; Shapiro, Jerry; Messenger, Andrew G; Hordinsky, Maria K; Zhang, Paul; Quiza, Carlos; Doshi, Uday; Olsen, Elise A

    2016-07-01

    A once-daily minoxidil topical foam (MTF) has been developed to treat female pattern hair loss. Determine noninferiority of once-daily 5% MTF versus twice-daily 2% minoxidil topical solution (MTS) based on the change from baseline in target area hair count (TAHC) at 24 weeks. In a randomized, phase III trial, women with female pattern hair loss received once-daily 5% MTF (n=161) or twice-daily 2% MTS (n=161) for 52 weeks. Primary endpoint was change from baseline in TAHC at 24 weeks. Secondary endpoint was change from baseline in TAHC at 12 weeks. Exploratory endpoints included change in total unit area density and change in overall scalp coverage. Once-daily 5% MTF increased TAHC from baseline (adjusted mean ± standard error) by 23.9 ± 2.1 hairs/cm2 at week 24. Twice-daily 2% MTS increased TAHC 24.2 ± 2.1 hairs/cm2 at week 24. The treatment difference was -0.3 hairs/cm2 (95% CI = -6.0, 5.4). Since the lower bound of the 95% CI was less than -5.0, the prespecified noninferiority goal was not met. Both treatments were well tolerated. Once-daily 5% MTF and twice-daily 2% MTS induced hair regrowth in female pattern hair loss, but prespecified noninferiority criteria were not met. ClinicalTrials.gov identifier: NCT01145625 J Drugs Dermatol. 2016;15(7):883-889.

  9. Exacerbation of Bloody Diarrhea as a Side Effect of Mesalamine Treatment of Active Ulcerative Colitis

    OpenAIRE

    Yuichi Shimodate; Kunihiro Takanashi; Eriko Waga; Tomoki Fujita; Shinichi Katsuki; Masafumi Nomura

    2011-01-01

    Mesalamine has been used as the first-line therapy for the treatment of ulcerative colitis (UC) because of its efficacy and fewer side effects. However, earlier study showed that mesalamine occasionally causes diarrhea. We are presenting a patient with active UC in whom bloody diarrhea accompanied by abdominal pain and fever occurred and the symptoms were aggravated after administration of mesalamine. In order to clarify the reason of symptoms aggravation, drug lymphocyte stimulation test and...

  10. Efficacy and safety of coadministration of once-daily indacaterol and glycopyrronium versus indacaterol alone in COPD patients: the GLOW6 study

    Directory of Open Access Journals (Sweden)

    Vincken W

    2014-02-01

    Full Text Available Walter Vincken,1 Joseph Aumann,2 Hungta Chen,3 Michelle Henley,3 Danny McBryan,4 Pankaj Goyal4 1Respiratory Division, University Hospital, UZ Brussel, Free University of Brussels, Brussels, Belgium; 2Longartsenpraktijk, Prins Bisschopssingel, Hasselt, Belgium; 3Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; 4Novartis Pharma AG, Basel, Switzerland Background: Addition of a second bronchodilator from a different pharmacological class may benefit patients with moderate-to-severe chronic obstructive pulmonary disease (COPD whose symptoms are insufficiently controlled by bronchodilator monotherapy. GLOW6 evaluated the efficacy and safety of once-daily coadministration of the long-acting β2-agonist indacaterol (IND and the long-acting muscarinic antagonist glycopyrronium (GLY versus IND alone in patients with moderate-to-severe COPD. Materials and methods: In this randomized, double-blind, parallel group, placebo-controlled, 12-week study, patients were randomized 1:1 to IND 150 µg and GLY 50 µg daily (IND + GLY or IND 150 µg daily and placebo (IND + PBO (all delivered via separate Breezhaler® devices. The primary objective was to demonstrate the superiority of IND + GLY versus IND + PBO for trough forced expiratory volume in 1 second (FEV1 at week 12. Other end points included trough FEV1 at day 1, FEV1 area under the curve from 30 minutes to 4 hours (AUC30min–4h, peak FEV1, inspiratory capacity and trough forced vital capacity (FVC at day 1 and week 12, and transition dyspnea index (TDI focal score, COPD symptoms, and rescue medication use over 12 weeks. Results: A total of 449 patients were randomized (IND + GLY, 226; IND + PBO, 223; 94% completed the study. On day 1 and at week 12, IND + GLY significantly improved trough FEV1 versus IND + PBO, with treatment differences of 74 mL (95% CI 46–101 mL and 64 mL (95% CI 28–99 mL, respectively (both P<0.001. IND + GLY significantly improved postdose peak FEV1, FEV1 AUC30min–4h

  11. Liraglutide: A review of its therapeutic use as a once daily GLP-1 analog for the management of type 2 diabetes mellitus

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    Mala Dharmalingam

    2011-01-01

    Full Text Available Type 2 diabetes mellitus (T2DM is a progressive disease associated with significant morbidity and mortality. Even though progress have been accomplished in the management of type 2 diabetes, current treatment preferences for patients with this disease still fall short to address disease progression. With the present therapy, glycaemic control remains suboptimal and are often associated with weight gain and hypoglycaemia. Glucagon like peptide-1 (GLP-1 is an incretin hormone secreted from the small intestine that lowers fasting and postprandial glucose through multiple mechanisms including glucose-dependent insulin secretion, reduction of glucagon secretion, delaying gastric emptying and increased satiety. Liraglutide, a human glucagon-like peptide 1 (GLP-1 analogue is a treatment for T2DM that is administered as a once-daily subcutaneous injection. The efficacy and tolerability of liraglutide at doses of 0.6, 1.2, and 1.8 mg for T2DM, in combination with, and compared with, other T2DM treatments were investigated in the Liraglutide Effect and Action in Diabetes (LEAD Phase III clinical trial program. In the LEAD trial, treatment with liraglutide was associated with substantial improvements in glycaemic control and low risk of hypoglycaemia. In addition liraglutide significantly improved β-cell function, reduced systolic blood pressure (BP and induced weight loss. Overall, liraglutide was well tolerated. Recent data on safety and efficacy of liraglutide from real-life clinical practice settings also reiterate the better therapeutic profile of this molecule. Based on results from the LEAD programme, and real-life clinical experience, liraglutide has been demonstrated as an effective therapeutic intervention even at the early stage of diabetes regardless of with what, it has been used.

  12. Once-daily glycopyrronium bromide, a long-acting muscarinic antagonist, for chronic obstructive pulmonary disease: a systematic review of clinical benefit

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    Ulrik CS

    2012-09-01

    Full Text Available Charlotte Suppli UlrikDepartment of Pulmonary Medicine, Hvidovre Hospital and University of Copenhagen, Copenhagen, DenmarkBackground: Long-acting bronchodilators are central in the pharmacological management of patients with chronic obstructive pulmonary disease (COPD. The aim of this systematic review is to provide an overview of the studies evaluating the safety and clinical efficacy of inhaled glycopyrronium bromide, a novel long-acting muscarinic antagonist, in patients with COPD.Methods: This study was performed as a systematic literature review.Results: Inhaled glycopyrronium bromide seems to be a safe and well tolerated long-acting muscarinic antagonist with a fast onset of action. In patients suffering from moderate to severe COPD, glycopyrronium bromide has clinically important effects on level of forced expiratory volume in one second, use of relief medication, percentage of days with no use of rescue medication, daytime dyspnea scores, and probably also on health status. Furthermore, in this group of patients, glycopyrronium bromide has beneficial effects on dynamic hyperinflation and exercise tolerance. Glycopyrronium bromide has been shown to reduce the rate of exacerbations in patients with moderate to severe COPD, but long-term controlled trials with exacerbation rate as the primary outcome variable have not been published yet.Conclusion: Once-daily inhaled glycopyrronium bromide has characteristics important for use in COPD, including a fast onset of action, sustained 24-hour bronchodilatation, and improvement in exercise tolerance, and therefore appears to have the potential for a significant role in the future management of COPD.Keywords: chronic obstructive pulmonary disease, glycopyrronium bromide, long-acting bronchodilators

  13. Formulation and In Vitro and In Vivo Evaluation of Lipid-Based Terbutaline Sulphate Bi-layer Tablets for Once-Daily Administration.

    Science.gov (United States)

    Hashem, Fahima M; Nasr, Mohamed; Fathy, Gihan; Ismail, Aliaa

    2016-06-01

    The objective of this study was to prepare and evaluate terbutaline sulphate (TBS) bi-layer tablets for once-daily administration. The bi-layer tablets consisted of an immediate-release layer and a sustained-release layer containing 5 and 10 mg TBS, respectively. The sustained-release layer was developed by using Compritol®888 ATO, Precirol® ATO 5, stearic acid, and tristearin, separately, as slowly eroding lipid matrices. A full 4 × 2(2) factorial design was employed for optimization of the sustained-release layer and to explore the effect of lipid type (X 1), drug-lipid ratio (X 2), and filler type (X 3) on the percentage drug released at 8, 12, and 24 h (Y 1, Y 2, and Y 3) as dependent variables. Sixteen TBS sustained-release matrices (F1-F16) were prepared by melt solid dispersion method. None of the prepared matrices achieved the targeted release profile. However, F2 that showed a relatively promising drug release was subjected to trial and error optimization for the filler composition to develop two optimized matrices (F17 and F18). F18 which consisted of drug-Compritol®888 ATO at ratio (1:6 w/w) and Avicel PH 101/dibasic calcium phosphate mixture of 2:1 (w/w) was selected as sustained-release layer. TBS bi-layer tablets were evaluated for their physical properties, in vitro drug release, effect of storage on drug content, and in vivo performance in rabbits. The bi-layer tablets showed acceptable physical properties and release characteristics. In vivo absorption in rabbits revealed initial high TBS plasma levels followed by sustained levels over 24 h compared to immediate-release tablets.

  14. Real-world glycemic outcomes in patients with type 2 diabetes initiating exenatide once weekly and liraglutide once daily: a retrospective cohort study

    Science.gov (United States)

    Saunders, William B; Nguyen, Hiep; Kalsekar, Iftekhar

    2016-01-01

    Aim The glucagon-like peptide-1 receptor agonists exenatide once weekly (QW) and liraglutide once daily (QD) have demonstrated improvements in glycemic outcomes in patients with type 2 diabetes mellitus in randomized clinical trials. However, little is known about their real-world comparative effectiveness. This retrospective cohort study used the Quintiles Electronic Medical Record database to evaluate the 6-month change in glycated hemoglobin (A1C) for patients initiating exenatide QW or liraglutide QD. Methods Patients with type 2 diabetes mellitus prescribed exenatide QW (n=664) or liraglutide QD (n=3,283) between February 1, 2012 and May 31, 2013 were identified. Baseline A1C measures were from 75 days before to 15 days after initiating exenatide QW or liraglutide QD, with follow-up measures documented at 6 months (±45 days). Adjusted linear regression models compared the difference in mean A1C change. A priori defined sensitivity analysis was performed in the subgroup of patients with baseline A1C ≥7.0% and no prescription for insulin during the 12-month pre-index period. Results For exenatide QW and liraglutide QD, respectively, mean (SD) age of the main study cohort was 58.01 (10.97) and 58.12 (11.05) years, mean (SD) baseline A1C was 8.4% (1.6) and 8.4% (1.6), and 48.2% and 54.2% of patients were women. In adjusted models, change in A1C did not differ between exenatide QW and liraglutide QD during 6 months of follow-up. Results were consistent in the subgroup analyses. Conclusion In a real-world setting, A1C similarly improves in patients initiating exenatide QW or liraglutide QD. PMID:27486339

  15. Effectiveness and safety of a long-acting, once-daily, two-phase release formulation of methylphenidate (Ritalin ® LA) in school children under daily practice conditions.

    Science.gov (United States)

    Haertling, Fabian; Mueller, Beate; Bilke-Hentsch, Oliver

    2015-06-01

    Long-acting (LA) preparations of methylphenidate allow for once-daily dosing; however, pharmacokinetics may vary and depend on food intake. The objective was to evaluate effectiveness of a two-phase release formulation (Ritalin(®) LA) under daily practice conditions. This was a prospective, multicenter, observational study in Germany. Eligibility and dosing were determined by the physician based on the drug label. Outcomes included changes over 3 months of treatment in assessments of effect duration, clinical global impression (CGI), and quality of life (ILK). In 101 sites, 262 patients (197 boys, 63 girls, and two unknown) with a mean age of 10.9 years were enrolled; 50 were treated for the first time; 212 switched medication to Ritalin(®) LA. After 3 months, CGI improved in 59.4 % of patients, and well-being overall was rated as good by 61.0 % of parents and 63.7 % of children. Based on parents' assessment, the proportion of children suffering from strong disease burden decreased from 40.7 to 15.1 %. In 123 insufficient responders to previous ADHD medications, benefit from Ritalin(®) LA was above average and effect duration was significantly prolonged as compared to pretreatment. Overall, 28 patients (10.7 %) had treatment-related adverse events with one case being serious; 23 patients (8.8 %) discontinued therapy, 7 (2.7 %) due to poor treatment response; and 212 patients (81 %) continued treatment beyond the study. In line with clinical trial data, Ritalin(®) LA provides significant benefit also under routine practice conditions.

  16. Once-daily indacaterol 75 μg in moderate- to-severe COPD: results of a Phase IV study assessing time until patients' perceived onset of effect.

    Science.gov (United States)

    Siler, Thomas M; LaForce, Craig F; Kianifard, Farid; Williams, James; Spangenthal, Selwyn

    2014-01-01

    Indacaterol 75 μg once daily is a long-acting β2 agonist approved for maintenance bronchodilator treatment in patients with chronic obstructive pulmonary disease (COPD). The purpose of this study was to evaluate patients' perception of onset of effect with a single dose. In this double-blind, crossover, Phase IV study, 40 patients were randomized to receive a single dose of indacaterol 75 μg or placebo via a dry powder inhaler device. The primary variable was time until patient's perception of onset of effect, using a simple self-administered (nonvalidated) questionnaire that patients answered at nine protocol-specified time points. Exploratory variables included change in forced expiratory volume in 1 second (FEV1) and change in percent predicted FEV1 from predose to postdose (determined 60-75 minutes postdose). The least-squares mean time to patient's perception of onset of effect was 25.4 minutes and 23.9 minutes for indacaterol and placebo, respectively. There was no significant effect for treatment, period, or sequence on the time to patient's perception. In addition, no statistically significant differences between treatments were observed for patient's global satisfaction with onset of effect and global expectation of treatment adherence. For the exploratory variable change in FEV1 from predose to postdose, indacaterol showed superiority over placebo with a clinically relevant least-squares mean treatment difference of 0.12 L (Pindacaterol 75 μg did not separate from placebo in terms of patient perception of onset, although there was an improvement in FEV1 for indacaterol compared with placebo. Development and use of a validated questionnaire may be needed to address the inconsistency in evaluating this patient-related outcome.

  17. Once-daily long-acting beta-agonists for chronic obstructive pulmonary disease: an indirect comparison of olodaterol and indacaterol.

    Science.gov (United States)

    Roskell, Neil S; Anzueto, Antonio; Hamilton, Alan; Disse, Bernd; Becker, Karin

    2014-01-01

    In the absence of head-to-head clinical trials comparing the once-daily, long-acting beta2-agonists olodaterol and indacaterol for the treatment of chronic obstructive pulmonary disease (COPD), an indirect treatment comparison by systematic review and synthesis of the available clinical evidence was conducted. A systematic literature review of randomized, controlled clinical trials in patients with COPD was performed to evaluate the efficacy and safety of olodaterol and indacaterol. Network meta-analysis and adjusted indirect comparison methods were employed to evaluate treatment efficacy, using outcomes based on trough forced expiratory volume in 1 second (FEV1), Transition Dyspnea Index, St George's Respiratory Questionnaire total score and response, rescue medication use, and proportion of patients with exacerbations. Eighteen trials were identified for meta-analysis (eight, olodaterol; ten, indacaterol). Olodaterol trials included patients of all severities, whilst indacaterol trials excluded patients with very severe COPD. Concomitant maintenance bronchodilator use was allowed in most olodaterol trials, but not in indacaterol trials. When similarly designed trials/data were analyzed for change from baseline in trough FEV1 (liters), the following mean differences (95% confidence interval) were observed: trials excluding concomitant bronchodilator: indacaterol 75 mcg versus olodaterol 5 mcg, -0.005 (-0.077 to 0.067), and indacaterol 150 mcg versus olodaterol 5 mcg, 0.020 (-0.036 to 0.077); trials with concomitant tiotropium: indacaterol 150 mcg versus olodaterol 5 mcg, 0.000 (-0.043 to 0.042). In sensitivity analyses of the full network, results for change from baseline in trough FEV1 favored indacaterol, but this dataset suffered from trial design heterogeneity. For the other endpoints investigated, no statistically significant differences were found when analyzed in the full network. When compared under similar trial conditions, olodaterol and indacaterol have

  18. Once-daily indacaterol 75 μg in moderate- to-severe COPD: results of a Phase IV study assessing time until patients’ perceived onset of effect

    Science.gov (United States)

    Siler, Thomas M; LaForce, Craig F; Kianifard, Farid; Williams, James; Spangenthal, Selwyn

    2014-01-01

    Background Indacaterol 75 μg once daily is a long-acting β2 agonist approved for maintenance bronchodilator treatment in patients with chronic obstructive pulmonary disease (COPD). The purpose of this study was to evaluate patients’ perception of onset of effect with a single dose. Methods In this double-blind, crossover, Phase IV study, 40 patients were randomized to receive a single dose of indacaterol 75 μg or placebo via a dry powder inhaler device. The primary variable was time until patient’s perception of onset of effect, using a simple self-administered (nonvalidated) questionnaire that patients answered at nine protocol-specified time points. Exploratory variables included change in forced expiratory volume in 1 second (FEV1) and change in percent predicted FEV1 from predose to postdose (determined 60–75 minutes postdose). Results The least-squares mean time to patient’s perception of onset of effect was 25.4 minutes and 23.9 minutes for indacaterol and placebo, respectively. There was no significant effect for treatment, period, or sequence on the time to patient’s perception. In addition, no statistically significant differences between treatments were observed for patient’s global satisfaction with onset of effect and global expectation of treatment adherence. For the exploratory variable change in FEV1 from predose to postdose, indacaterol showed superiority over placebo with a clinically relevant least-squares mean treatment difference of 0.12 L (Pindacaterol 75 μg did not separate from placebo in terms of patient perception of onset, although there was an improvement in FEV1 for indacaterol compared with placebo. Development and use of a validated questionnaire may be needed to address the inconsistency in evaluating this patient-related outcome. PMID:25214778

  19. Efficacy and safety of indacaterol 150 μg once-daily in COPD: a double-blind, randomised, 12-week study

    Directory of Open Access Journals (Sweden)

    Piggott Simon

    2010-03-01

    Full Text Available Abstract Background Indacaterol is a novel, once-daily (o.d. inhaled, long-acting β2-agonist in development for chronic obstructive pulmonary disease (COPD. This 12-week, double-blind study compared the efficacy, safety, and tolerability of indacaterol to that of placebo in patients with moderate-to-severe COPD. Methods Efficacy variables included 24-h trough FEV1 (mean of 23 h 10 min and 23 h 45 min post-dose at Week 12 (primary endpoint and after Day 1, and the percentage of COPD days with poor control (i.e., worsening symptoms. Safety was assessed by adverse events (AEs, mean serum potassium and blood glucose, QTc (Fridericia, and vital signs. Results Patients were randomised (n = 416, mean age 63 years to receive either indacaterol 150 μg o.d. (n = 211 or placebo (n = 205 via a single-dose dry-powder inhaler; 87.5% completed the study. Trough FEV1 (LSM ± SEM at Week 12 was 1.48 ± 0.018 L for indacaterol and 1.35 ± 0.019 L for placebo, a clinically relevant difference of 130 ± 24 mL (p 1 after one dose was significantly higher with indacaterol than placebo (p 1 than placebo, both on Day 1 and at Week 12, with indacaterol-placebo differences (LSM ± SEM of 190 ± 28 (p 1 (between 5 min and 4 h, 5 min and 1 h, and 1 and 4 h post-dose at Week 12 were all significantly greater with indacaterol than placebo (p 500 ms. Conclusions Indacaterol 150 μg o.d. provided clinically significant and sustained bronchodilation, reduced rescue medication use, and had a safety and tolerability profile similar to placebo. Trial registration NCT00624286

  20. Improving treatment satisfaction and other patient-reported outcomes in people with type 2 diabetes: the role of once-daily insulin glargine.

    Science.gov (United States)

    Bradley, C; Gilbride, C J B

    2008-07-01

    Insulin therapy becomes essential for many people with type 2 diabetes. After starting insulin, people with diabetes that is poorly controlled with oral agents typically report improved well-being and treatment satisfaction. However, healthcare professionals and people with type 2 diabetes are often reluctant to begin insulin treatment, citing concerns such as time/resources needed to educate patients, increased risks of hypoglycaemia and fear of injections, which lead them to focus on intensifying conventional oral therapy. Insulin glargine, which offers people with diabetes a once-a-day injection regimen with low risk of hypoglycaemia, is more likely to overcome such initial barriers than other more complex insulin regimens. Once-daily insulin glargine, in combination with modern glucose-dependent oral agents that do not need to be chased with food to prevent hypoglycaemia, does not require the fixed mealtimes and set amounts of carbohydrates necessary with twice-daily injection mixes and older sulphonylureas. We know that it is such dietary restrictions that cause the most damage to quality of life (QoL). To avoid damaging QoL unnecessarily and to ensure optimal satisfaction with treatment, it is important to evaluate the effects of treatment on QoL, treatment satisfaction and other patient-reported outcomes (PROs) using questionnaires validated for this purpose, such as the widely used Diabetes Treatment Satisfaction Questionnaire and the Audit of Diabetes-Dependent Quality of Life measure. A systematic electronic literature search identified reports of studies evaluating PROs associated with insulin glargine in comparison with other treatments. The studies show that insulin glargine is usually associated with greater improvements in treatment satisfaction and other PROs compared with intensifying oral therapy or alternative insulin regimens.

  1. Immunovirological Efficacy of Once-Daily Maraviroc Plus Ritonavir-Boosted Atazanavir After 48 Weeks in Naive HIV-Infected Patients.

    Science.gov (United States)

    Pulido, Ildefonso; Genebat, Miguel; Alvarez-Rios, Ana I; De Pablo-Bernal, Rebeca S; Rafii-El-Idrissi Benhnia, Mohammed; Pacheco, Yolanda M; Ruiz-Mateos, Ezequiel; Leal, Manuel

    2016-10-01

    Toxicities related to the use of nucleoside analogues have increased the interest in developing nucleoside-sparing regimens, mainly combining protease inhibitors with raltegravir. However, data regarding the use of CCR5-antagonists in this setting and in the naive scenario are scarce. The main objective was to analyze the immunovirological efficacy and tolerability of a low-dose, once-daily, maraviroc (MVC)-containing, nucleoside reverse transcriptase inhibitor-sparing dual therapy compared with standard triple therapy after 48 weeks for naive HIV-infected patients in the routine clinical practice setting. All naive HIV-infected patients with stable clinical condition that started antiretroviral treatment since February 1, 2008 to May 30,h 2012 were included. MVC clinical test was used to select candidate subjects to MVC therapy. Thirty-two subjects with MVC + atazanavir/ritonavir (ATV/r) and 66 with standard triple therapy were analyzed. A comparable virological efficacy between groups was found after 48 weeks (87.5% vs. 80.3% of HIV undetectability, p = 0.37, MVC + ATV/r and triple therapy groups, respectively). The CD4 recovery after 48 weeks was similar and more than 200 cells/mm(3) in both groups. No need of therapy changes or treatment discontinuations was observed in the MVC + ATV/r group. Effect on lipid profile, high-sensitivity C reactive protein, and β2-microglobulin was similar for both groups. Noteworthy, a significant increase of erythrocyte mean corpuscular volume was observed only in the triple therapy group. A nucleoside-sparing MVC-containing dual therapy showed similar immunovirological efficacy and tolerability than standard triple therapy in naive HIV-infected patients.

  2. Sustained effects of once-daily memantine treatment on cognition and functional communication skills in patients with moderate to severe Alzheimer's disease: results of a 16-week open-label trial.

    Science.gov (United States)

    Schulz, Jörg B; Rainer, Michael; Klünemann, Hans-Hermann; Kurz, Alexander; Wolf, Stefanie; Sternberg, Kati; Tennigkeit, Frank

    2011-01-01

    The present study evaluated the effects of once-daily memantine (20 mg) treatment on cognition and communication in patients with moderate to severe Alzheimer's disease (AD). In a multicenter, single-arm open-label study, outpatients diagnosed with AD (MMSE < 20; n = 97) were titrated from 5 mg to 20 mg once-daily memantine over 4 weeks. Once-daily memantine treatment (20 mg) was then continued for 8 weeks, followed by a 4-week wash-out period. The primary efficacy endpoint was the change from baseline in the Consortium to Establish a Registry for Alzheimer's Disease -Neuropsychological Battery (CERAD-NP) total score. Secondary efficacy endpoints included change from baseline in Functional Communication Language Inventory (FLCI) and ADCS-ADL19 total score, and the response from baseline in Clinical Global Impression of Change (CGI-C). The CERAD-NP total score improved significantly after 12 weeks of once-daily memantine treatment compared with baseline (5.9 ± 8.8; p < 0.0001). The FLCI total score improved significantly after 12 weeks compared with baseline (4.4 ± 6.8; p < 0.0001). These significant improvements were already observed after 4 and 8 weeks of once-daily memantine treatment and persisted after a 4-week wash-out period. ADCS-ADL19 total scores showed only slight increases from baseline, and CGI-C indicated that the majority of patients experienced an improvement or stabilization of the disease after 12 weeks. At least one Treatment-Emergent Adverse Event was reported by 38 (39.2%) patients. In patients with moderate to severe AD, once-daily memantine (20 mg) treatment significantly improved cognition and functional communication and was found to have a favorable safety and tolerability profile.

  3. Oral 5-Aminosalicylate, Mesalamine Suppository, and Mesalamine Enema as Initial Therapy for Ulcerative Proctitis in Clinical Practice with Quality of Care Implications

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    James M. Richter

    2016-01-01

    Full Text Available Background. Ulcerative proctitis (UP is typically treated initially with oral 5-aminosalicylate (“5-ASA”, mesalamine suppository, or mesalamine enema (“UP Rx”. Little is known about their effectiveness in practice. Methods. Using a US health insurance database, we identified new-onset UP patients between January 1, 2005, and December 31, 2007, based on the following: (1 initiation of UP Rx; (2 endoscopy in prior 30 days resulting in diagnosis of UP; and (3 no prior encounters for ulcerative colitis or Crohn’s disease. We examined the incidence of therapy escalation and total costs in relation to initial UP Rx. Results. We identified 548 patients: 327 received mesalamine suppository, 138 received oral 5-ASA, and 83 received mesalamine enema, as initial UP Rx. One-third receiving oral 5-ASA experienced therapy escalation over 12 months, 21% for both mesalamine suppository and enema. Mean cumulative total cost of UP Rx over 12 months was $1552, $996, and $986 for patients beginning therapy with oral 5-ASA, mesalamine enema, and mesalamine suppository, respectively. Contrary to expert recommendations the treatments were often not continued prophylactically. Conclusions. Treatment escalation was common, and total costs of therapy were higher, in patients who initiated treatment with oral 5-ASA. Further study is necessary to assess the significance of these observations.

  4. Oral 5-Aminosalicylate, Mesalamine Suppository, and Mesalamine Enema as Initial Therapy for Ulcerative Proctitis in Clinical Practice with Quality of Care Implications.

    Science.gov (United States)

    Richter, James M; Arshi, Nabeela K; Oster, Gerry

    2016-01-01

    Background. Ulcerative proctitis (UP) is typically treated initially with oral 5-aminosalicylate ("5-ASA"), mesalamine suppository, or mesalamine enema ("UP Rx"). Little is known about their effectiveness in practice. Methods. Using a US health insurance database, we identified new-onset UP patients between January 1, 2005, and December 31, 2007, based on the following: (1) initiation of UP Rx; (2) endoscopy in prior 30 days resulting in diagnosis of UP; and (3) no prior encounters for ulcerative colitis or Crohn's disease. We examined the incidence of therapy escalation and total costs in relation to initial UP Rx. Results. We identified 548 patients: 327 received mesalamine suppository, 138 received oral 5-ASA, and 83 received mesalamine enema, as initial UP Rx. One-third receiving oral 5-ASA experienced therapy escalation over 12 months, 21% for both mesalamine suppository and enema. Mean cumulative total cost of UP Rx over 12 months was $1552, $996, and $986 for patients beginning therapy with oral 5-ASA, mesalamine enema, and mesalamine suppository, respectively. Contrary to expert recommendations the treatments were often not continued prophylactically. Conclusions. Treatment escalation was common, and total costs of therapy were higher, in patients who initiated treatment with oral 5-ASA. Further study is necessary to assess the significance of these observations.

  5. Once-daily long-acting beta-agonists for chronic obstructive pulmonary disease: an indirect comparison of olodaterol and indacaterol

    Directory of Open Access Journals (Sweden)

    Roskell NS

    2014-07-01

    Full Text Available Neil S Roskell,1 Antonio Anzueto,2 Alan Hamilton,3 Bernd Disse,4 Karin Becker5 1Statistics, Bresmed Health Solutions Ltd, Sheffield, UK; 2School of Medicine, University of Texas Health Science Center, San Antonio, TX, USA; 3Medical Department, Boehringer Ingelheim (Canada Ltd, Burlington, ON, Canada; 4Medical Department, Boehringer Ingelheim GmbH, Ingelheim am Rhein, Germany; 5Global Health Economics and Outcomes Research, Boehringer Ingelheim GmbH, Ingelheim am Rhein, Germany Purpose: In the absence of head-to-head clinical trials comparing the once-daily, long-acting beta2-agonists olodaterol and indacaterol for the treatment of chronic obstructive pulmonary disease (COPD, an indirect treatment comparison by systematic review and synthesis of the available clinical evidence was conducted. Methods: A systematic literature review of randomized, controlled clinical trials in patients with COPD was performed to evaluate the efficacy and safety of olodaterol and indacaterol. Network meta-analysis and adjusted indirect comparison methods were employed to evaluate treatment efficacy, using outcomes based on trough forced expiratory volume in 1 second (FEV1, Transition Dyspnea Index, St George’s Respiratory Questionnaire total score and response, rescue medication use, and proportion of patients with exacerbations. Results: Eighteen trials were identified for meta-analysis (eight, olodaterol; ten, indacaterol. Olodaterol trials included patients of all severities, whilst indacaterol trials excluded patients with very severe COPD. Concomitant maintenance bronchodilator use was allowed in most olodaterol trials, but not in indacaterol trials. When similarly designed trials/data were analyzed for change from baseline in trough FEV1 (liters, the following mean differences (95% confidence interval were observed: trials excluding concomitant bronchodilator: indacaterol 75 mcg versus olodaterol 5 mcg, –0.005 (–0.077 to 0.067, and indacaterol 150 mcg

  6. The decrease in milk yield during once daily milking is due to regulation of synthetic activity rather than apoptosis of mammary epithelial cells in goats.

    Science.gov (United States)

    Ben Chedly, H; Lacasse, P; Marnet, P-G; Boutinaud, M

    2013-01-01

    Once daily milking (ODM) is a management practice that can improve working conditions and reduce production costs in dairy farming compared with twice daily milking (TDM). However, ODM is associated with a decrease in milk yield. Previous research indicated that disruption of tight junctions in the mammary gland may be one of the regulatory factors involved in the milk yield decrease observed during ODM. The aim of this study was to investigate the involvement of mammary epithelium disruption in the regulation of the activity and dynamics of mammary epithelial cells (MEC) during 5 weeks of ODM in goats. Twelve alpine goats (producing 3.67 ± 0.64 kg/day and 47 ± 1.6 days in milk) were assigned to two groups that were milked once or twice a day during 5 weeks and then switched back to TDM. Mammary biopsies were collected before and on days 2 and 16 of both ODM and TDM switchback periods. Milk purified epithelial cells were collected before and on days 1, 7, 21 and 28 during ODM as well on days 1 and 7 of the TDM switchback period. The mRNA levels of genes involved in the regulation of synthetic activity and apoptosis were analysed by RT-PCR in milk MEC and mammary biopsies. ODM decreased yields of milk (-23%), lactose (-23%) and casein (-16%). Lactose synthesis was regulated at the transcriptional level by downregulation of α-lactalbumin mRNA levels in both biopsy samples (-30%) and milk MEC (-74%). TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling) staining of mammary gland biopsies did not show any increase in cell apoptosis after 2 and 16 days of ODM (0.8% and 1%, respectively) despite upregulation of Bax mRNA levels in milk MEC. This suggests that the decrease in milk yield observed during ODM is attributable to a decrease in synthetic activity rather than to induction of MEC cell death. ODM induced the disruption of tight junctions in the mammary gland only on the first day of the treatment as indicated by increased blood

  7. Efficacy and safety of indacaterol 150 μg once-daily in COPD: a double-blind, randomised, 12-week study

    Science.gov (United States)

    2010-01-01

    Background Indacaterol is a novel, once-daily (o.d.) inhaled, long-acting β2-agonist in development for chronic obstructive pulmonary disease (COPD). This 12-week, double-blind study compared the efficacy, safety, and tolerability of indacaterol to that of placebo in patients with moderate-to-severe COPD. Methods Efficacy variables included 24-h trough FEV1 (mean of 23 h 10 min and 23 h 45 min post-dose) at Week 12 (primary endpoint) and after Day 1, and the percentage of COPD days with poor control (i.e., worsening symptoms). Safety was assessed by adverse events (AEs), mean serum potassium and blood glucose, QTc (Fridericia), and vital signs. Results Patients were randomised (n = 416, mean age 63 years) to receive either indacaterol 150 μg o.d. (n = 211) or placebo (n = 205) via a single-dose dry-powder inhaler; 87.5% completed the study. Trough FEV1 (LSM ± SEM) at Week 12 was 1.48 ± 0.018 L for indacaterol and 1.35 ± 0.019 L for placebo, a clinically relevant difference of 130 ± 24 mL (p indacaterol than placebo (p Indacaterol demonstrated significantly higher peak FEV1 than placebo, both on Day 1 and at Week 12, with indacaterol-placebo differences (LSM ± SEM) of 190 ± 28 (p indacaterol than placebo (p Indacaterol significantly reduced the percentage of days of poor control versus placebo by 22.5% (p indacaterol 49.3%, placebo 46.8%), with the most common AEs being COPD worsening (indacaterol 8.5%, placebo 12.2%) and cough (indacaterol 6.2%, placebo 7.3%). One patient died in the placebo group. Serum potassium and blood glucose levels did not differ significantly between the two groups, and no patient had QTc >500 ms. Conclusions Indacaterol 150 μg o.d. provided clinically significant and sustained bronchodilation, reduced rescue medication use, and had a safety and tolerability profile similar to placebo. Trial registration NCT00624286 PMID:20211002

  8. Once-daily indacaterol 75 µg in moderate- to-severe COPD: results of a Phase IV study assessing time until patients’ perceived onset of effect

    Directory of Open Access Journals (Sweden)

    Siler TM

    2014-09-01

    Full Text Available Thomas M Siler,1 Craig F LaForce,2 Farid Kianifard,3 James Williams,3 Selwyn Spangenthal4 1Midwest Chest Consultants, St Charles, MO, USA; 2North Carolina Clinical Research, Raleigh, NC, USA; 3Novartis Pharmaceuticals, East Hanover, NJ, USA; 4Charlotte Lung and Health Center, Charlotte, NC, USA Background: Indacaterol 75 µg once daily is a long-acting β2 agonist approved for maintenance bronchodilator treatment in patients with chronic obstructive pulmonary disease (COPD. The purpose of this study was to evaluate patients' perception of onset of effect with a single dose. Methods: In this double-blind, crossover, Phase IV study, 40 patients were randomized to receive a single dose of indacaterol 75 µg or placebo via a dry powder inhaler device. The primary variable was time until patient’s perception of onset of effect, using a simple self-administered (nonvalidated questionnaire that patients answered at nine protocol-specified time points. Exploratory variables included change in forced expiratory volume in 1 second (FEV1 and change in percent predicted FEV1 from predose to postdose (determined 60–75 minutes postdose. Results: The least-squares mean time to patient’s perception of onset of effect was 25.4 minutes and 23.9 minutes for indacaterol and placebo, respectively. There was no significant effect for treatment, period, or sequence on the time to patient's perception. In addition, no statistically significant differences between treatments were observed for patient's global satisfaction with onset of effect and global expectation of treatment adherence. For the exploratory variable change in FEV1 from predose to postdose, indacaterol showed superiority over placebo with a clinically relevant least-squares mean treatment difference of 0.12 L (P<0.0001. There was little or no association between patient’s perception of time to onset of effect and change in FEV1, or change in percent predicted FEV1. Both treatments were well

  9. A UK-based cost-utility analysis of indacaterol, a once-daily maintenance bronchodilator for patients with COPD, using real world evidence on resource use.

    Science.gov (United States)

    Price, David; Asukai, Yumi; Ananthapavan, Jaithri; Malcolm, Bill; Radwan, Amr; Keyzor, Ian

    2013-06-01

    Chronic Obstructive Pulmonary Disease (COPD) is a chronic, progressive disease that is not curable. However, there are effective treatments available. In the UK, long-acting bronchodilators are first-line treatments for COPD patients requiring maintenance therapy, and there are several options available. The aim of this study is to establish, from the UK National Health Service (NHS) perspective, the cost-effectiveness profile of indacaterol, the first once-daily long-acting beta2-agonist (LABA), compared with tiotropium and salmeterol, in patients with moderate to severe COPD. In assessing the cost-effectiveness of COPD therapies, this study has the advantage of using real world evidence on the resource use associated with COPD management across the spectrum of the disease. A Markov model was developed with four health states following the GOLD classification for severity of airflow limitation. The model time horizon was 3 years, and the cycle length was 3 months. From each state, patients could experience a severe or non-severe exacerbation, move to a different COPD state, remain in the current state or die. Transition probabilities were based on data from the indacaterol clinical trials. The majority of the resource use data was taken from the Optimum Patient Care Research Database (OPCRD), which contains data from over 20,000 COPD patients in England and Scotland. Cost data were taken from UK-based sources and published literature and presented for the cost year 2011. Health-related quality of life was the main outcome of interest and utility data for the COPD states were based on data from the indacaterol clinical trials and disutility due to exacerbations were taken from the literature. Both one way and probabilistic sensitivity analyses were performed to test the robustness of the results. Indacaterol dominated in the comparison with salmeterol producing an incremental QALY gain of 0.008 and cost savings of £110 per patient over a 3-year time horizon. In

  10. Prediction of efficacy for conversion from adjunctive therapy to monotherapy with eslicarbazepine acetate 800 mg once daily for partial-onset epilepsy

    Science.gov (United States)

    Sunkaraneni, Soujanya; Passarell, Julie A; Ludwig, Elizabeth A; Fiedler-Kelly, Jill; Pitner, Janet K; Grinnell, Todd A; Blum, David

    2017-01-01

    Purpose Eslicarbazepine acetate (ESL) is a once-daily (QD) oral antiepileptic drug (AED) indicated for partial-onset seizures (POS). Clinical studies of gradual conversion to ESL 1,200 and 1,600 mg QD monotherapies were previously conducted in patients with POS who were not well-controlled by 1 or 2 AEDs. This report describes modeling and simulation of plasma eslicarbazepine (primary active metabolite of ESL) concentrations and time to monotherapy study exit to predict efficacy for conversion to ESL monotherapy at a lower dose of 800 mg, as an option for patients requiring or not tolerating higher doses since this regimen is effective in adjunctive therapy for POS. Patients and methods A previously developed population pharmacokinetic model for ESL monotherapy was used to predict minimum plasma eslicarbazepine concentration (Cmin) in 1,500 virtual patients taking 1 (n=1,000) or 2 (n=500) AEDs at baseline, treated with ESL 400 mg QD for 1 week, followed by 800 mg QD for 17 weeks (similar to ESL monotherapy trials where the other AEDs were withdrawn during the first 6 weeks following titration to the randomized ESL dose). Model-predicted Cmin as a time-varying covariate and number of baseline AEDs were used to determine the weekly probability of each patient meeting exit criteria (65.3% threshold) indicative of worsening seizure control in 500 simulated ESL monotherapy trials. A previously developed extended Cox proportional hazards exposure–response model was used to relate time-varying eslicarbazepine exposure to the time to study exit. Results For virtual patients receiving ESL monotherapy (800 mg QD), the 95% upper prediction limit for exit rate at 112 days of 34.9% in patients taking 1 AED at baseline was well below the 65.3% threshold from historical control trials, while the estimate for patients taking 2 AEDs (70.6%) was slightly above the historical control threshold. Conclusion This model-based assessment supports conversion to ESL 800 mg QD monotherapy

  11. Real-world glycemic outcomes in patients with type 2 diabetes initiating exenatide once weekly and liraglutide once daily: a retrospective cohort study

    Directory of Open Access Journals (Sweden)

    Saunders WB

    2016-07-01

    Full Text Available William B Saunders,1 Hiep Nguyen,2 Iftekhar Kalsekar2 1Department of Public Health Sciences, College of Health and Human Services, The University of North Carolina at Charlotte, Charlotte, NC, 2AstraZeneca, Fort Washington, PA, USA Aim: The glucagon-like peptide-1 receptor agonists exenatide once weekly (QW and liraglutide once daily (QD have demonstrated improvements in glycemic outcomes in patients with type 2 diabetes mellitus in randomized clinical trials. However, little is known about their real-world comparative effectiveness. This retrospective cohort study used the Quintiles Electronic Medical Record database to evaluate the 6-month change in glycated hemoglobin (A1C for patients initiating exenatide QW or liraglutide QD.Methods: Patients with type 2 diabetes mellitus prescribed exenatide QW (n=664 or liraglutide QD (n=3,283 between February 1, 2012 and May 31, 2013 were identified. Baseline A1C measures were from 75 days before to 15 days after initiating exenatide QW or liraglutide QD, with follow-up measures documented at 6 months (±45 days. Adjusted linear regression models compared the difference in mean A1C change. A priori defined sensitivity analysis was performed in the subgroup of patients with baseline A1C ≥7.0% and no prescription for insulin during the 12-month pre-index period.Results: For exenatide QW and liraglutide QD, respectively, mean (SD age of the main study cohort was 58.01 (10.97 and 58.12 (11.05 years, mean (SD baseline A1C was 8.4% (1.6 and 8.4% (1.6, and 48.2% and 54.2% of patients were women. In adjusted models, change in A1C did not differ between exenatide QW and liraglutide QD during 6 months of follow-up. Results were consistent in the subgroup analyses.Conclusion: In a real-world setting, A1C similarly improves in patients initiating exenatide QW or liraglutide QD. Keywords: diabetes, exenatide, outcomes

  12. Indacaterol, a once-daily beta2-agonist, versus twice-daily beta₂-agonists or placebo for chronic obstructive pulmonary disease.

    Science.gov (United States)

    Geake, James B; Dabscheck, Eli J; Wood-Baker, Richard; Cates, Christopher J

    2015-01-10

    Indacaterol is an inhaled long-acting beta2-agonist that is administered once daily and has been investigated as a treatment for chronic obstructive pulmonary disease (COPD). Four different doses have been investigated (75 mcg, 150 mcg, 300 mcg and 600 mcg). The relative effects of different doses of once-daily indacaterol in the management of patients with COPD are uncertain. To compare the efficacy and safety of indacaterol versus placebo and alternative twice-daily long-acting beta2-agonists for the treatment of patients with stable COPD. We identified trials from the Cochrane Airways Group Specialised Register of trials (CAGR), handsearched respiratory journals and meeting abstracts and searched the Novartis trials registry and ClinicalTrials.gov. The date of the most recent search was 8 November 2014. We included all randomised controlled trials comparing indacaterol at any dose versus placebo or alternative long-acting beta2-agonists. Trials were required to be of at least 12 weeks' duration and had to include adults older than 18 years with a confirmed spirometric diagnosis of COPD. Two review authors (JBG, EJD) independently assessed for possible inclusion all citations identified as a result of the search. Disagreements were resolved through discussion or, if required, through resolution by a third review author (RWB). One review author (JBG) extracted data from trials identified by the search and entered these data into Review Manager 5.1 for statistical analysis. Data entry was cross-checked by a second review author (EJD, CJC). A total of 13 trials with 9961 participants were included in the review. Ten trials with a total of 8562 participants involved an indacaterol versus placebo comparison. Five trials with a total of 4133 participants involved an indacaterol versus twice-daily beta2-agonist comparison. The comparator beta2-agonists were salmeterol, formoterol and eformoterol. One of these trials, with a total of 90 participants, provided no data

  13. Effects of Tadalafil Once-Daily or On-Demand vs Placebo on Return to Baseline Erectile Function After Bilateral Nerve-Sparing Radical Prostatectomy - Results from a Randomized Controlled Trial (REACTT)

    DEFF Research Database (Denmark)

    Mulhall, John P; Brock, Gerald; Oelke, Matthias;

    2016-01-01

    INTRODUCTION AND AIM: The multicenter, randomized, double-blind, double-dummy, placebo-controlled REACTT trial suggested that treatment with tadalafil once daily (OaD) started early after bilateral nerve-sparing radical prostatectomy (nsRP) for prostate cancer may contribute to erectile function ...

  14. Once-daily basal insulin glargine versus thrice-daily prandial insulin lispro in people with type 2 diabetes on oral hypoglycaemic agents (APOLLO): an open randomised controlled trial

    DEFF Research Database (Denmark)

    Bretzel, R.G.; Nuber, U.; Landgraf, W.

    2008-01-01

    BACKGROUND: As type 2 diabetes mellitus progresses, oral hypoglycaemic agents often fail to maintain blood glucose control and insulin is needed. We investigated whether the addition of once-daily insulin glargine is non-inferior to three-times daily prandial insulin lispro in overall glycaemic c...

  15. Comparison of efficacies of once-daily dose multimatrix mesalazine and multiple-dose mesalazine for the maintenance of remission in ulcerative colitis: a randomized, double-blind study.

    Science.gov (United States)

    Ogata, Haruhiko; Ohori, Akihiro; Nishino, Haruo; Mizushima, Seiichi; Hagino, Atsushi; Hibi, Toshifumi

    2017-07-01

    This study compared the efficacy of once-daily administration of multimatrix mesalazine 2.4 g/day with multiple-dose mesalazine for the maintenance of remission. In this multicenter, randomized, double-blind study, 203 patients with ulcerative colitis in remission received multimatrix mesalazine 2.4 g/day once-daily or time-dependent (controlled-release) mesalazine 2.25 g/day 3 times-daily for 48 weeks. The primary efficacy endpoint was the proportion of patients without rectal bleeding. The proportion of patients without rectal bleeding during the 48-week treatment period in the per protocol set was 84.8% (84/99) in the multimatrix mesalazine 2.4 g/day group and 78.0% (78/100) in the controlled-release mesalazine 2.25 g/day group. The difference between the 2 treatment groups was 6.8% (two-sided 95% confidence interval, -3.9% to 17.6%). The noninferiority margin of -10% was met in the comparison of multimatrix mesalazine 2.4 g/day once-daily with controlled-release mesalazine 2.25 g/day. Multimatrix mesalazine 2.4 g/day once-daily demonstrated consistent efficacy in all subgroups. There was no difference between the 2 treatment groups with regard to safety. A once-daily dose of 2 multimatrix mesalazine tablets (2.4 g) was not inferior to controlled-release mesalazine 2.25 g/day 3 times-daily in maintaining absence of rectal bleeding in ulcerative colitis.

  16. Efficacy of once-daily indacaterol 75 μg relative to alternative bronchodilators in COPD: A study level and a patient level network meta-analysis

    Science.gov (United States)

    2012-01-01

    Background The objective of this study was to evaluate the comparative efficacy of indacaterol 75 μg once daily (OD), tiotropium 18 μg OD, salmeterol 50 μg twice daily (BID), formoterol 12 μg BID, and placebo for the treatment of chronic obstructive pulmonary disease (COPD) based on individual patient data (IPD) from randomized controlled trials (RCTs) from the indacaterol trial program and aggregate data (AD) identified from a systematic review of RCTs. Methods 22 RCTs were included in the AD analysis that evaluated: indacaterol 75 μg (n = 2 studies), indacaterol 150 μg n = 5 (i.e. salmeterol 50 μg) (n = 5), indacaterol 300 μg (n = 2), tiotropium 18 μg (n = 10), salmeterol 50 μg (n = 7), and formoterol 12 μg (n = 4). All of the studies except for one head-to-head comparison (tiotropium vs. salmeterol) were placebo controlled. Outcomes of interest were trough forced expiratory volume in 1 second (FEV1) and St. George’s Respiratory Questionnaire (SGRQ) total score at week 12. The AD from all trials was analysed simultaneously using a Bayesian network meta-analysis (NMA) and relative treatment effects between all regimens were obtained. In a separate analysis, the IPD available from the 6 indacaterol RCTs was analysed in a NMA. Treatment-by-covariate interactions were included in both analyses to improve similarity of the trials. Results All interventions compared were more efficacious than placebo regarding FEV1 at 12 weeks. Indacaterol 75 μg is expected to result in a comparable FEV1 at 12 weeks to tiotropium and salmeterol based on both IPD and AD analyses. In comparison to formoterol, the IPD and AD results indicate indacaterol 75 μg is more efficacious (IPD = 0.07 L difference; 95%Credible Interval (CrI) 0.02 to 0.11; AD = 0.05 L difference; 95%CrI 0.01; 0.09). In terms of SGRQ total score at 12 weeks, indacaterol 75 μg and formoterol were more efficacious than placebo

  17. Efficacy of once-daily indacaterol 75 μg relative to alternative bronchodilators in COPD: a study level and a patient level network meta-analysis.

    Science.gov (United States)

    Cope, Shannon; Zhang, Jie; Williams, James; Jansen, Jeroen P

    2012-06-25

    The objective of this study was to evaluate the comparative efficacy of indacaterol 75 μg once daily (OD), tiotropium 18 μg OD, salmeterol 50 μg twice daily (BID), formoterol 12 μg BID, and placebo for the treatment of chronic obstructive pulmonary disease (COPD) based on individual patient data (IPD) from randomized controlled trials (RCTs) from the indacaterol trial program and aggregate data (AD) identified from a systematic review of RCTs. 22 RCTs were included in the AD analysis that evaluated: indacaterol 75 μg (n = 2 studies), indacaterol 150 μg n = 5 (i.e. salmeterol 50 μg) (n = 5), indacaterol 300 μg (n = 2), tiotropium 18 μg (n = 10), salmeterol 50 μg (n = 7), and formoterol 12 μg (n = 4). All of the studies except for one head-to-head comparison (tiotropium vs. salmeterol) were placebo controlled. Outcomes of interest were trough forced expiratory volume in 1 second (FEV1) and St. George's Respiratory Questionnaire (SGRQ) total score at week 12. The AD from all trials was analysed simultaneously using a Bayesian network meta-analysis (NMA) and relative treatment effects between all regimens were obtained. In a separate analysis, the IPD available from the 6 indacaterol RCTs was analysed in a NMA. Treatment-by-covariate interactions were included in both analyses to improve similarity of the trials. All interventions compared were more efficacious than placebo regarding FEV1 at 12 weeks. Indacaterol 75 μg is expected to result in a comparable FEV1 at 12 weeks to tiotropium and salmeterol based on both IPD and AD analyses. In comparison to formoterol, the IPD and AD results indicate indacaterol 75 μg is more efficacious (IPD = 0.07 L difference; 95%Credible Interval (CrI) 0.02 to 0.11; AD = 0.05 L difference; 95%CrI 0.01; 0.09). In terms of SGRQ total score at 12 weeks, indacaterol 75 μg and formoterol were more efficacious than placebo, whereas for tiotropium and salmeterol the credible intervals included zero for the AD results only

  18. Efficacy of once-daily indacaterol 75 μg relative to alternative bronchodilators in COPD: A study level and a patient level network meta-analysis

    Directory of Open Access Journals (Sweden)

    Cope Shannon

    2012-06-01

    Full Text Available Abstract Background The objective of this study was to evaluate the comparative efficacy of indacaterol 75 μg once daily (OD, tiotropium 18 μg OD, salmeterol 50 μg twice daily (BID, formoterol 12 μg BID, and placebo for the treatment of chronic obstructive pulmonary disease (COPD based on individual patient data (IPD from randomized controlled trials (RCTs from the indacaterol trial program and aggregate data (AD identified from a systematic review of RCTs. Methods 22 RCTs were included in the AD analysis that evaluated: indacaterol 75 μg (n = 2 studies, indacaterol 150 μg n = 5 (i.e. salmeterol 50 μg (n = 5, indacaterol 300 μg (n = 2, tiotropium 18 μg (n = 10, salmeterol 50 μg (n = 7, and formoterol 12 μg (n = 4. All of the studies except for one head-to-head comparison (tiotropium vs. salmeterol were placebo controlled. Outcomes of interest were trough forced expiratory volume in 1 second (FEV1 and St. George’s Respiratory Questionnaire (SGRQ total score at week 12. The AD from all trials was analysed simultaneously using a Bayesian network meta-analysis (NMA and relative treatment effects between all regimens were obtained. In a separate analysis, the IPD available from the 6 indacaterol RCTs was analysed in a NMA. Treatment-by-covariate interactions were included in both analyses to improve similarity of the trials. Results All interventions compared were more efficacious than placebo regarding FEV1 at 12 weeks. Indacaterol 75 μg is expected to result in a comparable FEV1 at 12 weeks to tiotropium and salmeterol based on both IPD and AD analyses. In comparison to formoterol, the IPD and AD results indicate indacaterol 75 μg is more efficacious (IPD = 0.07 L difference; 95%Credible Interval (CrI 0.02 to 0.11; AD = 0.05 L difference; 95%CrI 0.01; 0.09. In terms of SGRQ total score at 12 weeks, indacaterol 75 μg and formoterol were more efficacious than

  19. Once-daily indacaterol versus tiotropium for patients with severe chronic obstructive pulmonary disease (INVIGORATE): a randomised, blinded, parallel-group study.

    Science.gov (United States)

    Decramer, Marc L; Chapman, Kenneth R; Dahl, Ronald; Frith, Peter; Devouassoux, Gilles; Fritscher, Carlos; Cameron, Ray; Shoaib, Muhammad; Lawrence, David; Young, David; McBryan, Danny

    2013-09-01

    We compared the efficacy and safety of indacaterol and tiotropium in patients with severe chronic obstructive pulmonary disease (COPD) and a history of at least one moderate to severe exacerbation in the previous 12 months. In this multicentre, randomised, blinded, double-dummy, parallel group study, we enrolled patients aged 40 years or older with severe COPD and at least one exacerbation within the previous year. We used a computer-generated sequence to randomly allocate patients (1:1; stratified by baseline inhaled corticosteroid use, with the balance of treatments maintained at country level) to receive either indacaterol (150 μg) or tiotropium (18 μg) once-daily for 52 weeks. Our primary and key secondary objectives were to investigate whether indacaterol was non-inferior to tiotropium for trough forced expiratory volume in 1 s (FEV1) at week 12 (primary endpoint), and for rate of exacerbations at week 52 (secondary endpoint). Analysis populations for the primary and key secondary endpoints were per-protocol sets. The safety set included all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT00845728. Between March 16, 2009, and July 5, 2012, we enrolled and randomly allocated 3444 patients: 1723 to indacaterol and 1721 to tiotropium. At week 12, the estimated least squares mean trough FEV1 difference between the groups was -0.011 L (least squares mean with indacaterol [n=1450] 1.134 L [SE 0.008] vs tiotropium [n=1467] 1.145 L [0.008]; one-sided 97.5% CI lower limit -0.026 L; pindacaterol was non-inferior to tiotropium. Indacaterol did not show non-inferiority in terms of annualised exacerbation rates: 0.79 (indacaterol, n=1529) versus 0.61 (tiotropium, n=1543); ratio 1.29 (one-sided 97.5% CI upper limit 1.44). In the safety set, we recorded no between-group difference in the number of patients who had adverse events (indacaterol 1119 [65%] of 1721 patients vs tiotropium 1065 [62%] of 1718

  20. Efficacy and safety of once-daily inhaled umeclidinium/vilanterol in Asian patients with COPD: results from a randomized, placebo-controlled study

    Science.gov (United States)

    Zheng, Jinping; Zhong, Nanshan; Newlands, Amy; Church, Alison; Goh, Aik H

    2015-01-01

    Background Combination of the inhaled long-acting muscarinic antagonist umeclidinium (UMEC; GSK573719) with the long-acting β2-agonist vilanterol (VI) is an approved maintenance treatment for COPD in the US and EU. We compared the efficacy and safety of UMEC/VI with placebo in patients with COPD of Asian ancestry. Patients and methods In this 24-week, Phase III, multicenter, randomized, double-blind, placebo-controlled, parallel-group study, patients were randomized 1:1:1 to UMEC/VI 125/25 μg, UMEC/VI 62.5/25 μg, or placebo. The primary efficacy end point was trough forced expiratory volume in 1 second (FEV1) on day 169; secondary end points were Transition Dyspnea Index (TDI) focal score at week 24 and weighted mean (WM) FEV1 over 0–6 hours postdose on day 1. Additional end points and safety were also assessed. Results Both UMEC/VI 125/25 μg and UMEC/VI 62.5/25 μg statistically significantly improved trough FEV1 at day 169 versus placebo (UMEC/VI 125/25 μg, 0.216 L, [95% confidence interval [CI] 0.175–0.257]; UMEC/VI 62.5/25 μg, 0.151 L, 95% CI 0.110–0.191; both P<0.001). Statistically significant improvements in TDI score were observed for both UMEC/VI groups versus placebo (UMEC/VI 125/25 μg, 0.9, 95% CI 0.3–1.4, P=0.002; UMEC/VI 62.5/25 μg, 0.7, 95% CI 0.1–1.2, P=0.016). On day 1, both UMEC/VI groups improved 0–6-hour WM FEV1 versus placebo (UMEC/VI 125/25 μg, 0.182 L 95% CI 0.161–0.203; UMEC/VI 62.5/25 μg, 0.160 L, 95% CI 0.139–0.181; both P<0.001). Statistically significant improvements for UMEC/VI groups versus placebo were observed for rescue albuterol use at weeks 1–24 (puffs/day, both P<0.001). The incidence of adverse events was similar across groups. Conclusion In Asian patients with COPD, once-daily UMEC/VI 125/25 μg and UMEC 62.5/25 μg resulted in clinically meaningful and statistically significant improvements in lung-function end points versus placebo. Symptomatic and quality of life measures also improved. The safety

  1. Prediction of efficacy for conversion from adjunctive therapy to monotherapy with eslicarbazepine acetate 800 mg once daily for partial-onset epilepsy

    Directory of Open Access Journals (Sweden)

    Sunkaraneni S

    2017-06-01

    Full Text Available Soujanya Sunkaraneni,1 Julie A Passarell,2 Elizabeth A Ludwig,2 Jill Fiedler-Kelly,2 Janet K Pitner,1 Todd A Grinnell,1 David Blum1 1Sunovion Pharmaceuticals Inc., Marlborough, MA, USA; 2Cognigen Corporation (a SimulationsPlus company, Buffalo, NY, USA Purpose: Eslicarbazepine acetate (ESL is a once-daily (QD oral antiepileptic drug (AED indicated for partial-onset seizures (POS. Clinical studies of gradual conversion to ESL 1,200 and 1,600 mg QD monotherapies were previously conducted in patients with POS who were not well-controlled by 1 or 2 AEDs. This report describes modeling and simulation of plasma eslicarbazepine (primary active metabolite of ESL concentrations and time to monotherapy study exit to predict efficacy for conversion to ESL monotherapy at a lower dose of 800 mg, as an option for patients requiring or not tolerating higher doses since this regimen is effective in adjunctive therapy for POS. Patients and methods: A previously developed population pharmacokinetic model for ESL monotherapy was used to predict minimum plasma eslicarbazepine concentration (Cmin in 1,500 virtual patients taking 1 (n=1,000 or 2 (n=500 AEDs at baseline, treated with ESL 400 mg QD for 1 week, followed by 800 mg QD for 17 weeks (similar to ESL monotherapy trials where the other AEDs were withdrawn during the first 6 weeks following titration to the randomized ESL dose. Model-predicted Cmin as a time-varying covariate and number of baseline AEDs were used to determine the weekly probability of each patient meeting exit criteria (65.3% threshold indicative of worsening seizure control in 500 simulated ESL monotherapy trials. A previously developed extended Cox proportional hazards exposure–response model was used to relate time-varying eslicarbazepine exposure to the time to study exit. Results: For virtual patients receiving ESL monotherapy (800 mg QD, the 95% upper prediction limit for exit rate at 112 days of 34.9% in patients taking 1

  2. Expression of key lipid metabolism genes in adipose tissue is not altered by once-daily milking during a feed restriction of grazing dairy cows.

    Science.gov (United States)

    Grala, T M; Roche, J R; Phyn, C V C; Rius, A G; Boyle, R H; Snell, R G; Kay, J K

    2013-01-01

    The objective of this study was to investigate the effect of reduced milking frequency, at 2 feeding levels, on gene expression in adipose tissue of grazing dairy cows during early lactation. Multiparous Holstein-Friesian and Holstein-Friesian × Jersey cows (n=120) were grazed on pasture and milked twice daily (2×) from calving to 34±6d in milk (mean ± standard deviation). Cows were then allocated to 1 of 4 treatments in a 2×2 factorial arrangement. Treatments consisted of 2 milking frequencies (2× or once daily; 1×) and 2 feeding levels for 3 wk: adequately fed (AF), consuming 14.3 kg of dry matter/cow per day, or underfed (UF), consuming 8.3 kg of dry matter/cow per day. After the treatment period, all cows were fed to target grazing residuals ≥1,600 kg of DM/cow per day and milked 2× for 20 wk. Adipose tissue was collected from 12 cows per treatment by subcutaneous biopsy at -1, 3, and 5 wk relative to treatment start, RNA was extracted, and transcript abundance of genes involved in lipid metabolism was quantified using a linear mixed model. At the end of the 3-wk treatment period, transcript abundance of genes involved in fatty acid (FA) uptake into adipose tissue (LPL), FA synthesis [FA synthase (FASN) and stearoyl-coenzyme A desaturase (SCD)], FA oxidation [acyl-coenzyme A synthetase long-chain family member 1 (ACSL1) and carnitine palmitoyltransferase 2 (CPT2)], glyceroneogenesis [glycerol-3-phosphate dehydrogenase 1 (GPD1) and pyruvate carboxylase (PC)], and triacylglyceride synthesis [diacylglycerol O-acyltransferase 2 (DGAT2)] were greater in AF1× cows compared with all other treatments. However, when cows were underfed, no effects of milking frequency were observed on transcript abundance of genes involved in adipose lipid metabolism. Despite increases in plasma NEFA concentrations in UF cows, no effects of underfeeding were observed on the transcription of lipolytic genes. At 5 wk, after cows were returned to 2× milking and standard feed

  3. Effectiveness and gastrointestinal tolerability during conversion and titration with once-daily OROS® hydromorphone extended release in opioid-tolerant patients with chronic low back pain

    Directory of Open Access Journals (Sweden)

    Hale ME

    2013-05-01

    Full Text Available Martin E Hale,1 Srinivas R Nalamachu,2 Arif Khan,3 Michael Kutch4,* 1Gold Coast Research, LLC, Weston, FL, USA; 2International Clinical Research Institute, Overland Park, KS, USA; 3MedNorthwest Clinical Research Center, Bellevue, WA, USA; Duke University Medical Center, Durham, NC, USA; 4Applied Clinical Intelligence, LLC, Bala Cynwyd, PA, USA *Affiliation at the time this work was completed. Michael Kutch is currently affiliated with Cytel Inc, Chesterbrook, PA, USA Purpose: To describe the efficacy and safety of hydromorphone extended-release tablets (OROS hydromorphone ER during dose conversion and titration. Patients and methods: A total of 459 opioid-tolerant adults with chronic moderate to severe low back pain participated in an open-label, 2- to 4-week conversion/titration phase of a double-blind, placebo-controlled, randomized withdrawal trial, conducted at 70 centers in the United States. Patients were converted to once-daily OROS hydromorphone ER at 75% of the equianalgesic dose of their prior total daily opioid dose (5:1 conversion ratio, and titrated as frequently as every 3 days to a maximum dose of 64 mg/day. The primary outcome measure was change in pain intensity numeric rating scale; additional assessments included the Patient Global Assessment and the Roland–Morris Disability Questionnaire scores. Safety assessments were performed at each visit and consisted of recording and monitoring all adverse events (AEs and serious AEs. Results: Mean (standard deviation final daily dose of OROS hydromorphone ER was 37.5 (17.8 mg. Mean (standard error of the mean [SEM] numeric rating scale scores decreased from 6.6 (0.1 at screening to 4.3 (0.1 at the final titration visit (mean [SEM] change, -2.3 [0.1], representing a 34.8% reduction. Mean (SEM change in Patient Global Assessment was -0.6 (0.1, and mean change (SEM in the Roland–Morris Disability Questionnaire was -2.8 (0.3. Patients achieving a stable dose showed greater improvement

  4. Efficacy and tolerability of indacaterol 75 μg once daily in patients aged ≥40 years with chronic obstructive pulmonary disease: results from 2 double-blind, placebo-controlled 12-week studies.

    Science.gov (United States)

    Kerwin, Edward M; Gotfried, Mark H; Lawrence, David; Lassen, Cheryl; Kramer, Benjamin

    2011-12-01

    Indacaterol is the first once-daily, long-acting, inhaled β(2)-agonist bronchodilator for maintenance treatment of chronic obstructive pulmonary disease (COPD). Two studies (previously reported in a Congress abstract) were performed in 2010 to provide efficacy and tolerability data to support the application for approval in the United States of indacaterol 75 μg once daily, a dose lower than that previously investigated in most studies. The primary objective was to evaluate the efficacy of indacaterol 75 μg once daily in terms of 24-hour post-dose ("trough") forced expiratory volume in the first second of respiration (FEV(1)) compared with placebo after 12 weeks of treatment. Patients with moderate to severe COPD were randomized to receive double-blind treatment with indacaterol 75 μg once daily (n = 163 and 159) or placebo (n = 160 and 159) for 12 weeks. In addition to trough FEV(1) after 12 weeks, rescue albuterol use, health status (St. George's Respiratory Questionnaire [SGRQ]), and tolerability were evaluated. Clinically relevant differences between active and placebo treatments were defined as ≥120 mL for trough FEV(1) and a decrease of ≥4 units in SGRQ total score. Of patients enrolled in the 2 studies, 54% were men, and 90% and 94% were white, with mean age 64 and 61 years. Mean duration of COPD was 7 years; smoking history was 52 pack-years; and 45% and 37% of patients were receiving inhaled corticosteroid therapy. At week 12, indacaterol demonstrated clinically relevant bronchodilator efficacy, increasing trough FEV(1) by ≥120 mL versus placebo (P indacaterol therapy, rescue albuterol use was reduced by 1.2 and 0.7 puffs per day (P indacaterol group versus the placebo group by -3.8 and -3.6, respectively (P ≤ 0.01). Adverse events were reported for 49% and 45% of patients receiving indacaterol therapy, and for 46% and 41% receiving placebo. Compared with placebo, indacaterol 75 μg once daily provided statistically significant and clinically

  5. MMX-I: data-processing software for multimodal X-ray imaging and tomography

    Energy Technology Data Exchange (ETDEWEB)

    Bergamaschi, Antoine, E-mail: antoine.bergamaschi@synchrotron-soleil.fr; Medjoubi, Kadda [Synchrotron SOLEIL, BP 48, Saint-Aubin, 91192 Gif sur Yvette (France); Messaoudi, Cédric; Marco, Sergio [Université Paris-Saclay, CNRS, Université Paris-Saclay, F-91405 Orsay (France); Institut Curie, INSERM, PSL Reseach University, F-91405 Orsay (France); Somogyi, Andrea [Synchrotron SOLEIL, BP 48, Saint-Aubin, 91192 Gif sur Yvette (France)

    2016-04-12

    The MMX-I open-source software has been developed for processing and reconstruction of large multimodal X-ray imaging and tomography datasets. The recent version of MMX-I is optimized for scanning X-ray fluorescence, phase-, absorption- and dark-field contrast techniques. This, together with its implementation in Java, makes MMX-I a versatile and friendly user tool for X-ray imaging. A new multi-platform freeware has been developed for the processing and reconstruction of scanning multi-technique X-ray imaging and tomography datasets. The software platform aims to treat different scanning imaging techniques: X-ray fluorescence, phase, absorption and dark field and any of their combinations, thus providing an easy-to-use data processing tool for the X-ray imaging user community. A dedicated data input stream copes with the input and management of large datasets (several hundred GB) collected during a typical multi-technique fast scan at the Nanoscopium beamline and even on a standard PC. To the authors’ knowledge, this is the first software tool that aims at treating all of the modalities of scanning multi-technique imaging and tomography experiments.

  6. DRV concentrations and viral load in CSF in patients on DRV/r 600/100 or 800/100mg once daily plus two NRTI

    Directory of Open Access Journals (Sweden)

    Silvana Di Yacovo

    2014-11-01

    Full Text Available Introduction: Darunavir/r (DRV/r is currently used at a dose of 800/100 mg once daily (OD in a high proportion of patients. Pharmacokinetic data suggest that 600/100 OD may be effective, reducing toxicity and cost. However, drug concentrations in reservoirs such as cerebrospinal fluid (CSF might not be adequate to inhibit viral replication. We aimed to evaluate concentrations of DRV and HIV-1 viral load (VL in CSF patients receiving DRV 600/100 mg OD. Methods: DRV600 is an ongoing randomized open study comparing DRV/r 800/100 mg (DRV800 vs 600/100 mg (DRV600 OD plus TDF/FTC or ABC/3TC in 100 virologically suppressed patients (eudraCT 2011-006272-39. Here we present the results of a CSF sub-study. A lumbar puncture (LP was performed in participating patients after at least six months of inclusion in the study, 20–28 hours after a dose of DRV/r. VL (PCR, LOD 40 copies/mL was determined in CSF and in plasma. DRV concentrations were quantified in CSF by liquid chromatography mass spectrometry (LC/MS/MS and in plasma using high-performance liquid chromatography (HPLC. Results: Sixteen patients were included (eight in each arm. All DRV600 patients and four out of eight DRV800 patients received TDF/FTC, and the other four ABC/3TC. 75% were males, median (range age was 48 (17–71 years, CD4 cell count 532 cells/mL (190–1,394. Median total time on DRV/r was 30 (11–57 months, and since the beginning of the study 8 (6–12 months in DRV800 and 10 (7–12 months in DRV600 patients. LP was performed a median of 26 (24–28 hours after the last DRV/r+TVD or KVX dose. In DRV600 patients the median DRV plasma levels were 1,674 (326–3,742 ng/mL, CSF levels 17.08 (5.79–30.19 ng/mL and DRV CSF:plasma ratio 0.0084 (0.0028–0.0388, while in the DRV800 arm, median DRV plasma levels were 1,707 (958–3,910 ng/mL, CSF levels 13.23 (3.47–32.98 ng/mL and DRV CSF:plasma ratio 0.0104 (0.0018–0.0262. All patients had VL<40 copies/mL in plasma and 14 patients

  7. PGC-1beta is downregulated by training in human skeletal muscle: no effect of training twice every second day vs. once daily on expression of the PGC-1 family

    DEFF Research Database (Denmark)

    Mortensen, Ole Hartvig; Plomgaard, Peter; Fischer, Christian P;

    2007-01-01

    be observed in the acute response to endurance exercise. Furthermore, we hypothesized that expression levels of the PGC-1 family differ with muscular fiber-type composition. Thus, before and after 10 wk of knee extensor endurance training, training one leg once daily and the other leg twice daily every second...... endurance training, whereas PGC-1beta did not change. The mRNA levels of the PGC-1 family were examined in different types of human skeletal muscle (triceps, soleus, and vastus lateralis; n = 7). Only the expression level of PGC-1beta differed and correlated inversely with percentage of type I fibers......We hypothesized that the peroxisome proliferator-activated receptor-gamma coactivator-1 (PGC-1) family of transcriptional coactivators (PGC-1alpha, PGC-1beta, and PRC) is differentially regulated by training once daily vs. training twice daily every second day and that this difference might...

  8. Sulfasalazine and mesalamine modulate beryllium-specific lymphocyte proliferation and inflammatory cytokine production.

    Science.gov (United States)

    Dobis, Dave R; Sawyer, Richard T; Gillespie, May M; Newman, Lee S; Maier, Lisa A; Day, Brian J

    2010-10-01

    Occupational exposure to beryllium (Be) results in Be sensitization (BeS) that can progress to pulmonary granulomatous inflammation associated with chronic Be disease (CBD). Be-specific lymphocytes are present in the blood of patients with BeS and in the blood and lungs of patients with CBD. Sulfasalazine and its active metabolite, mesalamine, are clinically used to ameliorate chronic inflammation associated with inflammatory bowel disease. We tested whether sulfasalazine or mesalamine could decrease Be-stimulated peripheral blood mononuclear cell (PBMC) proliferation in subjects with CBD and BeS and Be-induced cytokine production in CBD bronchoalveolar lavage (BAL) cells. CBD (n = 25), BeS (n = 12) and healthy normal control (n = 6) subjects were enrolled and ex vivo proliferation and cytokine production were assessed in the presence of Be and sulfasalazine or mesalamine. Be-stimulated PBMC proliferation was inhibited by treatment with either sulfasalazine or mesalamine. Be-stimulated CBD BAL cell IFN-γ and TNF-α cytokine production was decreased by treatment with sulfasalazine or mesalamine. Our data suggest that both sulfasalazine and mesalamine interfere with Be-stimulated PBMC proliferation in CBD and BeS and dampens Be-stimulated CBD BAL cell proinflammatory cytokine production. These studies demonstrate that sulfasalazine and mesalamine can disrupt inflammatory pathways critical to the pathogenesis of chronic granulomatous inflammation in CBD, and may serve as novel therapy for human granulomatous lung diseases.

  9. A novel pH–enzyme-dependent mesalamine colon-specific delivery system

    Directory of Open Access Journals (Sweden)

    Jin L

    2016-06-01

    Full Text Available Lei Jin, Yi-cun Ding, Yu Zhang, Xiao-qing Xu, Qin Cao Department of Gastroenterology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China Abstract: The aim of the present study was to design a new pH–enzyme double-dependent mesalamine colon-specific delivery system. The drug release behaviors in vitro and pharmacokinetics and biodistribution in vivo were further evaluated. The mean particle diameters of mesalamine-coated microparticles were 312.2 µm. In vitro, a small amount of mesalamine was released in HCl at a pH of 1.2 and PBS medium at a pH of 7.4 for 5 hours, and 71% of the entrapped mesalamine was further released during the subsequent 20 hours of incubation. A greater area under the plasma concentration–time curve (AUC0–t was obtained for the coated microparticles (1.9-fold compared to the suspensions group, which indicated that the encapsulated mesalamine had mostly been absorbed in rats over the period of 12 hours. The AUC0–t of the coated microparticles in colon was 2.63-fold higher compared to the suspensions (P<0.05. Hence, mesalamine-coated microparticles are considered to maintain the drug concentration within target ranges for a long period of time. Keywords: pH–enzyme, mesalamine, colon specific, pharmacokinetics, biodistribution

  10. Barnidipine, a novel calcium antagonist for once-daily treatment of hypertension: a multicenter, double-blind, placebo-controlled, dose-ranging study. Dutch Barnidipine Multicenter Study Group.

    Science.gov (United States)

    Hart, W; Holwerda, N J

    1997-11-01

    The antihypertensive effects and tolerance of once-daily barnidipine, a novel dihydropyridine calcium antagonist, were evaluated. A total of 190 patients with a sitting diastolic blood pressure (DBP) of 95-114 mmHg were investigated in this multicenter, double-blind, placebo-controlled, dose-ranging study. After a 4-week single-blind placebo run-in period, patients were randomized to placebo or barnidipine (10 mg, 20 mg, or 30 mg modified release capsules) once daily for 6 weeks. Nonresponders (sitting DBP > or =90 mmHg and a decrease of barnidipine lowered blood pressure, with a trend toward a dose-response relationship over the dose range 10-30 mg. A dose increment of 10 mg in nonresponders resulted in additional reductions in blood pressure. At the end of the active treatment period, the responder rates were 41% and 57% for 10 mg and 20 mg barnidipine, respectively. Heart rate in both sitting and standing positions was not affected by barnidipine. Treatment with barnidipine was well tolerated, and the incidence of adverse events was dose related and consistent with vasodilatation. In conclusion, barnidipine (10-30 mg) administered once daily is well tolerated and reduces blood pressure in patients with mild to moderate hypertension.

  11. Long-term safety and efficacy of once-daily topical brimonidine tartrate gel 0.5% for the treatment of moderate to severe facial erythema of rosacea: results of a 1-year open-label study.

    Science.gov (United States)

    Moore, Angela; Kempers, Steven; Murakawa, George; Weiss, Jonathan; Tauscher, Amanda; Swinyer, Leonard; Liu, Hong; Leoni, Matthew

    2014-01-01

    Once-daily topical brimonidine tartrate (BT) gel 0.5% was shown to be efficacious and safe for the treatment of erythema of rosacea in previous studies including a 4-week treatment phase. In the present 1-year study, we aimed to assess the long-term safety and efficacy of the treatment. Subjects with moderate to severe erythema of rosacea were instructed to apply topical BT gel 0.5% once daily for 12 months. Severity of erythema and adverse events (AEs) were evaluated. Approximately 345 subject years of exposure to BT gel 0.5% was achieved in the study. The incidence of AEs and AEs judged to be related to the study drug was higher at the beginning and decreased over the course of the study. Similar safety profiles were observed between the subjects who had received or not received concomitant therapies for the inflammatory lesions of rosacea. Effect of topical BT gel 0.5% on erythema severity was observed after the first application and the durability of the effect was maintained until the end of the study at month 12, with no tachyphylaxis observed. In conclusion, once-daily topical BT gel 0.5% is safe and consistently effective for the long-term treatment of moderate to severe erythema of rosacea, even in the presence of concomitant therapies for the inflammatory lesions of rosacea.

  12. Efficacy, safety and pharmacokinetic of once-daily boosted saquinavir (1500/100 mg together with 2 nucleos(tide reverse transcriptase inhibitors in real life: a multicentre prospective study

    Directory of Open Access Journals (Sweden)

    Terrón Alberto

    2010-03-01

    Full Text Available Abstract Background Ritonavir-boosted saquinavir (SQVr is nowadays regarded as an alternative antiretroviral drug probably due to several drawbacks, such as its high pill burden, twice daily dosing and the requirement of 200 mg ritonavir when given at the current standard 1000/100 mg bid dosing. Several once-daily SQVr dosing schemes have been studied with the 200 mg SQV old formulations, trying to overcome some of these disadvantages. SQV 500 mg strength tablets became available at the end of 2005, thus facilitating a once-daily regimen with fewer pills, although there is very limited experience with this formulation yet. Methods Prospective, multicentre study in which efficacy, safety and pharmacokinetics of a regimen of once-daily SQVr 1500/100 mg plus 2 NRTIs were evaluated under routine clinical care conditions in either antiretroviral-naïve patients or in those with no previous history of antiretroviral treatments and/or genotypic resistance tests suggesting SQV resistance. Plasma SQV trough levels were measured by HPLV-UV. Results Five hundred and fourteen caucasian patients were included (47.2% coinfected with hepatitis C and/or B virus; 7.8% with cirrhosis. Efficacy at 52 weeks (plasma RNA-HIV 95: 63.6 - 71.7% by intention-to-treat, and 92.2% (CI95: 89.8 - 94.6% by on-treatment analysis. The reasons for failure were: dropout or loss to follow-up (18.4%, virological failure (7.8%, adverse events (3.1%, and other reasons (4.6%. The high rate of dropout may be explained by an enrollement and follow-up under routine clinical care condition, and a population with a significant number of drug users. The median SQV Cmin (n = 49 was 295 ng/ml (range, 53-2172. The only variable associated with virological failure in the multivariate analysis was adherence (OR: 3.36; CI95, 1.51-7.46, p = 0.003. Conclusions Our results suggests that SQVr (1500/100 mg once-daily plus 2 NRTIs is an effective regimen, without severe clinical adverse events or

  13. Mesalamine induced symptom exacerbation of ulcerative colitis: Case report and brief discussion

    Institute of Scientific and Technical Information of China (English)

    Maneesh; Kumar; Gupta; Scott; Pollack; John; J; Hutchings

    2010-01-01

    This paper describes a rare case in which the oral ad-ministration of mesalamine resulted in the exacerbation of ulcerative colitis (UC) in a patient who was previously responsive to mesalamine and whose colitis had been in remission for eight years. Mesalamine and other 5-ami-nosalicylic acid compounds are the mainstay of treatment for UC; however up to 8% of patients are unable to take the medications due to intolerance or hypersensitivity reactions. Common drug reactions are fever, nausea, di-arrhea and abdominal pain; however, exacerbation of UC has rarely been reported. This study highlights the impor-tance of ruling out mesalamine as the causative agent in cases of UC exacerbations.

  14. Mesalamine-induced myocarditis following diagnosis of Crohn's disease: a case report.

    Science.gov (United States)

    Galvão Braga, Carlos; Martins, Juliana; Arantes, Carina; Ramos, Vítor; Vieira, Catarina; Salgado, Alberto; Magalhães, Sónia; Correia, Adelino

    2013-09-01

    Mesalamine is a common treatment for Crohn's disease, and can be rarely associated with myocarditis through a mechanism of drug hypersensitivity. We present the case of a 19-year-old male who developed chest pain two weeks after beginning mesalamine therapy. The electrocardiogram showed slight ST-segment elevation with upward concavity in the inferolateral leads; blood tests demonstrated elevated troponin I and the echocardiogram revealed moderately depressed left ventricular systolic function with global hypocontractility. Cardiac magnetic resonance imaging confirmed the diagnosis of myocarditis, revealing multiple areas of subepicardial fibrosis. The onset of symptoms after mesalamine, and improvement of chest pain, cardiac biomarkers and left ventricular systolic function after discontinuing the drug, suggest that our patient suffered from a rare drug-hypersensitivity reaction to mesalamine.

  15. PGC-1beta is downregulated by training in human skeletal muscle: no effect of training twice every second day vs. once daily on expression of the PGC-1 family.

    Science.gov (United States)

    Mortensen, Ole Hartvig; Plomgaard, Peter; Fischer, Christian P; Hansen, Anne K; Pilegaard, Henriette; Pedersen, Bente Klarlund

    2007-11-01

    We hypothesized that the peroxisome proliferator-activated receptor-gamma coactivator-1 (PGC-1) family of transcriptional coactivators (PGC-1alpha, PGC-1beta, and PRC) is differentially regulated by training once daily vs. training twice daily every second day and that this difference might be observed in the acute response to endurance exercise. Furthermore, we hypothesized that expression levels of the PGC-1 family differ with muscular fiber-type composition. Thus, before and after 10 wk of knee extensor endurance training, training one leg once daily and the other leg twice daily every second day, keeping the total amount of training for the legs equal, skeletal muscle mRNA expression levels of PGC-1alpha, PGC-1beta, and PRC were determined in young healthy men (n = 7) in response to 3 h of acute exercise. No significant difference was found between the two legs, suggesting that regulation of the PGC-1 family is independent of training protocol. Training decreased PGC-1beta in both legs, whereas PGC-1alpha was increased, but not significantly, in the leg training once daily. PRC did not change with training. Both PGC-1alpha and PRC were increased by acute exercise both before and after endurance training, whereas PGC-1beta did not change. The mRNA levels of the PGC-1 family were examined in different types of human skeletal muscle (triceps, soleus, and vastus lateralis; n = 7). Only the expression level of PGC-1beta differed and correlated inversely with percentage of type I fibers. In conclusion, there was no difference between training protocols on the acute exercise and training response of the PGC-1 family. However, training caused a decrease in PGC-1beta mRNA levels.

  16. Novel Countercation in MMX-Type Mixed-Valence Chain Compound: Coexistence of Neutral and Protonated Amino Substituents

    Directory of Open Access Journals (Sweden)

    Hiroaki Iguchi

    2011-10-01

    Full Text Available The first MMX-type quasi-one-dimensional (Q1D Pt chain complex (MMX chain that contains a mono-protonated diamine as countercation, {o-(H3NC6H4NH2}4[Pt2(pop4I]·H2O (pop = P2H2O52–, was synthesized. According to the crystal structural analysis, –NH2 group was hydrogen-bonded to either lattice H2O molecule or –NH3+ group in addition to typical hydrogen bond between –NH3+ group and pop ligand. To control the partial deprotonation of the countercation will be an important method for achieving the high-conductive MMX-chain polymer by the hole doping.

  17. A 1-year study to compare the efficacy and safety of once-daily travoprost 0.004%/timolol 0.5% to once-daily latanoprost 0.005%/timolol 0.5% in patients with open-angle glaucoma or ocular hypertension.

    Science.gov (United States)

    Topouzis, F; Melamed, S; Danesh-Meyer, H; Wells, A P; Kozobolis, V; Wieland, H; Andrew, R; Wells, D

    2007-01-01

    The objective of the study was to compare the intraocular pressure (IOP)-lowering efficacy and safety of travoprost 0.004%/timolol 0.5% ophthalmic solution (Trav/Tim) to latanoprost 0.005%/timolol 0.5% ophthalmic solution (Lat/Tim), dosed once daily in the morning, in patients with open-angle glaucoma (OAG) or ocular hypertension (OH). This was a randomized, double-masked, multicenter, parallel group, active-controlled study conducted at 41 sites. At the eligibility visit the patients were randomized (1:1) to the assigned masked medication if they met inclusion/exclusion criteria, and the mean IOP values in the eligible eyes were > or =24 mmHg at 9 AM and > or =21 mmHg at 11 AM and 4 PM. Patients were excluded if the mean IOP in either eye was >36 mmHg. Patients were instructed to administer the assigned medication each morning at 9 AM. During the treatment phase of the study, IOP was measured at 9 AM at week 2, week 6, month 3, and month 9. At the month 6 and month 12 visits, IOP was measured at 9 AM, 11 AM, and 4 PM. Statistical methods included a repeated measures analysis of variance (ANOVA); to test for noninferiority, a 95% confidence interval for the treatment group difference was constructed based on the ANOVA results for each time point at month 12. Patients (n=408) with OAG or OH were enrolled at 41 sites. One patient withdrew prior to receiving medication so 207 in the Trav/Tim group and 200 in the Lat/Tim group were evaluable for safety. Baseline demographic characteristics as well as IOP values showed no statistical differences between the two groups. Trav/Tim provided lower mean IOP values than Lat/Tim that were statistically significant at the week 2 9 AM (p=0.0081), month 6 9 AM (p=0.0056), and month 6 11 AM (p=0.0128) time points and at 9 AM time point pooled across all visits (p=0.0235) when mean IOP was 0.6 mmHg lower in the Trav/Tim group. Treatment-related adverse events were mild in both groups. Although hyperemia was reported from a higher

  18. Attractiveness of MM-X traps baited with human or synthetic odor to mosquitoes (Diptera: Culicidae) in The Gambia.

    Science.gov (United States)

    Qiu, Yu Tong; Smallegange, Renate C; Ter, Braak Cajo J F; Spitzen, Jeroen; Van Loon, Joop J A; Jawara, Musa; Milligan, Paul; Galimard, Agnes M; Van Beek, Teris A; Knols, Bart G J; Takken, Willem

    2007-11-01

    Chemical cues play an important role in the host-seeking behavior of blood-feeding mosquitoes (Diptera: Culicidae). A field study was carried out in The Gambia to investigate the effects of human odor or synthetic odor blends on the attraction of mosquitoes. MM-X traps baited with 16 odor blends to which carbon dioxide (CO2) was added were tested in four sets of experiments. In a second series of experiments, MM-X traps with 14 odor blends without CO2 were tested. A blend of ammonia and L-lactic acid with or without CO2 was used as control odor in series 1 and 2, respectively. Centers for Disease Control and Prevention (CDC) traps were placed in a traditional house and an experimental house to monitor mosquito densities during the experiments. The MM-X traps caught a total number of 196,756 mosquitoes, with the most abundant species belonging to the genera Mansonia (70.6%), Anopheles (17.5%), and Culex (11.5%). The most abundant mosquito species caught by the CDC traps (56,290 in total) belonged to the genera Mansonia (59.4%), Anopheles (16.0% An. gambiae s.l. Giles, and 11.3% An. ziemanni Grünberg), and Culex (11.6%). MM-X traps baited with synthetic blends were in many cases more attractive than MM-X traps baited with human odors. Addition of CO2 to synthetic odors substantially increased the catch of all mosquito species in the MM-X traps. A blend of ammonia + L-lactic acid + CO, + 3-methylbutanoic acid was the most attractive odor for most mosquito species. The candidate odor blend shows the potential to enhance trap collections so that traps will provide better surveillance and possible control.

  19. Attractiveness of MM-X traps baited with human or synthetic odor to mosquitoes (Diptera: Culicidae) in The Gambia

    NARCIS (Netherlands)

    Qiu, Y.T.; Smallegange, R.C.; Braak, ter C.J.F.; Spitzen, J.; Loon, van J.J.A.; Jawara, M.; Milligan, P.; Galimard, A.M.S.; Beek, van T.A.; Knols, B.G.J.; Takken, W.

    2007-01-01

    Chemical cues play an important role in the host-seeking behavior of blood-feeding mosquitoes (Diptera: Culicidae). A field study was carried out in The Gambia to investigate the effects of human odor or synthetic odor blends on the attraction of mosquitoes. MM-X traps baited with 16 odor blends to

  20. Lung function efficacy and symptomatic benefit of olodaterol once daily delivered via Respimat® versus placebo and formoterol twice daily in patients with GOLD 2–4 COPD: results from two replicate 48-week studies

    Directory of Open Access Journals (Sweden)

    Koch A

    2014-07-01

    Full Text Available Andrea Koch,1 Emilio Pizzichini,2 Alan Hamilton,3 Lorna Hart,3 Lawrence Korducki,4 Maria Cristina De Salvo,5 Pierluigi Paggiaro6 1Medical Clinic III for Pneumology, Allergology, Sleep and Respiratory Medicine, University Hospital Bochum-Bergmannsheil, Bochum, Germany; 2NUPAIVA (Asthma Research Center, Universidade Federal de Santa Catarina, Santa Catarina, Brazil; 3Boehringer Ingelheim, Burlington, Ontario, Canada; 4Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, USA; 5Centro Médico Dra. De Salvo, Fundación Respirar, Buenos Aires, Argentina; 6Cardio-Thoracic and Vascular Department, University of Pisa, Pisa, Italy Abstract: Two replicate, multicenter, randomized, double-blind, placebo-controlled, parallel-group, Phase III studies investigated the long-term efficacy and safety of once-daily olodaterol via Respimat® versus placebo and formoterol over 48 weeks in patients with moderate to very severe chronic obstructive pulmonary disease receiving usual-care background therapy. Patients received once-daily olodaterol 5 or 10 µg, twice-daily formoterol 12 µg, or placebo. Co-primary end points were forced expiratory volume in 1 second (FEV1 area under the curve from 0–3 hours response, FEV1 trough response, and Mahler transition dyspnea index total score after 24 weeks; secondary end points included St George's Respiratory Questionnaire. Overall, 904 (Study 1222.13 and 934 (Study 1222.14 patients received treatment. Olodaterol significantly improved FEV1 area under the curve from 0–3 hours versus placebo in both studies (with olodaterol 5 µg, 0.151 L and 0.129 L; with olodaterol 10 µg, 0.165 L and 0.154 L; for all comparisons P<0.0001 and FEV1 trough responses versus placebo (0.053–0.085 L; P<0.01, as did formoterol. Primary analysis revealed no significant difference in transition dyspnea index focal score for any active treatment versus placebo. Post hoc analysis using pattern mixture modeling (accounting for

  1. Monotherapy with indacaterol once daily reduces the rate of exacerbations in patients with moderate-to-severe COPD: Post-hoc pooled analysis of 6 months data from three large phase III trials.

    Science.gov (United States)

    Wedzicha, Jadwiga A; Buhl, Roland; Lawrence, David; Young, David

    2015-01-01

    In patients with COPD, exacerbations are associated with poor quality of life and may shorten survival. Prevention of exacerbations is, therefore, a key objective in COPD management. Indacaterol, a once-daily ultra-long-acting β2-agonist, has been shown to reduce exacerbations in various studies. This pooled analysis evaluated the effect of indacaterol on exacerbations versus placebo. Six-month data were pooled from three randomized, double-blind, and placebo-controlled studies: indacaterol 300 μg versus placebo (1 year); indacaterol 150 μg and 300 μg versus placebo (6 months); and indacaterol 150 μg versus placebo (6 months). All treatments were administered once daily. Data from other treatment groups were excluded. All three studies enrolled patients aged ≥40 years with moderate-to-severe COPD and smoking history ≥20 pack-years. Time to exacerbation and exacerbation rate were analyzed. Overall, the pooled data set included 2716 patients (indacaterol 150 μg [n = 746], indacaterol 300 μg [n = 819], placebo [n = 1151]). Both indacaterol doses 150 and 300 μg significantly reduced the COPD exacerbation rates compared with placebo (Rate ratios, RR [95% Confidence Interval, CI]: 0.69 [0.55-0.87], 0.71 [95% CI: 0.57-0.88] respectively; both p = 0.002). Over 6 months, indacaterol 150 and 300 μg also significantly prolonged the time to first moderate-to-severe exacerbation versus placebo (Hazard ratios, HR [95% CI]: 0.74: [0.59-0.93], p = 0.009; 0.73 [0.59-0.90], p = 0.004, respectively). At months 3 and 6, clinically relevant improvements in lung function versus placebo were observed with indacaterol 150 μg (Least squares mean treatment differences: Month 3 = 170 mL; Month 6 = 160 mL) and 300 μg (170 mL at both time-points; all p indacaterol doses, 150 and 300 μg, were associated with significant reductions in exacerbations and significant improvements in bronchodilation versus placebo. The results suggest once-daily indacaterol is an effective treatment

  2. Mesalamine suppresses the expression of TC22, a novel tropomyosin isoform associated with colonic neoplasia.

    Science.gov (United States)

    Das, Koushik K; Bajpai, Manisha; Kong, Yingxin; Liu, Jianying; Geng, Xin; Das, Kiron M

    2009-07-01

    Although a protective role for mesalamine against colon cancer in ulcerative colitis has been shown epidemiologically, its molecular mechanism is unknown. We cloned and sequenced a novel human tropomyosin (hTM) isoform, TC22, which is an alternatively spliced variant of normal epithelial hTM isoform 5 (hTM5), identical apart from 25 C-terminal amino acids. TC22 is expressed in 100% of colorectal carcinoma but is not expressed in normal colon epithelial cells. To explore a molecular mechanism of chemoprevention, we examined the effect of mesalamine on TC22 expression using LS180 colon cancer cells. Expression of hTM5 and TC22 was investigated at the protein and gene levels by fluorescence-activated cell sorting and real-time reverse transcription-polymerase chain reaction. Small interference RNA (siRNA) against the TC22 variant were transfected into LS180 colon cancer cells, reducing protein and transcript levels by 45 to 50%. Mesalamine or sulfasalazine (2 mM), but not sulfapyridine, significantly (p mesalamine, sulfasalazine, and rosiglitazone significantly reduced the cellular expression of TC22, implicating PPARgamma in this modulation. Similar suppression of TC22 by siRNA produced gene level changes on several critical carcinogenic pathways. These findings suggest a novel antineoplastic molecular effect of mesalamine.

  3. Discovery of a Potent Acyclic, Tripeptidic, Acyl Sulfonamide Inhibitor of Hepatitis C Virus NS3 Protease as a Back-up to Asunaprevir with the Potential for Once-Daily Dosing.

    Science.gov (United States)

    Sun, Li-Qiang; Mull, Eric; Zheng, Barbara; D'Andrea, Stanley; Zhao, Qian; Wang, Alan Xiangdong; Sin, Ny; Venables, Brian L; Sit, Sing-Yuen; Chen, Yan; Chen, Jie; Cocuzza, Anthony; Bilder, Donna M; Mathur, Arvind; Rampulla, Richard; Chen, Bang-Chi; Palani, Theerthagiri; Ganesan, Sivakumar; Arunachalam, Pirama Nayagam; Falk, Paul; Levine, Steven; Chen, Chaoqun; Friborg, Jacques; Yu, Fei; Hernandez, Dennis; Sheaffer, Amy K; Knipe, Jay O; Han, Yong-Hae; Schartman, Richard; Donoso, Maria; Mosure, Kathy; Sinz, Michael W; Zvyaga, Tatyana; Rajamani, Ramkumar; Kish, Kevin; Tredup, Jeffrey; Klei, Herbert E; Gao, Qi; Ng, Alicia; Mueller, Luciano; Grasela, Dennis M; Adams, Stephen; Loy, James; Levesque, Paul C; Sun, Huabin; Shi, Hong; Sun, Lucy; Warner, William; Li, Danshi; Zhu, Jialong; Wang, Ying-Kai; Fang, Hua; Cockett, Mark I; Meanwell, Nicholas A; McPhee, Fiona; Scola, Paul M

    2016-09-08

    The discovery of a back-up to the hepatitis C virus NS3 protease inhibitor asunaprevir (2) is described. The objective of this work was the identification of a drug with antiviral properties and toxicology parameters similar to 2, but with a preclinical pharmacokinetic (PK) profile that was predictive of once-daily dosing. Critical to this discovery process was the employment of an ex vivo cardiovascular (CV) model which served to identify compounds that, like 2, were free of the CV liabilities that resulted in the discontinuation of BMS-605339 (1) from clinical trials. Structure-activity relationships (SARs) at each of the structural subsites in 2 were explored with substantial improvement in PK through modifications at the P1 site, while potency gains were found with small, but rationally designed structural changes to P4. Additional modifications at P3 were required to optimize the CV profile, and these combined SARs led to the discovery of BMS-890068 (29).

  4. Morning and evening behavior in children and adolescents treated with atomoxetine once daily for Attention-Deficit/Hyperactivity Disorder (ADHD: Findings from two 24-week, open-label studies

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    Schacht Alexander

    2009-02-01

    Full Text Available Abstract Background The impact of once daily atomoxetine treatment on symptoms in children and adolescents with ADHD may vary over the day. In order to capture such variations, two studies were undertaken in children and adolescents with ADHD using two instruments that capture morning and evening behavior and ADHD-related difficulties over the day. This secondary measure analysis builds on two primary analyses that were conducted separately for children and adolescents and also published separately. Methods In two open-label studies, ADHD patients aged 6–17 years (n = 421, received atomoxetine in the morning (target-dose 0.5–1.2 mg/kg/day for up to 24 weeks. Morning and evening behavior was assessed using the investigator-rated Weekly Rating of Evening and Morning Behavior (WREMB-R scale. ADHD-related difficulties at various times of the day (morning, during school, during homework, evening were assessed using the Global Impression of Perceived Difficulties (GIPD scale, rated by patients, parents and physicians. Data from both studies were combined for this secondary measure analysis. Results Both WREMB-R subscores decreased significantly over time, the evening subscore from 13.7 (95% CI 13.2;14.2 at baseline to 8.0 (7.4;8.5 at week 2, the morning subscore from 4.3 (4.0;4.5 to 2.4 (2.2;2.6. Scores then remained stable until week 24. All GIPD items improved correspondingly. At all times of the day, patients rated ADHD-related difficulties as less severe than parents and physicians. Conclusion These findings from two open-label studies suggest that morning and evening behavior and ADHD-related difficulties in the mornings and evenings improve over time with once daily atomoxetine treatment.

  5. Mesalamine-Induced Myocarditis and Coronary Vasculitis in a Pediatric Ulcerative Colitis Patient: A Case Report

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    Elimarys Perez-Colon

    2011-01-01

    Full Text Available Mesalamine-containing products are often a first-line treatment for ulcerative colitis. Severe adverse reactions to these products, including cardiovascular toxicity, are rarely seen in pediatric patients. We present a case of a 16-year-old boy with ulcerative colitis treated with Asacol, a mesalamine-containing product, who developed sudden onset chest pain after four weeks on therapy. Serial electrocardiograms showed nonspecific ST segment changes, an echocardiogram showed mildly decreased left ventricular systolic function with mild to moderate left ventricular dilation and coronary ectasia, and his troponins were elevated. Following Asacol discontinuation, his chest pain resolved, troponins were trending towards normal, left ventricular systolic function normalized, and coronary ectasia improved within 24 hours suggesting an Asacol-associated severe drug reaction. Mesalamine-induced cardiovascular toxicity, although rare, may represent a life-threatening disorder. Therefore, every patient presenting with acute chest pain should receive a workup to rule out this rare drug-induced disorder.

  6. Simple and sensitive spectrophotometric methods for the analysis of mesalamine in bulk and tablet dosage forms

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    Bala Sekaran Chandra

    2011-01-01

    Full Text Available Three simple, sensitive, economical and reproducible spectrophotometric methods (A, B and C are described for determination of mesalamine in pure drug as well as in tablet dosage forms. Method A is based on the reduction of tungstate and/or molybdate in Folin Ciocalteu's reagent; method B describes the reaction between the diazotized drug and α-naphthol and method C is based on the reaction of the drug with vanillin, in acidic medium. Under optimum conditions, mesalamine could be quantified in the concentration ranges, 1-30, 1-15 and 2-30 µg mL-1 by method A, B and C, respectively. All the methods have been applied to the determination of mesalamine in tablet dosage forms. Results of analysis are validated statistically.

  7. Mesalamine-induced myopericarditis in a paediatric patient with Crohn's disease.

    Science.gov (United States)

    Nair, Asha G; Cross, Russell R

    2015-04-01

    Mesalamine-containing products are considered first-line treatment for inflammatory bowel disease. Myocarditis is recognised as a very rare possible side effect of these medications, but has not often been described in the paediatric population. We present a case of an adolescent with Crohn's disease who presented with myopericarditis after recent initiation of Pentasa. Once identified as the causative agent, the drug was discontinued, with subsequent normalisation of troponin and improvement of function. This case identifies the importance of prompt evaluation, diagnosis, and treatment of paediatric patients receiving mesalamine-containing medications that present with significant cardiovascular symptoms.

  8. Development of enteric coated sustained release minitablets containing mesalamine

    Directory of Open Access Journals (Sweden)

    Dayse Fernanda de Souza

    2013-09-01

    Full Text Available The aim of this study was to develop and evaluate a multiparticulate modified release system, composed of minitablets with a sustained release matrix system coated with a pH-dependent release polymer, using mesalamine as a model drug. Polyox® WSR 1105 was the polymer used in the matrix system and Eudragit® L30D55 was used as a pH-dependent polymer. The minitablets (with 20%, 30% or 40% Polyox® concentration were prepared by dry granulation, which led to good quality minitablets. The developed minitablets were coated in a fluidized bed at 8% of the coating level. Dissolution studies were performed in media that simulated the gastrointestinal tract (pH 1.4, 6.0 and 7.2 and showed that formulations with higher Polyox® concentrations were capable of retaining the drug release in pH 1.4. All formulations prolonged the drug release and presented zero-order kinetic behaviour. The Korsmeyer-Peppas model demonstrated that formulations with 20% or 30% of polymer exhibited anomalous transport behaviour, whilst the 40% sample exhibited super case II model transportation. Dissolution efficiency showed that only the formulations containing 20% and 40% polymer could be considered statistically different.

  9. Single-dose pharmacokinetics of once-daily cyclobenzaprine extended release 30 mg versus cyclobenzaprine immediate release 10 mg three times daily in healthy young adults : a randomized, open-label, two-period crossover, single-centre study.

    Science.gov (United States)

    Darwish, Mona; Hellriegel, Edward T; Xie, Fang

    2008-01-01

    Cyclobenzaprine immediate release (CIR) has shown efficacy in the treatment of muscle spasm associated with acute, painful musculoskeletal conditions. An extended-release formulation of cyclobenzaprine (CER) has been developed to provide effective muscle spasm relief with once-daily dosing. The objective of this study was to compare the pharmacokinetics of CER and CIR. This was a single-centre study of 18 healthy young adults (aged 18-45 years). Healthy volunteers were assigned to receive either a single dose of CER 30 mg or three doses of CIR 10 mg on days 1 and 15 (separated by a 14-day washout) in an open-label, two-period crossover study. Pharmacokinetic parameters were monitored through 168 hours after the last dose in each dose period; adverse events (AEs) were monitored during the study through 3 weeks after the last dose of study drug. Cyclobenzaprine was administered as a single oral 30 mg dose of CER or three 10 mg oral doses of CIR given every 8 hours over 24 hours. Statistical tests were conducted against a two-sided alternative hypothesis at a 0.05 level of significance with equivalence limits of 80% and 125%. Measures included area under the plasma cyclobenzaprine concentration versus time curve (AUC) to 168 hours and infinity, maximum plasma cyclobenzaprine concentration (C(max)), and time to observed C(max) (t(max)). Eighteen subjects were randomized and 17 completed both periods of the study. CER exhibited a consistent concentration-time profile with a single peak, in contrast to the pharmacokinetic profile for CIR, which displayed multiple peaks and troughs over the 24-hour period. The pharmacokinetic profile of CER 30 mg was characterized by an absorption phase with a median t(max) of approximately 6 hours, compared with the initial peak of CIR (following the first dose) of about 4 hours. Mean plasma concentrations at 4 hours were comparable (12.1 ng/mL for CER; 12.4 ng/mL for CIR). Systemic cyclobenzaprine exposure (AUC and C(max)) was similar

  10. Clinical and Pharmacokinetic Data Support Once-Daily Low-Dose Boosted Saquinavir (1,200 Milligrams Saquinavir with 100 Milligrams Ritonavir) in Treatment-Naive or Limited Protease Inhibitor-Experienced Human Immunodeficiency Virus-Infected Patients▿

    Science.gov (United States)

    Marin-Niebla, Ana; Lopez-Cortes, Luis Fernando; Ruiz-Valderas, Rosa; Viciana, Pompeyo; Mata, Rosario; Gutierrez, Alicia; Pascual, Rosario; Rodriguez, Magdalena

    2007-01-01

    We evaluated the plasma and intracellular pharmacokinetics, clinical efficacy, and safety of once-daily low-dose boosted saquinavir (SQVr; 1,200 of saquinavir [SQV] with 100 mg of ritonavir) plus two nucleotide reverse transcriptase inhibitors in treatment-naive or limited protease inhibitor (PI)-experienced human immunodeficiency virus (HIV)-infected patients. A prospective study without entry restrictions on the plasma HIV-RNA (VL) or CD4 cell count was carried out. Plasma and intracellular SQV levels were measured by high-performance liquid chromatography. Efficacy was evaluated by an intention-to-treat analysis; treatment failure was defined as virological failure (a VL of >50 copies/ml after 24 weeks or a confirmed rebound to >50 copies/ml) or interruption for any reason. A total of 151 patients were included in the study (106 of them either had never received PI or had no previous virological failure on PIs) and could be characterized as follows: previous C3 stage, 28.9%; injection-drug users, 69.1%; subjects with chronic viral hepatitis, 53%; and subjects with cirrhosis, 10%. The median baseline CD4 level was 184/μl, and the median VL was 4.8 log10 copies/ml. Median Cmax, area under the concentration-time curve from 0 to 24 h, and Cmin plasma and intracellular SQV levels were 3,672 and 10,105 ng/ml, 34,283 and 99,535 ng·h/ml, and 359 and 1,062 ng/ml, respectively. The efficacy as determined by intention to treat at 52 weeks was 69.7% (96% in the on-treatment analysis), with similar results regardless of the baseline VL and CD4 counts. Only five patients had virological failure despite adequate Cmin levels, but with a poor adherence (the only variable related to virological failure). Adverse events caused the withdrawal of the treatment in four patients (2.6%). In conclusion, given the pharmacokinetic profile, efficacy, and tolerability of this regimen, once-daily low-dose SQVr may be considered a treatment option in treatment-naive or limited PI

  11. Software Optimization of Video Codecs on Pentium Processor with MMX Technology

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    Liu KJ Ray

    2001-01-01

    Full Text Available A key enabling technology for the proliferation of multimedia PC's is the availability of fast video codecs, which are the basic building blocks of many new multimedia applications. Since most industrial video coding standards (e.g., MPEG1, MPEG2, H.261, H.263 only specify the decoder syntax, there are a lot of rooms for optimization in a practical implementation. When considering a specific hardware platform like the PC, the algorithmic optimization must be considered in tandem with the architecture of the PC. Specifically, an algorithm that is optimal in the sense of number of operations needed may not be the fastest implementation on the PC. This is because special instructions are available which can perform several operations at once under special circumstances. In this work, we describe a fast implementation of H.263 video encoder for the Pentium processor with MMX technology. The described codec is adopted for video mail and video phone softwares used in IBM ThinkPad.

  12. MMX-I: A data-processing software for multi-modal X-ray imaging and tomography

    Science.gov (United States)

    Bergamaschi, A.; Medjoubi, K.; Messaoudi, C.; Marco, S.; Somogyi, A.

    2017-06-01

    Scanning hard X-ray imaging allows simultaneous acquisition of multimodal information, including X-ray fluorescence, absorption, phase and dark-field contrasts, providing structural and chemical details of the samples. Combining these scanning techniques with the infrastructure developed for fast data acquisition at Synchrotron Soleil permits to perform multimodal imaging and tomography during routine user experiments at the Nanoscopium beamline. A main challenge of such imaging techniques is the online processing and analysis of the generated very large volume (several hundreds of Giga Bytes) multimodal data-sets. This is especially important for the wide user community foreseen at the user oriented Nanoscopium beamline (e.g. from the fields of Biology, Life Sciences, Geology, Geobiology), having no experience in such data-handling. MMX-I is a new multi-platform open-source freeware for the processing and reconstruction of scanning multi-technique X-ray imaging and tomographic datasets. The MMX-I project aims to offer, both expert users and beginners, the possibility of processing and analysing raw data, either on-site or off-site. Therefore we have developed a multi-platform (Mac, Windows and Linux 64bit) data processing tool, which is easy to install, comprehensive, intuitive, extendable and user-friendly. MMX-I is now routinely used by the Nanoscopium user community and has demonstrated its performance in treating big data.

  13. Efficacy, adherence and tolerability of once daily tenofovir DF-containing antiretroviral therapy in former injecting drug users with HIV-1 receiving opiate treatment: results of a 48-week open-label study

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    Esser S

    2011-10-01

    Full Text Available Abstract Objective To assess efficacy, adherence and tolerability of once daily antiretroviral therapy containing tenofovir disoproxil fumarate (DF 300 mg in HIV-1-infected former injecting drug users receiving opiate treatment (IVDU. Methods European, 48-week, open-label, single-arm, multicenter study. Patients were either antiretroviral therapy-naïve, restarting therapy after treatment discontinuation without prior virological failure or switching from existing stable treatment. Results Sixty-seven patients were enrolled in the study and 41 patients completed treatment. In the primary analysis (intent-to-treat missing = failure at week 48, 34% of patients (23/67; 95% CI: 23%-47% had plasma HIV-1 RNA 3. Although self-reported adherence appeared high, there were high levels of missing data and adherence results should be treated with caution. No new safety issues were identified. Conclusions Levels of missing data were high in this difficult-to-treat population, but potent antiretroviral suppression was achieved in a substantial proportion of HIV-infected IVDU-patients.

  14. Optimization of health-care organization and perceived improvement of patient comfort by switching from intra-venous BU four-times-daily infusions to a once-daily administration scheme in adult hematopoietic stem cell recipients.

    Science.gov (United States)

    Xhaard, A; Rzepecki, P; Valcarcel, D; Santarone, S; Fürst, S; Serrano, D; De Angelis, G; Krüger, W; Scheid, C

    2014-04-01

    Previous studies have shown an equivalent pharmacokinetic profile between four-times-daily (4QD) and once-daily (QD) administration of intra-venous (IV) BU, without increased toxicity. We assess the impact of a switch in IV BU from a 4QD to a QD schedule, in terms of health-care organization, staff working conditions, quality of care dispensed and perceived patient comfort. Clinicians, nurses and pharmacists from nine allogeneic transplantation units in five European countries were interviewed face to face. Overall perception of QD versus 4QD BU was very positive. Both administration schemes were evaluated to be equally efficaciousZ. QD BU was perceived to be safer and more convenient. Clinicians and nurses perceived that patient comfort was improved, due to fewer complications associated with repeated infusions, and avoiding night infusions associated with stress, anxiety and decreased quality of sleep. Switching from 4QD to QD BU had a significant impact on health-care organization, with a better integration in the overall management and usual timelines in the pharmacies and transplantation units. Time spent to prepare and administer BU was significantly reduced, leading to potential financial savings that merit further assessment and would be of particular interest in the current economic climate.

  15. A prospective, randomized, double dummy, placebo-controlled trial of oral cefditoren pivoxil 400mg once daily as switch therapy after intravenous ceftriaxone in the treatment of acute pyelonephritis.

    Science.gov (United States)

    Monmaturapoj, Teerapong; Montakantikul, Preecha; Mootsikapun, Piroon; Tragulpiankit, Pramote

    2012-12-01

    To compare the clinical and bacteriological effectiveness of intravenous (IV) ceftriaxone followed by oral cefditoren pivoxil or IV ceftriaxone for acute pyelonephritis. A prospective randomized controlled trial of patients with a presumptive diagnosis of acute pyelonephritis was performed. Daily 2g IV ceftriaxone was initially given to all patients. After day 3, patients who satisfied the criteria for switch therapy were randomized to either group A (IV ceftriaxone) or group B (oral cefditoren pivoxil 400mg once daily). Eighty-two patients were enrolled; 41 (50%) patients in group A and 41 (50%) patients in group B were evaluated. There was no statistically significant difference in baseline characteristics between the two groups. Clinical cure was observed in 39 of 41 (95.1%) patients in group A and 41 of 41 (100%) patients in group B (p=0.15, 95% confidence interval (CI) -0.12 to 0.02). Urine bacteriological eradication was found in 63.4% in group A and 60% in group B (p=0.75, 95% CI -0.18 to 0.25). There was no statistically significant difference in adverse effects between the two treatment groups. These data suggest that IV ceftriaxone followed by oral cefditoren pivoxil is highly effective and well-tolerated for the treatment of acute pyelonephritis, even for uropathogens with a high proportion of quinolone-resistant strains. Copyright © 2012 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  16. Treatment with liraglutide--a once-daily GLP-1 analog--does not reduce the bioavailability of ethinyl estradiol/levonorgestrel taken as an oral combination contraceptive drug.

    Science.gov (United States)

    Jacobsen, Lisbeth V; Vouis, Jan; Hindsberger, Charlotte; Zdravkovic, Milan

    2011-12-01

    Liraglutide is a once-daily human GLP-1 analog for treatment of type 2 diabetes. Like other GLP-1 analogs, liraglutide delays gastric emptying, which could potentially affect absorption of concomitantly administered oral drugs. This study investigated the effect of liraglutide on the pharmacokinetics of the components of an oral contraceptive (ethinyl estradiol/levonorgestrel). Postmeno-pausal healthy women (n = 21) were included. A single dose of this contraceptive was administered. Blood samples for ethinyl estradiol/levonorgestrel measurements were drawn until 74 hours post dosing of the contraceptive during liraglutide and placebo treatments. The 90% confidence interval (CI) of the ratio of the area under the curve (AUC) (1.06; 90% CI, 0.99-1.13) for ethinyl estradiol (during liraglutide and placebo) was within defined limits, demonstrating equivalence. The 90% CI for the ratio of AUC for levonorgestrel was not fully contained within the limits (1.18; 90% CI, 1.04-1.34) (levonorgestrel AUC was 18% greater with liraglutide vs placebo). However, equivalence was demonstrated for levonorgestrel AUC(0-t) (1.15; 90% CI, 1.06-1.24). Equivalence was not demonstrated for maximum concentration (C(max)); values for ethinyl estradiol and levonorgestrel C(max) were 12% and 13% lower with liraglutide versus placebo, respectively. Both reached C(max) ~1.5 hours later with liraglutide. No clinically relevant reduction in bioavailability of ethinyl estradiol/levonorgestrel occurred.

  17. Efficacy and Safety of Once-Daily Insulin Degludec/Insulin Aspart versus Insulin Glargine (U100) for 52 Weeks in Insulin-Naïve Patients with Type 2 Diabetes: A Randomized Controlled Trial

    Science.gov (United States)

    Kumar, Ajay; Franek, Edward; Wise, Jonathan; Niemeyer, Marcus; Mersebach, Henriette; Simó, Rafael

    2016-01-01

    Purpose The efficacy and safety of insulin degludec/insulin aspart (IDegAsp) once daily (OD) compared with insulin glargine U100 (IGlar) OD over 52 weeks in insulin-naïve adults with type 2 diabetes mellitus (T2DM) was investigated. Methods In this open-label, parallel-group treat-to-target trial, participants were randomized (1:1) to receive IDegAsp OD (breakfast, n = 266) or IGlar OD (as per label, n = 264). Participants then entered a 26-week extension phase (IDegAsp OD, n = 192; IGlar OD, n = 221). The primary endpoint was change from baseline to Week 26 in HbA1c. Results After 26 and 52 weeks, mean HbA1c decreased to similar levels in both groups. After 52 weeks, the mean estimated treatment difference was –0.08% (–0.26, 0.09 95%CI), confirming the non-inferiority of IDegAsp OD versus IGlar OD evaluated at Week 26. After 52 weeks, there was a similar reduction in mean fasting plasma glucose in both treatment groups. The rate of confirmed hypoglycemic episodes was 86% higher (p administration of IDegAsp with the main meal of the day, tailored to the individual patient’s needs. Trial Registration ClinicalTrials.gov: NCT01045707 [core]) and NCT01169766 [ext] PMID:27760129

  18. Determination of Mesalamine Related Impurities from Drug Product by Reversed Phase Validated UPLC Method

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    Trivedi Rakshit Kanubhai

    2011-01-01

    Full Text Available In the present study gradient reversed-phase UPLC method was developed for simultaneous determination and separation of impurities and degradation products from drug product. The chromatographic separation was performed on acquity UPLC BEH C18 column (50 mm×2.1 mm, 1.7 µm using gradient elution. Other UPLC parameters which were optimised are flow rate, 0.7 mL/min; detection wavelength, 220 nm; column oven temperature, 40 °C and injection volume 7 µL. Stability indicating capability was established by forced degradation experiments and separation of known degradation products. The method was validated as per International Conference on Harmonization (ICH guideline. For all impurities and mesalamine, LOQ (limit of quantification value was found precise with RSD (related standard daviation of less than 2.0%. In essence, the present study provides an improved low detection limit and lower run time for evaluation of pharmaceutical quality of mesalamine delayed-release formulation. Moreover, the developed method was successfully applied for quantification of impurities and degradation products in mesalamine delayed-release formulation. The same method can also be used for determination of related substances from mesalamine drug substance.

  19. Individually administered or co-prescribed thiopurines and mesalamines for inflammatory bowel disease

    Institute of Scientific and Technical Information of China (English)

    Giovanni C Actis; Rinaldo Pellicano; Mario Rizzetto; Muhammad Ayoubi; Nicola Leone; Gianfranco Tappero; Paola Pazienza; Floriano Rosina

    2009-01-01

    Data from both basic research and clinical experience continue to suggest that mesalamines and thiopurines are effective and efficient for the maintenance of remission of inflammatory bowel diseases. Several decades following the formalization of their indications, attention on these two drugs has been fostered by recent achievements. Demonstration of the ability of mesalamine to activate a colonocyte differentiation factor has shed light on its chemopreventive effects on colorectal cancer;in addition to their anti-proliferative efficacy, thiopurines have been shown to be specific regulators of apoptosis. The two drugs are often coadministered in clinical practice. Recent advancements have shown that mesalamines exert a positive synergism in this context, insofar as they can inhibit sidemethylation of thiopurines and hasten the function of the main immunosuppressive pathways. Considering that up to 40% of patients cannot tolerate thiopurines, such renovated targets have stimulated efforts to improve compliance by research on the toxicity mechanisms. The definition of genetic polymorphisms in the enzymes of thiopurine metabolism, and the uncovering of synergistic drug interactions, such as that with allopurinol, are just two of the results of such efforts. Interaction between basic research and clinical practice between basic research and clinical practice has continued to inform indications and refin e the prescriptionsof mesalamines and thiopurines;these have not been restrained (they have been implem ented insome cases) by the advent of the novel biological molecules with anti-cytokine activity.

  20. Individually administered or co-prescribed thiopurines and mesalamines for inflammatory bowel disease.

    Science.gov (United States)

    Actis, Giovanni-C; Pellicano, Rinaldo; Rizzetto, Mario; Ayoubi, Muhammad; Leone, Nicola; Tappero, Gianfranco; Pazienza, Paola; Rosina, Floriano

    2009-03-28

    Data from both basic research and clinical experience continue to suggest that mesalamines and thiopurines are effective and efficient for the maintenance of remission of inflammatory bowel diseases. Several decades following the formalization of their indications, attention on these two drugs has been fostered by recent achievements. Demonstration of the ability of mesalamine to activate a colonocyte differentiation factor has shed light on its chemopreventive effects on colorectal cancer; in addition to their anti-proliferative efficacy, thiopurines have been shown to be specific regulators of apoptosis. The two drugs are often co-administered in clinical practice. Recent advancements have shown that mesalamines exert a positive synergism in this context, insofar as they can inhibit side-methylation of thiopurines and hasten the function of the main immunosuppressive pathways. Considering that up to 40% of patients cannot tolerate thiopurines, such renovated targets have stimulated efforts to improve compliance by research on the toxicity mechanisms. The definition of genetic polymorphisms in the enzymes of thiopurine metabolism, and the uncovering of synergistic drug interactions, such as that with allopurinol, are just two of the results of such efforts. Interaction between basic research and clinical practice has continued to inform indications and refine the prescriptions of mesalamines and thiopurines; these have not been restrained (they have been implemented in some cases) by the advent of the novel biological molecules with anti-cytokine activity.

  1. Benzimidazole--ibuprofen/mesalamine conjugates: potential candidates for multifactorial diseases.

    Science.gov (United States)

    Bansal, Yogita; Kaur, Maninder; Silakari, Om

    2015-01-07

    Ibuprofen (IB) and mesalamine (MES) are commonly used NSAIDs whereas benzimidazole (BZ) and 2-aminobenzimidazole (ABZ) are important pharmacophore for immunomodulatory activities. In the present study, IB and MES were coupled with variedly substituted BZ or ABZ nucleus to synthesize IB-BZ (2a-2e), IB-ABZ (3a-3e), MES-BZ (4a-4e) and MES-ABZ (5a-5e) chimeric conjugates as novel compounds that could elicit both anti-inflammatory and immunomodulatory activities. Each compound retained the anti-inflammatory activity of the parent NSAID. The BZ conjugates (2 and 4) were found immunostimulatory whereas the ABZ conjugates (3 and 5) were immunosuppressive. Each compound also exhibited good antioxidant activity, which is attributed to the electron rich BZ and ABZ nuclei. Compound 2a, 2e, 3a, 3e and 5b exhibited the most significant anti-inflammatory and immunomodulatory activities. Hence, these were evaluated for in vivo acute gastric ulcerogenicity. The compounds were safe to gastric mucosa, probably due to masking of the free -COOH group of IB and MES, and/or to the BZ nucleus itself. A benzoyl group at 5-position of BZ and ABZ incurred maximum immunostimulatory activity. In contrast, a -NO2 group incurred the maximum immunosuppressive action. Docking analysis revealed the compounds to be more selective towards COX-2 enzyme, which support the gastroprotective activity. These results suggest that the compounds can be taken as lead for development of new drugs for the treatment of immune related inflammatory disorders, such as cancer and rheumatoid arthritis.

  2. Comparison of efficacy of multimatrix mesalazine 4.8 g/day once-daily with other high-dose mesalazine in active ulcerative colitis: a randomized, double-blind study.

    Science.gov (United States)

    Ogata, Haruhiko; Aoyama, Nobuo; Mizushima, Seiichi; Hagino, Atsushi; Hibi, Toshifumi

    2017-07-01

    This study assessed the efficacy and safety of high-dose multimatrix mesalazine once-daily (QD) compared to another form of high-dose mesalazine. In this multicenter, randomized, double-blind study, 280 patients with mildly to moderately active ulcerative colitis (UC) received multimatrix mesalazine 4.8 g/day QD or pH-dependent-release mesalazine 3.6 g/day three times daily for 8 weeks. The primary endpoint was the change in the UC-Disease Activity Index (UC-DAI) at the end of the treatment period. The change in the UC-DAI (mean±standard deviation) in the per-protocol set was -2.6±2.47 in the multimatrix mesalazine 4.8 g/day group (n=134) and -1.8±2.64 in the pH-dependent-release mesalazine 3.6 g/day group (n=129). The difference in the mean change between the 2 groups was -0.7 (two-sided 95% confidence interval, -1.3 to -0.1). The noninferiority of multimatrix mesalazine 4.8 g/day to pH-dependent-release mesalazine 3.6 g/day was verified within the noninferiority margin (1.1). The superiority of multimatrix mesalazine 4.8 g/day to pH-dependent-release mesalazine 3.6 g/day was also investigated and confirmed in the full analysis set, according to the study protocol. In subgroup analyses, the effectiveness of multimatrix mesalazine 4.8 g/day was consistent in all subgroups. There was no difference in safety between the 2 treatment groups. Multimatrix mesalazine 4.8 g/day has higher efficacy and shows no difference in safety in mildly to moderately active UC, in comparison with pH-dependent-release mesalazine 3.6 g/day.

  3. Safety and Effectiveness of Once-Daily Tadalafil (5 mg) Therapy in Korean Men with Benign Prostatic Hyperplasia/Lower Urinary Tract Symptoms in a Real-World Clinical Setting: Results from a Post-Marketing Surveillance Study.

    Science.gov (United States)

    Won, Ji Eon; Chu, Ji Yeon; Choi, Hyunah Caroline; Chen, Yun; Park, Hyun Jun; Dueñas, Héctor José

    2017-09-06

    The aim of this study was to investigate the safety and effectiveness of tadalafil 5 mg once daily (quaque die [everyday], QD) among Korean men with benign prostatic hyperplasia (BPH)/lower urinary tract symptoms (LUTS) in a real-world clinical setting. This was a single-country, prospective, observational cohort study in which patients newly prescribed tadalafil 5 mg QD for the treatment of BPH/LUTS were followed-up for 12±2 or 24±2 weeks, or to the last treatment, during post-marketing surveillance. Safety was evaluated in terms of the frequency of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). Effectiveness was assessed by changes in the International Prostate Symptom Score (IPSS) from baseline to each endpoint. All patients receiving ≥1 dose of tadalafil 5 mg QD (N=637) were included in the safety population. Two percent of patients (n=13) experienced 15 TEAEs of mild (n=10; 66.7%) or moderate (n=5; 33.3%) severity. No severe TEAEs and no SAEs were reported. Effectiveness evaluations included all patients receiving tadalafil who had both baseline and endpoint observations (12-week, N=265; 24-week, N=44). Compared with baseline, mean the IPSS total score (±standard error) significantly improved by 4.7±0.3 and 6.4±0.7 points at the 12- and 24-week endpoints, respectively (p<0.0001), with significant improvements also observed on the storage, voiding, and quality of life subscores. In total, 69.1% of the patients had a clinically meaningful ≥3-point improvement in the IPSS total score. Tadalafil 5 mg QD was well tolerated and effective in Korean men with BPH/LUTS in a real-world clinical setting.

  4. The effects of lumiracoxib 100 mg once daily vs. ibuprofen 600 mg three times daily on the blood pressure profiles of hypertensive osteoarthritis patients taking different classes of antihypertensive agents

    Science.gov (United States)

    MacDonald, T M; Richard, D; Lheritier, K; Krammer, G

    2010-01-01

    Aims: To examine whether the blood pressure (BP) profiles of lumiracoxib and high-dose ibuprofen differed in patients treated with different classes of antihypertensive medications. Methods: A 4-week, multicentre, randomised, double-blind study has compared the effects of lumiracoxib 100 mg once daily (od) (n = 394) and ibuprofen 600 mg three times daily (tid) (n = 393) on ambulatory BP in osteoarthritis (OA) patients with controlled hypertension. Here, we present subgroup analyses for patients receiving different antihypertensive classes. The primary outcome was a comparison of the change in 24-h mean systolic ambulatory BP (MSABP) from baseline to week 4. Patients receiving angiotensin receptor blockers (ARBs) or angiotensin-converting enzyme inhibitors (ACEIs) represented the largest subgroups receiving antihypertensive monotherapy. Results: For patients receiving an ARB monotherapy, the least squares mean (LSM) 24-h MSABP at week 4 fell with lumiracoxib 100 mg od and increased with ibuprofen 600 mg tid, creating an estimated treatment difference of 8.1 mmHg in favour of lumiracoxib (p treatment difference was 8.2 mmHg (p treatment differences were greater than observed in the overall population (5.0 mmHg in favour of lumiracoxib). In patients receiving diuretics or calcium channel blockers, treatment differences in MSABP were smaller and not statistically significant, although they remained in favour of lumiracoxib. Conclusion: Lumiracoxib 100 mg od resulted in less destabilisation of BP than high-dose ibuprofen 600 mg tid, and this effect was the greatest in subgroups treated with drugs blocking the renin-angiotensin system. PMID:20518950

  5. Efficacy and safety of a once-daily extended-release formulation of pramipexole switched from an immediate-release formulation in patients with advanced Parkinson's disease: results from an open-label study.

    Science.gov (United States)

    Takanashi, M; Shimo, Y; Hatano, T; Oyama, G; Hattori, N

    2013-12-01

    This study aimed to evaluate the efficacy and safety of an extended-release tablet formulation of pramipexole (PPX-ER) given once daily when switched from an immediate-release tablet formulation (PPX-IR) given 3 times daily. This open-label study included 29 patients with idiopathic Parkinson's disease (PD) who were followed for 8 weeks. Primary endpoints were Unified Parkinson's Disease Rating Scale (UPDRS) part III score, a physician evaluation of motor symptoms; nocturnal and early morning symptoms (NEMS) score, based on the results for 4 items in the Parkinson's Disease Sleep Scale and the Movement Disorder Society - sponsored revision of the UPDRS; and patients' formulation preference, determined through questionnaires. Secondary endpoints were nocturnal sleep disturbance, evaluated using the revised version of the Parkinson's Disease Sleep Scale (PDSS-2); quality of life, evaluated using the 39-item Parkinson's Disease Questionnaire (PDQ-39); Clinical Global Impression-Improvement (CGI-I) score; Patient Global Impression-Improvement (PGI-I) score; and caregiver formulation preference. UPDRS part III score (mean ± SD) was significantly decreased after 4 weeks (13.9 ± 7.3; P=0.030) and 8 weeks (12.2 ± 7.3; P<0.001) from baseline (15.3 ± 7.0). However, no significant change was found in NEMS scale, PDSS-2 or PDQ-39 scores. After 8 weeks, the responder rates based on CGI-I and PGI-I scores were 27.6% and 20.7%, respectively. As a result of the questionnaire, 63.0% of patients and 58.8% of their caregivers preferred PPX-ER. A non-serious drug-related adverse event (diarrhea) was observed in one patient. In conclusion, PPX-ER can be considered as a useful treatment option when PPX-IR needs to be switched to other dopamine agonists.This study is registered with UMIN-CTR (UMIN000006521).

  6. Update on the role of modified release mesalamine in the management of ulcerative colitis and Crohn’s disease

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    Glen A Doherty

    2009-12-01

    Full Text Available Glen A Doherty, Mark A PeppercornCenter for Inflammatory Bowel Disease, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston MA, USAAbstract: 5-aminosalicyclates (5-ASA remain a key first-line therapy for patients with ulcerative colitis (UC. A range of 5-ASA preparations is available and Eudragit-S® coated modified release formulations of mesalamine, such as Asacol®, remain among the most popular choices. We here review the current understanding of the mechanism of action of 5-ASA in inflammatory bowel disease. We evaluate evidence supporting the efficacy and safety of modified release mesalamine for both induction and remission maintenance in UC, including a review of the data from the recent ASCEND studies. We also examine the controversial issue of the role of mesalamine in treatment of Crohn’s disease (CD and highlight data supporting its use following surgically induced remission of CD. Evidence supporting the use of mesalamine as prophylaxis for colorectal cancer and dysplasia will be considered. Finally, recent developments in our understanding of how to use modified release mesalamine in a safe and cost-effective manner are evaluated, including discussion of the importance of studying patient non-adherence as a key component of future studies in this area.Keywords: mesalamine (mesalazine, 5-aminosalicyclate, ulcerative colitis, Crohn’s disease, modified release

  7. Preparation and evaluation of mesalamine collagen in situ rectal gel: a novel therapeutic approach for treating ulcerative colitis.

    Science.gov (United States)

    Ramadass, Satiesh Kumar; Perumal, Sathiamurthi; Jabaris, Sugin Lal; Madhan, Balaraman

    2013-01-23

    Ulcerative colitis (UC) is a chronic inflammatory disease that primarily affects the colonic mucosa. Mesalamine had been established as a first line drug for treating mild to moderate UC. A continued availability of the drug for treatment of damaged tissues remains a great challenge today. In the present study, a novel mesalamine collagen in situ gel has been prepared using type I collagen, which is pH/temperature sensitive. This hydrogel undergoes sol-gel transition under physiological pH and temperature which was confirmed by rheological studies. The in vitro release profile demonstrated sustained release of mesalamine over a period of 12h. The in vivo efficacy of the in situ gel was performed using dextran sodium sulphate induced ulcerative colitis model in BALB/c mice. The clinical parameters such as, body weight changes, rectal bleeding and stool consistency were evaluated. In addition, the histopathological investigation was conducted to assess severity of mucosal damage and inflammation infiltrate. There was a significant reduction in rectal bleeding and mucosal damage score for collagen-mesalamine in situ gel group compared to the reference group. Apart from releasing mesalamine in controlled manner, the strategy of administering mesalamine through collagen in situ gel facilitates regeneration of damaged mucosa resulting in a synergistic effect for the treatment of ulcerative colitis.

  8. Randomised study to assess the efficacy and safety of once-daily etravirine-based regimen as a switching strategy in HIV-infected patients receiving a protease inhibitor-containing regimen. Etraswitch study.

    Directory of Open Access Journals (Sweden)

    Patricia Echeverría

    Full Text Available BACKGROUND: Etravirine (ETR was approved for patients with virological failure and antiretroviral resistance mutations. It has also shown antiviral efficacy in antiretroviral-naïve patients. However, data on the switching from protease inhibitors (PI to ETR are lacking. METHODS: HIV-1-infected patients with suppressed viral load (VL during a PI-containing regimen (>12 months and no previous virological failure were randomized to switch from the PI to ETR (400 mg/day, dissolved in water (ETR group, n = 22 or to continue with the same regimen (control group, n = 21. Percentage of patients with VL ≤ 50 copies/mL were assessed at week 48, as well as changes in CD4 T-cell counts and metabolic profile. RESULTS: We included 43 patients [72.9% male, 46.3 (42.2; 50.6 years]. Two patients receiving ETR (grade-1 diarrhea and voluntary discontinuation and another in the control group (simplification discontinued therapy early. No patients presented virological failure (two consecutive VL>50 copies/mL; treatment was successful in 95.2% of the control group and 90.9% of the ETR group (intention-to-treat analysis, missing = failure (p = 0.58. CD4+ T-cell counts did not significantly vary [+49 cells/µL in the ETR group (p = 0.25 and -4 cells/µL in the control group (p = 0.71]. The ETR group showed significant reductions in cholesterol (p<0.001, triglycerides (p = <0.001, and glycemia (p = 0.03 and higher satisfaction (0-10 scale (p = 0.04. Trough plasma concentrations of ETR were similar to observed in studies using ETR twice daily. CONCLUSION: Switch from a PI-based regimen to a once-daily combination based on ETR maintained undetectable VL during 48 weeks in virologically suppressed HIV-infected patients while lipid profile and patient satisfaction improved significantly. TRIAL REGISTRATION: ClinicalTrials.gov NCT01034917.

  9. Bronchodilator efficacy of 18 µg once-daily tiotropium inhalation via Discair® versus HandiHaler® in adults with chronic obstructive pulmonary disease: randomized, active-controlled, parallel-group, open-label, Phase IV trial

    Directory of Open Access Journals (Sweden)

    Yildiz P

    2016-11-01

    Full Text Available Pinar Yildiz, Mesut Bayraktaroglu, Didem Gorgun, Funda Secik Clinics of Chest Diseases, Yedikule Chest Diseases and Thoracic Surgery Training and Research Hospital, Istanbul, Turkey Purpose: To compare the bronchodilator efficacy of 18 µg once-daily tiotropium inhalation administered via Discair® versus HandiHaler® in adults with moderate-to-severe chronic obstructive pulmonary disease (COPD.Patients and methods: Fifty-eight patients with moderate-to-severe COPD were enrolled in this randomized, active-controlled, parallel-group, open-label, Phase IV non-inferiority trial. Patients were randomly assigned to a test group (n=29, inhalation with Discair or a reference group (n=29, inhalation with HandiHaler. The primary efficacy parameter was the average maximum change in forced expiratory volume in 1 second (FEV1, in L. Change in forced vital capacity (FVC, in L, %FEV1 and %FVC, the standardized area under the response–time curve (AUC for the absolute change in FEV1 and FVC, time to onset and peak of response, and safety data were also evaluated.Results: The test inhaler was non-inferior to the reference inhaler in terms of maximum change in FEV1 at 24 h (unadjusted change: 0.0017 L [95% confidence interval [CI]: –0.0777, 0.0812]; change adjusted for time to reach maximum change in FEV1 and smoking in pack-years: 0.0116 L [95% CI: –0.0699, 0.0931], based on a non-inferiority margin of 0.100 L. There were also no significant differences between the two groups in maximum change in FVC value from baseline (0.3417 L vs 0.4438 L, P=0.113, percent change from baseline (22.235 vs 20.783 for FEV1, P=0.662; 16.719 vs 20.337 for FVC, P=0.257, and AUC0–24 h (2.949 vs 2.833 L for FEV1, P=0.891; 2.897 vs 4.729 L for FVC, P=0.178. There were no adverse events, serious adverse events, or deaths.Conclusion: Our findings show that the Discair was non-inferior to the HandiHaler. More specifically, these devices had similar clinical efficacy in terms of

  10. Trough-to-peak ratio, smoothness index, and circadian blood pressure profile after treatment with once-daily fixed combination of losartan 100 and hydrochlorothiazide 25 in essential hypertension.

    Science.gov (United States)

    Coca, Antonio; Sobrino, Javier; Soler, Josep; Felip, Angela; Pelegrí, Antoni; Mínguez, Agustin; Vila, Joaquim; de la Sierra, Alejandro; Plana, Jaume

    2002-06-01

    The once-daily fixed combination of losartan 100 mg/hydrochlorothiazide 25 mg was evaluated for safety and efficacy in a multicenter open study by using 24-h ambulatory blood pressure monitoring in untreated patients with moderate-to-severe essential hypertension or patients with uncontrolled hypertension despite treatment with monotherapy or low-dose combination. After a 2-week washout period, 41 patients (22 men, 19 women) aged 34-74 years, showing a mean daytime blood pressure > 135/85 mm Hg, were treated with losartan 100 mg/hydrochlorothiazide 25 for 8 weeks. Ambulatory blood pressure was monitored at the end of the washout period and during the last week of treatment. A significant reduction in the average values of clinic blood pressure (from 169.9 +/- 13.5 mm Hg to 139.5 +/- 15.6 mm Hg, p SBP]; and from 102.2 +/- 7.1 mm Hg to 85.1 +/- 9.5 mm Hg, p SBP and 24-h DBP were significantly reduced (from 145.7 +/- 13.1 mm Hg to 128.3 +/- 14.6 mm Hg, p SBP; and from 90.3 +/- 7.3 mm Hg to 79.2 +/- 8.6 mm Hg, p SBP and 12.1 +/- 7.4 mm Hg for 24-h DBP, whereas the lowering at trough was 17.8 +/- 12.0 mm Hg and 10.4 +/- 8.1 mm Hg, respectively. The trough-to-peak ratio (T/P) was 0.88 for SBP and 0.86 for DBP, and the smoothness index was 7.36 for SBP and 6.37 for DBP. The response rate was 87.8% (blood pressure lowering > 5 mm Hg of either 24-h SBP or 24-h DBP average values). Among responders, T/P ratio was 0.89 for SBP and 0.87 for DBP, and the smoothness index was 8.09 for SBP and 7.15 for DBP. No side effects or changes in metabolic parameters were observed. The fixed combination of losartan 100 mg/hydrochlorothiazide 25 was very effective and well tolerated.

  11. Impact of HIV subtype on response and resistance in antiretroviral-naïve adults comparing treatment with once daily versus twice daily ritonavir boosted fosamprenavir in combination with Abacavir/Lamivudine

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    Lisa L. Ross

    2011-12-01

    Full Text Available The impact of HIV-1 subtype on resistance mutation selection and on virologic response to fosamprenavir in combination with once-daily (QD versus twice-daily (BID dosing of ritonavir was examined in a prospective, open label, randomized study in antiretroviral-naïve, HIV-1 infected subjects. We studied APV109141 compared QD fosamprenavir/ritonavir (1400mg/100mg to BID fosamprenavir/ritonavir (700mg/100mg, administered in combination with a QD fixed-dose abacavir/lamivudine (600 mg/300 mg combination tablet through 48 weeks in ART-naïve subjects. HIV genotypes were obtained from all subjects at screen. Subjects with virologic failure (VF were also genotyped at baseline and VF. HIV subtypes observed in the ITT (n=214 population were A or AE or AG circulating recombinant forms (CRFs 19%; B 62%; BF or BG CRFs 2%; C or CPX CRFs 7%; D 2%; F1 7%; G <1%. By TLOVR (ITT-exposed, 86/106 (81% of subjects on QD study arm and 87/106 (82% in the BID arm achieved plasma HIV-RNA<400 copies/mL at Week 48. Three subjects met VF criteria, 2 receiving QD fosamprenavir/ritonavir; 1 receiving BID fosamprenavir/ritonavir; (HIV subtype B, F1 A1, respectively. Baseline drug resistance was detected in 2/3 VFs: Subject 1-RT: K103K/N, T215C; major PI: V82A, L90M; and Subject 2-RT: M41L, L74V. Only virus from one subject with VF selected for any treatment-emergent mutation (Subject 1; M184V. Post-VF, Subject 3 (subtypeA1 suppressed HIV-RNA >400 copies/mL through 48 weeks. Subtype appeared to have no preferential impact on virologic response or selection for specific resistance mutations in subjects receiving fosamprenavir/ritonavir. Virologic failure rate was rare (3 subjects; each from different subtypes. At VF, virus from only one subject selected any HIV NRTI mutation (M184V; none selected major protease mutations.

  12. Long-term retention on treatment with lumiracoxib 100 mg once or twice daily compared with celecoxib 200 mg once daily: A randomised controlled trial in patients with osteoarthritis

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    Notter Marianne

    2008-03-01

    Full Text Available Abstract Background The efficacy, safety and tolerability of lumiracoxib, a novel selective cyclooxygenase-2 (COX-2 inhibitor, has been demonstrated in previous studies of patients with osteoarthritis (OA. As it is important to establish the long-term safety and efficacy of treatments for a chronic disease such as OA, the present study compared the effects of lumiracoxib at doses of 100 mg once daily (o.d. and 100 mg twice daily (b.i.d. with those of celecoxib 200 mg o.d. on retention on treatment over 1 year. Methods In this 52-week, multicentre, randomised, double-blind, parallel-group study, male and female patients (aged at least 40 years with symptomatic primary OA of the hip, knee, hand or spine were randomised (1:2:1 to lumiracoxib 100 mg o.d. (n = 755, lumiracoxib 100 mg b.i.d. (n = 1,519 or celecoxib 200 mg o.d. (n = 758. The primary objective of the study was to demonstrate non-inferiority of lumiracoxib at either dose compared with celecoxib 200 mg o.d. with respect to the 1-year retention on treatment rate. Secondary outcome variables included OA pain in the target joint, patient's and physician's global assessments of disease activity, Short Arthritis assessment Scale (SAS total score, rescue medication use, and safety and tolerability. Results Retention rates at 1 year were similar for the lumiracoxib 100 mg o.d., lumiracoxib 100 mg b.i.d. and celecoxib 200 mg o.d. groups (46.9% vs 47.5% vs 45.3%, respectively. It was demonstrated that retention on treatment with lumiracoxib at either dose was non-inferior to celecoxib 200 mg o.d. Similarly, Kaplan-Meier curves for the probability of premature discontinuation from the study for any reason were similar across the treatment groups. All three treatments generally yielded comparable results for the secondary efficacy variables and all treatments were well tolerated. Conclusion Long-term treatment with lumiracoxib 100 mg o.d., the recommended dose for OA, was as effective and well

  13. A pharmacokinetic comparison of single doses of once-daily cyclobenzaprine extended-release 15 mg and 30 mg: a randomized, double-blind, two-period crossover study in healthy volunteers.

    Science.gov (United States)

    Darwish, Mona; Chang, Steven; Hellriegel, Edward T

    2009-01-01

    The purpose of this study was to compare the pharmacokinetics and tolerability of single oral doses of cyclobenzaprine extended-release (CER) 15- and 30-mg capsules. This was a randomized, double-blind, 2-period crossover study in healthy adults aged 18 to 40 years. Subjects were assigned to receive a single dose of either CER 15 mg or 30 mg on days 1 and 15, separated by a 14-day washout. Study comparisons included the plasma cyclobenzaprine AUC to 168 hours after dosing (AUC(0-168)), AUC(0-infinity), and C(max). Plasma cyclobenzaprine T(max), terminal elimination t(1/2), and adverse events (AEs) were also assessed. Sixteen subjects (9 women, 7 men) were randomized to receive cyclobenzaprine 15 mg or 30 mg; 13 (81.3%) were white and 3 (18.8%) were black. Mean age and weight were 30.2 years and 70.7 kg, respectively. The shapes of the pharmacokinetic profiles for CER 15 and 30 mg were parallel. Mean observed values for dose-dependent pharmacokinetic parameters of CER 15 and 30 mg were as follows: AUC(0-168), 318.3 and 736.6 ng . h/mL, respectively; AUC(0-infinity)), 354.1 and 779.9 ng . h/mL; and C(max), 8.3 and 19.9 ng/mL. Dose-independent parameters were comparable across doses. Median observed Tmax was 6.0 hours for both CER doses; mean t(1/2) was 33.4 hours for CER 15 mg and 32.0 hours for CER 30 mg. The bioavailability of the 2 doses, as indicated by the least squares mean AUC(0-infinity), was 330.3 ng . h/mL for CER 15 mg and 755.1 ng . h/mL for CER 30 mg. During the CER 15-mg treatment sequence, 5 subjects experienced 5 AEs (headache, dizziness, musculoskeletal pain, dermatitis, and glossodynia); during the CER 30-mg treatment sequence, 2 subjects experienced 2 AEs (somnolence and dysmenorrhea). All AEs were mild in intensity. No serious AEs occurred during the study. Once-daily CER 15 and 30 mg exhibited similarly shaped pharmacokinetic profiles. AUC(0-168), AUC(0-infinity)), and C(max) values for the 30-mg dose were approximately double those for the 15-mg

  14. Posterior reversible encephalopathy syndrome with PLEDs-plus due to mesalamine

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    Ajith Cherian

    2014-01-01

    Full Text Available A 32-year-old lady developed status epilepticus and acute visual loss while on mesalamine for Crohn′s disease. Her clinical course and magnetic resonance imaging (MRI were suggestive of posterior reversible encephalopathy syndrome (PRES. She had periodic lateralized epileptiform discharges plus (PLEDs-plus on electroencephalogram (EEG, which responded to sodium valproate. Her vision improved from counting fingers at one-meter distance to 6/12. Though different cytotoxic drugs have been implicated as causative agents, this is the first case report of mesalamine-induced PRES. This case highlights the need for aggressive treatment of PLEDs-plus with EEG monitoring using a broad-spectrum antiepileptic drug like valproate, which has contributed to the rapid reversibility of vision in PRES subjects, and the need for a thorough drug history for etiological clues.

  15. A novel pH–enzyme-dependent mesalamine colon-specific delivery system

    OpenAIRE

    Jin L; Ding Y; Zhang Y; Xu X; Cao Q

    2016-01-01

    Lei Jin, Yi-cun Ding, Yu Zhang, Xiao-qing Xu, Qin Cao Department of Gastroenterology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China Abstract: The aim of the present study was to design a new pH–enzyme double-dependent mesalamine colon-specific delivery system. The drug release behaviors in vitro and pharmacokinetics and biodistribution in vivo were further evaluated. The mean particle diameters of mesal...

  16. Improved glycemic control with no weight increase in patients with type 2 diabetes after once-daily treatment with the long-acting glucagon-like peptide 1 analog liraglutide (NN2211): a 12-week, double-blind, randomized, controlled trial

    DEFF Research Database (Denmark)

    Madsbad, Sten; Schmitz, Ole; Ranstam, Jonas;

    2004-01-01

    OBJECTIVE: Liraglutide is a long-acting glucagon-like peptide 1 analog designed for once daily injection. This study assessed the efficacy and safety of liraglutide after 12 weeks of treatment in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: A double-blind, randomized, parallel...

  17. Improved glycemic control with no weight increase in patients with type 2 diabetes after once-daily treatment with the long-acting glucagon-like peptide 1 analog liraglutide (NN2211): a 12-week, double-blind, randomized, controlled trial

    DEFF Research Database (Denmark)

    Madsbad, Sten; Schmitz, Ole; Ranstam, Jonas

    2004-01-01

    OBJECTIVE: Liraglutide is a long-acting glucagon-like peptide 1 analog designed for once daily injection. This study assessed the efficacy and safety of liraglutide after 12 weeks of treatment in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: A double-blind, randomized, parallel...

  18. Diatom silica microparticles for sustained release and permeation enhancement following oral delivery of prednisone and mesalamine.

    Science.gov (United States)

    Zhang, Hongbo; Shahbazi, Mohammad-Ali; Mäkilä, Ermei M; da Silva, Tiago H; Reis, Rui L; Salonen, Jarno J; Hirvonen, Jouni T; Santos, Hélder A

    2013-12-01

    Diatoms are porous silica-based materials obtained from single cell photosynthetic algae. Despite low cost, easy purification process, environmentally safe properties, and rapidly increasing potentials for medical applications, the cytotoxicity of diatoms and the effect on drug permeation of oral formulations have not been studied so far. Herein, we have evaluated the potential of diatom silica microparticles (DSMs) for the delivery of mesalamine and prednisone, which are two commonly prescribed drugs for gastrointestinal (GI) diseases. Transmission electron microscopy analysis of the morphological surface changes of Caco-2/HT-29 monolayers and the cell viability data in colon cancer cells (Caco-2, HT-29 and HCT-116) showed very low toxicity of diatoms at concentrations up to 1000 μg/mL. The mesalamine and prednisone release under simulated GI conditions indicated prolonged release of both drugs from the diatoms. Furthermore, drug permeation across Caco-2/HT-29 co-culture monolayers demonstrated that diatoms are capable to enhance the drug permeability. Overall, this study evaluated DSMs' cytotoxicity in colon cancer cells and the effect of DSMs on drug permeability across Caco-2/HT-29 monolayers. Our results demonstrate that DSMs can be considered as a non-cytotoxic biomaterial with high potential to improve the mesalamine and prednisone bioavailability by sustaining the drug release and enhancing drug permeability.

  19. A crossover-crossback prospective study of dibutyl-phthalate exposure from mesalamine medications and semen quality in men with inflammatory bowel disease

    DEFF Research Database (Denmark)

    Nassan, Feiby L; Coull, Brent A; Skakkebaek, Niels E

    2016-01-01

    BACKGROUND: Phthalates are widely used chemicals with ubiquitous exposure. Dibutyl-phthalate (DBP), a male reproductive toxicant in animals, is understudied in humans. Some mesalamine medications used to treat inflammatory bowel disease (IBD) have DBP in their coating, whereas other mesalamine fo...

  20. Efficacy and safety of rivaroxaban compared with warfarin among elderly patients with nonvalvular atrial fibrillation in the Rivaroxaban Once Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF)

    DEFF Research Database (Denmark)

    Halperin, Jonathan L; Hankey, Graeme J; Wojdyla, Daniel M;

    2014-01-01

    BACKGROUND: Nonvalvular atrial fibrillation is common in elderly patients, who face an elevated risk of stroke but difficulty sustaining warfarin treatment. The oral factor Xa inhibitor rivaroxaban was noninferior to warfarin in the Rivaroxaban Once Daily, Oral, Direct Factor Xa Inhibition Compar...... younger patients, but the efficacy and safety of rivaroxaban relative to warfarin did not differ with age, supporting rivaroxaban as an alternative for the elderly....

  1. Mesalamine modulates intercellular adhesion through inhibition of p-21 activated kinase-1.

    Science.gov (United States)

    Khare, Vineeta; Lyakhovich, Alex; Dammann, Kyle; Lang, Michaela; Borgmann, Melanie; Tichy, Boris; Pospisilova, Sarka; Luciani, Gloria; Campregher, Christoph; Evstatiev, Rayko; Pflueger, Maren; Hundsberger, Harald; Gasche, Christoph

    2013-01-15

    Mesalamine (5-ASA) is widely used for the treatment of ulcerative colitis, a remitting condition characterized by chronic inflammation of the colon. Knowledge about the molecular and cellular targets of 5-ASA is limited and a clear understanding of its activity in intestinal homeostasis and interference with neoplastic progression is lacking. We sought to identify molecular pathways interfered by 5-ASA, using CRC cell lines with different genetic background. Microarray was performed for gene expression profile of 5-ASA-treated and untreated cells (HCT116 and HT29). Filtering and analysis of data identified three oncogenic pathways interfered by 5-ASA: MAPK/ERK pathway, cell adhesion and β-catenin/Wnt signaling. PAK1 emerged as a consensus target of 5-ASA, orchestrating these pathways. We further investigated the effect of 5-ASA on cell adhesion. 5-ASA increased cell adhesion which was measured by cell adhesion assay and transcellular-resistance measurement. Moreover, 5-ASA treatment restored membranous expression of adhesion molecules E-cadherin and β-catenin. Role of PAK1 as a mediator of mesalamine activity was validated in vitro and in vivo. Inhibition of PAK1 by RNA interference also increased cell adhesion. PAK1 expression was elevated in APC(min) polyps and 5-ASA treatment reduced its expression. Our data demonstrates novel pharmacological mechanism of mesalamine in modulation of cell adhesion and role of PAK1 in APC(min) polyposis. We propose that inhibition of PAK1 expression by 5-ASA can impede with neoplastic progression in colorectal carcinogenesis. The mechanism of PAK1 inhibition and induction of membranous translocation of adhesion proteins by 5-ASA might be independent of its known anti-inflammatory action.

  2. Rectal budesonide and mesalamine formulations in active ulcerative proctosigmoiditis: efficacy, tolerance, and treatment approach

    Directory of Open Access Journals (Sweden)

    Christophi GP

    2016-05-01

    Full Text Available George P Christophi, Arvind Rengarajan, Matthew A Ciorba Division of Gastroenterology, Washington University School of Medicine, St. Louis, MO, USA Abstract: Ulcerative colitis (UC is an immune-mediated disease of the colon that is characterized by diffuse and continuous inflammation contiguous from the rectum. Half of UC patients have inflammation limited to the distal colon (proctitis or proctosigmoiditis that primarily causes symptoms of bloody diarrhea and urgency. Mild-to-moderate distal UC can be effectively treated with topical formulations (rectal suppositories, enemas, or foam of mesalamine or steroids to reduce mucosal inflammation and alleviate symptoms. Enemas or foam formulations adequately reach up to the splenic flexure, have a minimal side-effect ­profile, and induce remission alone or in combination with systemic immunosuppressive therapy. Herein, we compare the efficacy, cost, patient tolerance, and side-effect profiles of steroid and mesalamine rectal formulations in distal UC. Patients with distal mild-to-moderate UC have a remission rate of approximately 75% (NNT =2 after treatment for 6 weeks with mesalamine enemas. Rectal budesonide foam induces remission in 41.2% of patients with mild-to-moderate active distal UC compared to 24% of patient treated with placebo (NNT =5. However, rectal budesonide has better patient tolerance profile compared to enema formulations. Despite its favorable efficacy, safety, and cost profiles, patients and physicians significantly underuse topical treatments for treating distal colitis. This necessitates improved patient education and physician familiarity regarding the indications, effectiveness, and potential financial and tolerability barriers in using rectal formulations. Keywords: inflammatory bowel disease, treatment cost effectiveness, Crohn’s disease, ulcerative colitis, colon mucosa, proctitis suppositories, topical immunosuppressive therapy

  3. Mesalamine hypersensitivity and Kounis syndrome in a pediatric ulcerative colitis patient

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    5-aminosalicylic acid (mesalamine) rarely induces hyper-sensitivity reactions. If chest pain associated with atypical electrocardiographic changes are seen during its adminis-tration, one should always bear in mind type I variant of Kounis syndrome. This variant includes patients, of any age, with normal coronary arteries, without predisposing factors for coronary artery disease, in whom the acute release of inflammatory mediators from mast cells can induce either sudden coronary artery narrowing, without increase of cardiac enzymes and troponins, or coronary artery spasm that progresses to acute myocardial infarc-tion, with elevated cardiac enzymes and troponins.

  4. Fabrication of an electrochemical sensor based on computationally designed molecularly imprinted polymer for the determination of mesalamine in real samples

    Energy Technology Data Exchange (ETDEWEB)

    Torkashvand, M. [Department of Analytical Chemistry, Razi University, Kermanshah (Iran, Islamic Republic of); Gholivand, M.B., E-mail: mbgholivand@yahoo.com [Department of Analytical Chemistry, Razi University, Kermanshah (Iran, Islamic Republic of); Taherkhani, F. [Department of Physical Chemistry, Razi University, Kermanshah (Iran, Islamic Republic of)

    2015-10-01

    A novel electrochemical sensor based on mesalamine molecularly imprinted polymer (MIP) film on a glassy carbon electrode was fabricated. Density functional theory (DFT) in gas and solution phases was developed to study the intermolecular interactions in the pre-polymerization mixture and to find the suitable functional monomers in MIP preparation. On the basis of computational results, o-phenylenediamine (OP), gallic acid (GA) and p-aminobenzoic acid (ABA) were selected as functional monomers. The MIP film was cast on glassy carbon electrode by electropolymerization of solution containing ternary monomers and then followed by Ag dendrites (AgDs) with nanobranch deposition. The surface feature of the modified electrode (AgDs/MIP/GCE) was characterized by scanning electron microscopy (SEM) and electrochemical impedance spectroscopy (EIS). Under the optimal experimental conditions, the peak current was proportional to the concentration of mesalamine ranging from 0.05 to 100 μM, with the detection limit of 0.015 μM. The proposed sensor was applied successfully for mesalamine determination in real samples. - Highlights: • The determination of MES using AgDs/MIP/GCE is reported for the first time. • The computer assisted design of terpolymer MIPs was used to screen monomers. • Theoretical results of DFT approach were in agreement with experimental results. • The sensor displayed a high selectivity for template in the presence of interferes. • The developed sensor has been applied to determine mesalamine in real samples.

  5. DEVELOPMENT AND VALIDATION OF A STABILITY INDICATING ASSAY METHOD OF MESALAMINE BY USING DIFFERENT STRESS DEGRADATION CONDITIONS

    Directory of Open Access Journals (Sweden)

    S. H. Gatkal*, P. R. Mhatre, V. V. Chopade and P. D. Chaudhari

    2013-01-01

    Full Text Available A simple, sensitive, highly accurate UV spectrophotometric method has been developed for the determination of mesalamine in bulk and tablet dosage form. Solution of mesalamine in distilled water shows maximum absorbance at 330 nm. Beer’s law was obeyed in the concentration range of 2-16 μg/ml with the slope, intercept, correlation coefficient, detection and quantitation limits were also calculated. The proposed method has been applied successfully for the analysis of the drug in pure and in its tablets dosage forms. Result of percentage recovery and placebo interference shows that the method was not affected by the presence of common excipients. The method was validated by determining its sensitivity, accuracy and precision which proves suitability of the developed method for the routine estimation of mesalamine in bulk and solid dosage form. The method was then validated for different parameters as per the ICH (International Conference for Harmonization guidelines. Mesalamine was subjected to stress degradation under different conditions recommended by ICH. The samples generated were used for degradation studies using the developed method.

  6. N-acetyl-L-cysteine combined with mesalamine in the treatment of ulcerative colitis: Randomized, placebo-controlled pilot study

    Institute of Scientific and Technical Information of China (English)

    Luis G Guijarro; David Prieto-Merino; Venancio Gonzalez Lara; Amado Salvador Pe(n)a; Jose Mate; Javier P Gisbert; Jose Luis Perez-Calle; Ignacio Marín-Jimenez; Encarna Arriaza; Tomás Olleros; Maria Delgado; Maria S Castillejo

    2008-01-01

    AIM: To evaluate the effectiveness and safety of oral N-acetyI-L-cysteine (NAC) co-administration with mesalamine in ulcerative colitis (UC) patients.METHODS: Thirty seven patients with mild to moderate UC were randomized to receive a fourowk course of oral mesalamine (2.4 g/d) plus N-acetyI-L-cysteine (0.8 g/d)(group A) or mesalamine plus placebo (group B).Patients were monitored using the Modified TrueloveWitts Severity Index (MIWSI). The primary endpoint was clinical remission (MIWSI ≤ 2) at 4 wk. Secondary endpoints were clinical response (defined as a reduction from baseline in the MIWSI of≥ 2 points) and drug safety. The serum TNF-α, interleukin-6, interleukin-8 and MCP-1 were evaluated at baseline and at 4 wk of treatment.RESULTS: Analysis per-protocol criteria showed clinical remission rates of 63% and 50% after 4 wk treatment with mesalamine plus N-acetyI-L-cysteine (group A) and mesalamine plus placebo (group 13) respectively (OR = 1.71;95% CI: 0.46 to 6.36; P = 0.19; NNT = 7.7). Analysis of variance (ANOVA) of data indicated a significant reduction of MIWSI in group A (P = 0.046) with respect to basal condition without significant changes in the group B (P = 0.735) during treatment. Clinical responses were 66% (group A) vs 44% (group B) alter 4 wk of treatment (OR = 2.5; 95% CI: 0.64 to 9.65; P = 0.11; NNT = 4.5).Clinical improvement in group A correlated with a decrease of IL-8 and MCP-1. Rates of adverse events did not differ significantly between both groups.CONCLUSION: In group A (oral NAC combined with mesalamine) contrarily to group B (mesalamine alone),the clinical improvement correlates with a decrease of chemokines such as MCP-1 and IL-8. NAC addition not produced any side effects.

  7. Preparation and evaluation of magnetic microspheres of mesalamine (5-aminosalicylic acid) for colon drug delivery

    Institute of Scientific and Technical Information of China (English)

    Satinder Kakar; Deepa Batra; Ramandeep Singh

    2013-01-01

    Objective:To study magnetic microspheres of mesalamine(5-aminosalicylic acid) for colon drug delivery.Methods:Magnetic microspheres were prepared by solvent evaporation technique for use in the application of magnetic carrier technology.An attempt was made to target mesalamine (5-aminosalicylic acid) to its site of action i.e. to colon.EudragitS-100, ethylcellulose and chitosan were used in three different drug: polymer ratios i.e.1:1,1:2 and1:3.The microspheres were characterized in terms of particle size, percentage yield, drug content, encapsulation efficiency,in vitro release pattern andex vivo study.The microspheres were uniform in size and shape.Thein vitrorelease profile was studied in pH7.4 phosphate buffer medium usingUSP dissolution apparatus.Results:Chitosan microspheres were found to be better retained in terms of percentage release of the drug.Thus chitosan microspheres could be better retained at their target site.Conclustion:Flow characteristics are also better in case of chitosan magnetic microspheres. Thus reticuloendothelial clearance can be minimized and site specificity can be increased.

  8. Novel mesalamine-loaded beads in tablets for delayed release of drug to the colon.

    Science.gov (United States)

    Nguyen, Chien; Christensen, J Mark; Ayres, James W

    2012-01-01

    Novel 'beads-in-a-tablet' formulations (total weight ∼740-780 mg) have been prepared that meet USP 31 requirements for Delayed Release of mesalamine. Several methods are presented that overcome breakage of beads during tablet compaction were explored. Bead formulations comprise a combination of extrusion and spheronization to produce a relatively high drug load (80%), followed by coating (25%) with a colonic-targeted drug release polymer (polymethacrylates, Eudragit(®) S100), overcoated (3%) with hydroxypropyl methylcellulose (Opadry(®)) to improve bead binding and compactability, and using 20% coat of lactose/sodium starch glycolate (Explotab(®)) as binder/disintegrant/cushioning agent, thus allowing a sufficiently thick coating to be uniform and without being broken during tablet compaction. Then, the aforementioned beads were compressed into tablets at 1500 pounds of pressure containing 400 mg of mesalamine, and finally coating the compressed tablets with Surelease(®) (ethylcellulose):Opadry(®) = 1:0.5 ranging from 1.5-2.5% weight gain; the resulting tablets met USP 31 dissolution requirements for delayed release tablets.

  9. Efficacy and Safety of Mesalamine Suppositories for Treatment of Ulcerative Proctitis in Children and Adolescents

    Science.gov (United States)

    Heyman, Melvin B.; Kierkus, Jaroslaw; Spénard, Jean; Shbaklo, Hadia; Giguere, Monique

    2011-01-01

    Background Treatment of ulcerative proctitis has not been well studied in pediatric populations. We conducted an open-label trial to evaluate the clinical efficacy of a mesalamine suppository (500 mg) to treat pediatric patients with mild to moderate ulcerative proctitis. Methods Pediatric patients (5–17 years of age) with ulcerative proctitis were enrolled for baseline evaluations, including a flexible sigmoidoscopic (or colonoscopic) assessment with biopsies performed at study entry. Eligible patients were started on mesalamine suppositories (500 mg) at bedtime. Two follow-up visits were scheduled after 3 and 6 weeks of treatment. The dose could be increased to 500 mg twice daily at the week 3 follow-up visit if deemed appropriate by the investigator based on the Disease Activity Index (DAI) assessment. The primary outcome measure was a DAI derived from a composite score of stool frequency, urgency of defecation, rectal bleeding, and general well-being. Results Forty-nine patients were included in the intent-to-treat analysis. The mean DAI value decreased from 5.5 at baseline to 1.6 and 1.5 at weeks 3 and 6, respectively (P suppository is safe and efficacious in children with ulcerative proctitis. PMID:20848454

  10. The study of marketed and experimental formulation approaches enabling site-specific delivery of mesalamine in patients with inflammatory bowel disease.

    Science.gov (United States)

    Kadiyala, Irina; Jacobs, Dylan

    2014-04-01

    This patent review focuses exclusively on the oral delivery of mesalamine (5-ASA) and excludes oral mesalamine pro-drug and rectal delivery formulations. The formulation strategies of marketed formulations (Apriso(®), Asacol(®), Lialda(®) and Pentasa(®)) and non-marketed formulations are reviewed and explained by decoding formulation specifics that enable the site specific delivery for the treatment of inflammatory bowel disease.

  11. Improved glycemic control with no weight increase in patients with type 2 diabetes after once-daily treatment with the long-acting glucagon-like peptide 1 analog liraglutide (NN2211): a 12-week, double-blind, randomized, controlled trial

    DEFF Research Database (Denmark)

    Madsbad, Sten; Schmitz, Ole; Ranstam, Jonas

    2004-01-01

    -group, placebo-controlled trial with an open-label comparator arm was conducted among 193 outpatients with type 2 diabetes. The mean age was 56.6 years and the mean HbA(1c) was 7.6% across the treatment groups. Patients were randomly assigned to one of five fixed-dosage groups of liraglutide (0.045, 0.225, 0....... Patients treated with glimepiride had decreased HbA(1c) and fasting glucose, but slightly increased body weight. No safety issues were raised for liraglutide; observed adverse events were mild and transient. CONCLUSIONS: A once-daily dose of liraglutide provides efficacious glycemic control...

  12. Molecular modeling and multispectroscopic studies of the interaction of mesalamine with bovine serum albumin

    Science.gov (United States)

    Shahabadi, Nahid; Fili, Soraya Moradi

    2014-01-01

    The interaction of mesalamine (5-aminosalicylic acid (5-ASA)) with bovine serum albumin (BSA) was investigated by fluorescence quenching, absorption spectroscopy, circular dichroism (CD) techniques, and molecular docking. Thermodynamic parameters (ΔH < 0 and ΔS 0) indicated that the hydrogen bond and electrostatic forces played the major role in the binding of 5-ASA to BSA. The results of CD and UV-vis spectroscopy showed that the binding of this drug to BSA induces some conformational changes in BSA. Displacement experiments predicted that the binding of 5-ASA to BSA is located within domain III, Sudlows site 2, that these observations were substantiated by molecular docking studies. In addition, the docking result shows that the 5-ASA in its anionic form mainly interacts with Gln-416 residue through one hydrogen bond between H atom of 5-ASA anion and the adjacent O atom of the hydroxyl group of Gln-416.

  13. A Randomized Single Blind Parallel Group Study Comparing Monoherbal Formulation Containing Holarrhena antidysenterica Extract with Mesalamine in Chronic Ulcerative Colitis Patients

    Directory of Open Access Journals (Sweden)

    Sarika Johari

    2016-01-01

    Full Text Available Background: Incidences of side effects and relapses are very common in chronic ulcerative colitis patients after termination of the treatment. Aims and Objectives: This study aims to compare the treatment with monoherbal formulation of Holarrhena antidysenterica with Mesalamine in chronic ulcerative colitis patients with special emphasis to side effects and relapse. Settings and Design: Patients were enrolled from an Ayurveda Hospital and a private Hospital, Gujarat. The study was randomized, parallel group and single blind design. Materials and Methods: The protocol was approved by Institutional Human Research Ethics Committee of Anand Pharmacy College on 23rd Jan 2013. Three groups (n = 10 were treated with drug Mesalamine (Group I, monoherbal tablet (Group II and combination of both (Group III respectively. Baseline characteristics, factors affecting quality of life, chronicity of disease, signs and symptoms, body weight and laboratory investigations were recorded. Side effects and complications developed, if any were recorded during and after the study. Statistical Analysis Used: Results were expressed as mean ± SEM. Data was statistically evaluated using t-test, Wilcoxon test, Mann Whitney U test, Kruskal Wallis test and ANOVA, wherever applicable, using GraphPad Prism 6. Results: All the groups responded positively to the treatments. All the patients were positive for occult blood in stool which reversed significantly after treatment along with rise in hemoglobin. Patients treated with herbal tablets alone showed maximal reduction in abdominal pain, diarrhea, and bowel frequency and stool consistency scores than Mesalamine treated patients. Treatment with herbal tablet alone and in combination with Mesalamine significantly reduced the stool infection. Patients treated with herbal drug alone and in combination did not report any side effects, relapse or complications while 50% patients treated with Mesalamine exhibited the relapse with

  14. Fabrication of an electrochemical sensor based on computationally designed molecularly imprinted polymer for the determination of mesalamine in real samples.

    Science.gov (United States)

    Torkashvand, M; Gholivand, M B; Taherkhani, F

    2015-10-01

    A novel electrochemical sensor based on mesalamine molecularly imprinted polymer (MIP) film on a glassy carbon electrode was fabricated. Density functional theory (DFT) in gas and solution phases was developed to study the intermolecular interactions in the pre-polymerization mixture and to find the suitable functional monomers in MIP preparation. On the basis of computational results, o-phenylenediamine (OP), gallic acid (GA) and p-aminobenzoic acid (ABA) were selected as functional monomers. The MIP film was cast on glassy carbon electrode by electropolymerization of solution containing ternary monomers and then followed by Ag dendrites (AgDs) with nanobranch deposition. The surface feature of the modified electrode (AgDs/MIP/GCE) was characterized by scanning electron microscopy (SEM) and electrochemical impedance spectroscopy (EIS). Under the optimal experimental conditions, the peak current was proportional to the concentration of mesalamine ranging from 0.05 to 100 μM, with the detection limit of 0.015 μM. The proposed sensor was applied successfully for mesalamine determination in real samples.

  15. Chronopharmacokinetics of once daily dosed aminoglycosides in hospitalized infectious patients

    NARCIS (Netherlands)

    van Maarseveen, Erik; Man, Wai Hong; Proost, Johannes; Neef, Cees; Touw, Daniël

    2015-01-01

    BACKGROUND: hospitalized patients with serious infections treated with aminoglycosides are at risk of developing nephrotoxicity. Previous clinical studies have shown that the pharmacokinetics of aminoglycosides in humans follow a circadian rhythm. Therefore, the time of administration could have imp

  16. Chronopharmacokinetics of once daily dosed aminoglycosides in hospitalized infectious patients

    NARCIS (Netherlands)

    van Maarseveen, Erik; Man, Wai Hong; Proost, Johannes; Neef, Cees; Touw, Daniel

    2015-01-01

    Background hospitalized patients with serious infections treated with aminoglycosides are at risk of developing nephrotoxicity. Previous clinical studies have shown that the pharmacokinetics of aminoglycosides in humans follow a circadian rhythm. Therefore, the time of administration could have impo

  17. ONCE DAILY FELODIPINE IN PATIENTS WITH PRIMARY RAYNAUDS-PHENOMENON

    NARCIS (Netherlands)

    KALLENBERG, CGM; WOUDA, AA; WESSELING, H

    1991-01-01

    The symptomatic effects of felodipine (Plendil(R)) have been assessed in 10 patients with primary Raynaud's phenomenon in a single blind study. After 2 weeks on placebo, the patients were treated for 6 weeks with felodipine, the dose being titrated stepwise every 2 weeks, starting with 5 mg, and inc

  18. The immunologic effects of mesalamine in treated HIV-infected individuals with incomplete CD4+ T cell recovery: a randomized crossover trial.

    Directory of Open Access Journals (Sweden)

    Ma Somsouk

    Full Text Available The anti-inflammatory agent, mesalamine (5-aminosalicylic acid has been shown to decrease mucosal inflammation in ulcerative colitis. The effect of mesalamine in HIV-infected individuals, who exhibit abnormal mucosal immune activation and microbial translocation (MT, has not been established in a placebo-controlled trial. We randomized 33 HIV-infected subjects with CD4 counts <350 cells/mm3 and plasma HIV RNA levels <40 copies/ml on antiretroviral therapy (ART to add mesalamine vs. placebo to their existing regimen for 12 weeks followed by a 12 week crossover to the other arm. Compared to placebo-treated subjects, mesalamine-treated subjects did not experience any significant change in the percent CD38+HLA-DR+ peripheral blood CD4+ and CD8+ T cells at week 12 (P = 0.38 and P = 0.63, respectively, or in the CD4+ T cell count at week 12 (P = 0.83. The percent CD38+HLA-DR+ CD4+ and CD8+ T cells also did not change significantly in rectal tissue (P = 0.86, P = 0.84, respectively. During the period of mesalamine administration, plasma sCD14, IL-6, D-dimer, and kynurenine to tryptophan ratio were not changed significantly at week 12 and were similarly unchanged at week 24. This study suggests that, at least under the conditions studied, the persistent immune activation associated with HIV infection is not impacted by the anti-inflammatory effects of mesalamine.ClinicalTrials.gov NCT01090102.

  19. SPECTROPHOTOMETRIC METHOD FOR SIMULTANEOUS ESTIMATION OF MESALAMINE AND PREDNISOLONE IN COMBINED ORAL DOSAGE FORM

    Directory of Open Access Journals (Sweden)

    Dr. Sanjay Jain et al

    2012-10-01

    Full Text Available The objective of this study was to develop simple, precise, accurate, reproducible and economical vireodt's method for simultaneous estimation of mesalamine (MSM and prednisolone (PRD in combined oral dosage form. The method involved measurement of absorbance at two wavelengths, 332nm and 246nm, λmax of MSM and PRD, respectively in phosphate buffer (pH 7.4 with dimethyl formamide (DMF as cosolvent. The linearity was obtained in the concentration range of 5-50 µg/ml and 2-20 µg/ml for MSM and PRD, respectively. The average percent recovery of MSM and PRD was found to be 99.19+0.78% and 99.71+0.82%, respectively. The accuracy and precision were determined and recovery studies confirmed the accuracy of the developed method that was carried out following the International Conference on Harmonization (ICH guidelines. The recovery study was carried out by standard addition method. The proposed method was found to be rapid, specific, precise, accurate, and reproducible and can be successfully applied for the routine analysis of MSM and PRD in pharmaceutical dosage form.

  20. Successful treatment for ulcerative proctitis with rectal tacrolimus in an 8-year-old girl with intolerance to mesalamine.

    Science.gov (United States)

    Navas-López, Víctor Manuel; Blasco-Alonso, Javier; Girón Fernández-Crehuet, Francisco; Serrano Nieto, Maria Juliana; Gallego-Gutiérrez, Silvia; Luque Pérez, Silvia; Sierra Salinas, Carlos

    2014-08-01

    Ulcerative colitis (UC) is defined as a chronic inflammatory condition causing continuous mucosal inflammation of the colon without granulomas on biopsy. It affects the rectum, and, to a variable extent, the colon in continuity and is characterized by a relapsing and remitting course. Oral 5-aminosalicylic acid (5-ASA) regimens are recommended as first-line induction therapy for mild to moderately active pediatric UC and for maintenance of remission regardless of other initial treatments. In large clinical trials in adults, mesalamine intolerance was found in 2-5 % of the patients. We present a case of an 8-year-old female patient with intolerance to mesalamine and proctitis resistant to conventional therapy who responded to rectal tacrolimus treatment. The patient started with a dose of 2 mg/day at night with an excellent response. She reported feeling better than any of the previously prescribed treatments and without feeling the discomfort of previously administered enemas. After four weeks of treatment, the dose was reduced to 2 mg/week with no relapses. Tacrolimus suppositories were very well tolerated, and no adverse effects have been reported. Although only very little data has been published, rectal tacrolimus seems to be safe and of efficacy in ulcerative proctitis resistant to standard therapy.

  1. Comparative protective effect of hawthorn berry hydroalcoholic extract, atorvastatin, and mesalamine on experimentally induced colitis in rats.

    Science.gov (United States)

    Malekinejad, Hassan; Shafie-Irannejad, Vahid; Hobbenaghi, Rahim; Tabatabaie, Seyed Hamed; Moshtaghion, Seyed-Mehdi

    2013-07-01

    The protective effect of hydroalcoholic extract of hawthorn berries (HBE) on acetic acid (AA)-induced colitis in rats was investigated. Forty-two Wistar rats were divided into seven groups, including control and test groups (n=6). The control animals received saline, and the test animals were treated with saline (sham group), mesalamine (50 mg/kg; M group), atorvastatin (20 mg/kg; A group), HBE (100 mg/kg; H group), mesalamine and HBE (HM group), or atorvastatin plus HBE (HA group), 3 days before and a week after colitis induction. Colitis was induced by administration of 1 mL AA (4%) via a polyethylene catheter intrarectally. High-performance liquid chromatography analyses showed that HBE contained 0.13% and 0.5% oleanolic acid and ursolic acid, respectively. Elevated myeloperoxidase activity and lipid peroxidation were attenuated in the HA group. The H and HM groups showed marked reductions in colitis-induced decreases in total thiol molecules and body weight. The histopathological studies revealed that HBE decreased colitis-induced edema and infiltration of neutrophils. Our data suggest the anti-inflammatory and antioxidant effects of HBE and atorvastatin protect against AA-induced colitis. The anti-inflammatory effect of HBE may be attributable to its ability to decrease myeloperoxidase activity as a biomarker of neutrophil infiltration.

  2. Carboxymethyl starch and lecithin complex as matrix for targeted drug delivery: I. Monolithic mesalamine forms for colon delivery.

    Science.gov (United States)

    Mihaela Friciu, Maria; Canh Le, Tien; Ispas-Szabo, Pompilia; Mateescu, Mircea Alexandru

    2013-11-01

    For drugs expected to act locally in the colon, and for successful treatment, a delivery device is necessary, in order to limit the systemic absorption which decreases effectiveness and causes important side effects. Various delayed release systems are currently commercialized; most of them based on pH-dependent release which is sensitive to gastrointestinal pH variation. This study proposes a novel excipient for colon delivery. This new preparation consists in the complexation between carboxymethyl starch (CMS) and Lecithin (L). As opposed to existing excipients, the new complex is pH-independent, inexpensive, and easy to manufacture and allows a high drug loading. FTIR, X-ray, and SEM structural analysis all support the hypothesis of the formation of a complex. By minor variation of the excipient content within the tablet, it is possible to modulate the release time and delivery at specific sites of the gastrointestinal tract. This study opens the door to a new pH-independent delivery system for mesalamine targeted administration. Our novel formulation fits well with the posology of mesalamine, used in the treatment of Inflammatory Bowel Disease (IBD), which requires repeated administrations (1g orally four times a day) to maintain a good quality of life. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. Comparison of the analgesic effect of ibuprofen with mesalamine after discectomy surgery in patients with lumbar disc herniation: A double-blind randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Toroudi Hamidreza

    2009-01-01

    Full Text Available Background: Pain management is an important component in the postoperative period following discectomy. Aims: We hypothesized that mesalamine considering its better safety profile, is likely to be a better choice, if it would be as effective as ibuprofen in controlling post-discectomy pain. Settings and Design: A double-blind randomized controlled trial was performed on patients who underwent lumbar discectomy surgery. Materials and Methods: Of the 58 patients who had lumbar discectomy, 27 patients were randomized to oral ibuprofen 500 mg and 31 patients to mesalamine 400 mg, three times a day for nine days following surgery. There was no placebo group. Severity of pain was assessed by using 10- cm visual analogue scale (VAS, once before operation and for nine days after. Statistical Analysis: Mean ± SD pain scores were compared between groups and the statistical difference was estimated by Student′s test using SPSS (Version 13. We also calculated the power of each t-test. Repeated measure ANOVA was performed for measuring the effect of time. Results: The age range of the patients was 35 to 60 years (mean: 42.2 years. Mean ± SD preoperative pain scores for ibuprofen or mesalamine-treated groups were 7.852 ± 2.441 and 7.806 ± 2.892, respectively. At the end of day 9, mean ± SD of pain score was 2.704 ± 2.284 and 2.717 ± 2.273 for ibuprofen and mesalamine-treated groups respectively. Both drugs significantly reduced postoperative pain and there was no statistically significant difference between the two groups.Conclusions: Since both drugs showed almost equal analgesic effect, considering its safety profile mesalamine, seems to be the preferred choice to alleviate post-discectomy surgery pain.

  4. A randomized, controlled trial of initial anti-retroviral therapy with abacavir/lamivudine/zidovudine twice-daily compared to atazanavir once-daily with lamivudine/zidovudine twice-daily in HIV-infected patients over 48 weeks (ESS100327, the ACTION Study

    Directory of Open Access Journals (Sweden)

    McClernon Daniel

    2009-04-01

    Full Text Available Abstract Background Traditional first line regimens containing a non-nucleoside reverse transcriptase inhibitor or protease inhibitor may not be suitable for a subset of antiretroviral-naïve patients such as those with certain co-morbidities, women of child-bearing potential, and intolerability to components of standard first line therapy. This study was conducted to determine if alternate treatment options may meet the needs of both general and special patient populations. The ACTION study was a randomized, open-label, multicenter, 48-week trial that compared the safety and efficacy of a triple nucleoside regimen versus a protease inhibitor plus a dual nucleoside regimen in HIV-1 treatment-naïve subjects. Results 279 HIV-infected subjects with HIV-1 RNA (VL >5000 but 3 were randomized (1:1 to receive abacavir sulfate/lamivudine/zidovudine (ABC/3TC/ZDV twice-daily or atazanavir (ATV once-daily plus lamivudine/zidovudine (3TC/ZDV twice-daily. Protocol-defined virologic failure was based on multiple failure criteria. Non-inferiority of ABC/3TC/ZDV to ATV+3TC/ZDV was established with 62% vs. 59% of subjects achieving a VL Conclusion ABC/3TC/ZDV demonstrated comparable virologic efficacy to ATV+3TC/ZDV in this population over 48 weeks. In those with a baseline VL ≥ 100,000 c/mL, subjects in the ATV+3TC/ZDV showed better virologic efficacy. Both regimens offer benefits in select therapy-naïve subjects. Trial Registration [Clinical Trials Identifier, NCT00082394].

  5. Study on the interaction of the drug mesalamine with calf thymus DNA using molecular docking and spectroscopic techniques.

    Science.gov (United States)

    Shahabadi, Nahid; Fili, Soraya Moradi; Kheirdoosh, Fahimeh

    2013-11-05

    The interaction of CT-DNA with the drug mesalamine (5-ASA) at physiological pH has been investigated by absorption, emission, circular dichroism (CD), cyclic voltammetry (CV), viscosity studies and molecular modeling. Thermodynamic parameters (ΔH>0 and ΔS<0) indicated that hydrogen bond and van der Waals play main roles in the binding of 5-ASA to CT-DNA. Ethidium bromide (EB) displacement studies revealed that 5-ASA did not have any effect on ethidium bromide (EB) bound DNA which is indicative of groove binding. The results obtained from experimental and molecular modeling showed that 5-ASA is a minor groove binder of DNA and preferentially binds to GC rich regions.

  6. Preparation and characterization of glycidyl methacrylate organo bridges grafted mesoporous silica SBA-15 as ibuprofen and mesalamine carrier for controlled release.

    Science.gov (United States)

    Rehman, Fozia; Rahim, Abdur; Airoldi, Claudio; Volpe, Pedro L O

    2016-02-01

    Mesoporous silica SBA-15 was synthesized and functionalized with bridged polysilsesquioxane monomers obtained by the reaction of 3-aminopropyltriethoxy silane with glycidyl methacrylate in 2:1 ratio. The synthesized mesoporous silica materials were characterized by elemental analysis, infrared spectroscopy, nuclear magnetic resonance spectroscopy, nitrogen adsorption, X-ray diffraction, thermogravimetry and scanning electron microscopy. The nuclear magnetic resonance in the solid state is in agreement with the sequence of carbon distributed in the attached organic chains, as expected for organically functionalized mesoporous silica. After functionalization with organic bridges the BET surface area was reduced from 1311.80 to 494.2m(2)g(-1) and pore volume was reduced from 1.98 to 0.89cm(3)g(-1), when compared to original precursor silica. Modification of the silica surface with organic bridges resulted in high loading capacity and controlled release of ibuprofen and mesalamine in biological fluids. The Korsmeyer-Peppas model better fits the release data indicating Fickian diffusion and zero order kinetics for synthesized mesoporous silica. The drug release rate from the modified silica was slow in simulated gastric fluid, (pH1.2) where less than 10% of mesalamine and ibuprofen were released in initial 8h, while comparatively high release rates were observed in simulated intestinal (pH6.8) and simulated body fluids (pH7.2). The preferential release of mesalamine at intestinal pH suggests that the modified silica could be a simple, efficient, inexpensive and convenient carrier for colon targeted drugs, such a mesalamine and also as a controlled drug release system.

  7. A novel stimuli-synchronized alloy-treated matrix for space-defined gastrointestinal delivery of mesalamine in the Large White pig model.

    Science.gov (United States)

    Bawa, Priya; Choonara, Yahya E; du Toit, Lisa C; Kumar, Pradeep; Ndesendo, Valence M K; Meyer, Leith C R; Pillay, Viness

    2013-03-28

    The study focussed on designing a Stimuli-Synchronized Matrix (SSM) for space-defined colonic delivery of the anti-inflammatory drug mesalamine. The configured matrix provided time-independent delivery and stimuli targeting. Formulations were optimized according to a Box-Behnken experimental design that constituted mesalamine-loaded BaSO4-crosslinked chitosan dispersed within a pectin, carboxymethylcellulose and xanthan gum complex. The complex was compressed into matrices and subsequently alloy-treated with pectin and ethylcellulose. In vitro drug release was determined in the presence and absence of colonic enzymes and the mean dissolution time was used for formulation optimization. To mechanistically elucidate the synchronous catalytic action of the enzymes pectinase and glucosidase on the matrix, computer-aided 3D modelling of active fractions of the enzyme-substrate complexes was generated to predict the orientation of residues affecting the substrate domain. Drug release profiles revealed distinct colonic enzyme responsiveness with fractions of 0.402 and 0.152 of mesalamine released in the presence and absence of enzymes, respectively after 24h. The commercial comparator product showed irreproducible release profiles over the same period (SD=0.550) compared to the SSM formulation (SD=0.037). FTIR spectra of alloy-treated matrices showed no peaks from 1589 to 1512cm(-1) after colonic enzyme exposure. With increasing enzyme exposure there were also no peaks between 1646 and 1132cm(-1). This indicated polymeric enzyme cleavage for controlled and space-defined release of mesalamine. Plasma concentration profiles in the Large White pig model produced a Cmax of 3.77±1.375μg/mL compared to 10.604±2.846μg/mL for the comparator formulation. The SSM formulation proved superior over the comparator product by providing superiorly controlled enzyme-responsive colonic drug delivery.

  8. Effect of Mesalamine and Prednisolone on TNBS Experimental Colitis, following Various Doses of Orally Administered Iron

    Directory of Open Access Journals (Sweden)

    John K. Triantafillidis

    2014-01-01

    Full Text Available Background. Experimental data suggest that oral iron (I. supplementation can worsen colitis in animals. Aim. To investigate the influence of various concentrations of orally administered I. in normal gut mucosa and mucosa of animals with TNBS colitis, as well as the influence of Mesalamine (M. and Prednisolone (P. on the severity of TNBS colitis following orally administered I. Methods and Materials. 156 Wistar rats were allocated into 10 groups. Colitis was induced by TNBS. On the 8th day, all animals were euthanatized. Activity of colitis and extent of tissue damage were assessed histologically. The levels of tissue tumor necrosis factor-α (t-TNF-α and tissue malondialdehyde (t-MDA were estimated in all animal groups. Results. Moderate and high I. supplementation induced inflammation in the healthy colon and increased the activity of the experimentally induced TNBS colitis. Administration of M. on TNBS colitis following moderate iron supplementation (0.3 g/Kg diet resulted in a significant improvement in the overall histological score as well as in two individual histological parameters. M. administration, however, did not significantly reduce the t-TNF-α levels (17.67±4.92 versus 14.58±5.71, P=0.102, although it significantly reduced the t-MDA levels (5.79±1.55 versus 3.67±1.39, P=0.000. Administration of M. on TNBS colitis following high iron supplementation (3.0 g/Kg diet did not improve the overall histological score and the individual histological parameters, neither reduced the levels of t-TNF-α (16.57 ± 5.61 versus 14.65±3.88, P=0.296. However, M. significantly reduced the t-MDA levels (5.99±1.37 versus 4.04±1.41, P=0.000. Administration of P. on TNBS colitis after moderate iron supplementation resulted in a significant improvement in the overall histological score as well as in three individual histological parameters. P. also resulted in a significant reduction in the t-TNF-α levels (17.67±4.92 versus 12.64±3

  9. Evaluation of Pharmaceutical Quality of Mesalamine Delayed Release Tablets Using a New High Sensitivity Reversed-Phase UPLC Method for its Genotoxic/Aniline Impurity

    Directory of Open Access Journals (Sweden)

    Rakshit Kanubhai Trivedi

    2011-01-01

    Full Text Available A reversed phase ultra performance liquid chromatography (UPLC method was developed and validated for the quantification of aniline in mesalamine delayed-release tablets. The optimization of the experimental condition was carried out considering some important requirements like, detection limit, short run time and reproducibility. In the present study, isocratic reversed-phase UPLC method was developed for determination and separation of aniline from the drug product. The drug and impurity are well separated by using a reversed phase (Reprosil Gold C18-XBD column and mobile phase comprising of buffer pH 6.0 and acetonitrile in the ratio of 90:10 v/v. Other UPLC parameters which were optimised are flow rate, 0.5 mL/min; detection wavelength, 200 nm; column oven temperature, 50 °C and injection volume 7 µL. Stability indicating capability was also established by forced degradation experiments. The method was validated as per ICH guideline. LOQ (limit of quantification concentration (18 ng/mL was found precise with RSD of less than 2%. In essence, the present study provides an improved low detection limit and lower run time for evaluation of pharmaceutical quality of mesalamine delayed-release formulation. Moreover, the developed method was also successfully applied for quantification of aniline in mesalamine delayed-release formulation. The same method can also be used for determination of aniline from drug substances.

  10. 双时相门冬胰岛素30每日1次对2型糖尿病患者的疗效和安全性%Efficacy and safety of once-daily biphasic insulin aspart 30 in insulin-na(i)ve patients with type 2 diabetes

    Institute of Scientific and Technical Information of China (English)

    Easy Start Study(ESS)协作组

    2011-01-01

    .The efficacy and safety of BIAsp 30 once-daily for 12-week were assessed in these patients. Baseline factors potentially impact treatment efficacy were investigated too.Results Baseline demographic characteristics of the 621 patients were summarized as follows: mean age (56±11) years,mean duration of diabetes (4.4 ±4.2 )years,mean body mass index(BMI) (25.5 ±2.9)kg/m2; baseline glycosylated hemoglobin(HbA1c) 8.5% ± 1.2%.The initial and final doses of BIAsp 30 was (0.16 ± 0.05 )U/kg and (0.20 ± 0.07 )U/kg,respectively.After 12-week of treatment,HbA1c decreased by 1.8% ± 1.1% on average,and 30.8% of patients achieved a HbA1c < 6.5% and 65.5% of patients achieved a HbA1c < 7.0%. The fasting and postprandial plasma glucose improved significantly and the mean value of 8-point plasma glucose decreased by ( 3.8 ± 2.3 ) mmol/L.The percentage of patients achieving HbA 1 c target decreased along with the increase of baseline HbA1 c level andthe duration of diabetes.No difference of glycaemic control was observed between the groups of pre-breakfast and pre-dinner injection.The rate of minor hypoglycaemia was 1.83 events per patient per year.Only one case of major hypoglycaemia (nocturnal) was reported.There was no significant body-weight gain before and after treatment.No adverse event reported as related to study drugs was observed.Conclusion For the insulin naive patients,BIAsp 30 once-daily,as insulin initiation,could improve glycaemic control without compromising safety and convenience,especially for the patients with lower HbA1c level and shorter duration of diabetes.

  11. Influence of some formulation variables on the optimization of pH-dependent, colon-targeted, sustained-release mesalamine microspheres.

    Science.gov (United States)

    El-Bary, Ahmed Abd; Aboelwafa, Ahmed A; Al Sharabi, Ibrahim M

    2012-03-01

    The aim of this work was to understand the influence of different formulation variables on the optimization of pH-dependent, colon-targeted, sustained-release mesalamine microspheres prepared by O/O emulsion solvent evaporation method, employing pH-dependent Eudragit S and hydrophobic pH-independent ethylcellulose polymers. Formulation variables studied included concentration of Eudragit S in the internal phase and the ratios between; internal to external phase, drug to Eudragit S and Eudragit S to ethylcellulose to mesalamine. Prepared microspheres were evaluated by carrying out in vitro release studies and determination of particle size, production yield, and encapsulation efficiency. In addition, morphology of microspheres was examined using optical and scanning electron microscopy. Emulsion solvent evaporation method was found to be sensitive to the studied formulation variables. Particle size and encapsulation efficiency increased by increasing Eudragit S concentration in the internal phase, ratio of internal to external phase, and ratio of Eudragit S to the drug. Employing Eudragit S alone in preparation of the microspheres is only successful in forming acid-resistant microspheres with pulsatile release pattern at high pH. Eudragit S and ethylcellulose blend microspheres were able to control release under acidic condition and to extend drug release at high pH. The stability studies carried out at 40°C/75% RH for 6 months proved the stability of the optimized formulation. From the results of this investigation, microencapsulation of mesalamine in microspheres using blend of Eudragit S and ethylcellulose could constitute a promising approach for site-specific and controlled delivery of drug in colon.

  12. Formulation development, optimization and study on drug release kinetics of Eudragit® L100-HPMC E15 LV mixed film-coated colon-targeted Mesalamine tablets

    Directory of Open Access Journals (Sweden)

    A Maria John Newton

    2012-01-01

    Full Text Available The study was designed to evaluate the in vitro dissolution characteristics of pH-sensitive polymer - HPMC E 15 LV-coated tablets - in various simulated fluids (pH range 1.2, 6, 7.2. The Mesalamine tablets were fabricated by mixing the drug with microcrystalline cellulose and other ingredients. The fabricated Mesalamine tablets were coated with Eudragit L100 polymer and HPMC E 15 LV. The fluctuation in colonic pH conditions during inflammatory bowel disease and the nature of less fluid content in the colon may limit the expected drug release in the colon. Addition of HPMC E 15 LV may control this problem by hydrophilic nature and excellent film-forming characteristics like ductility and elasticity. The different batches of Mesalamine tablets (FM1-FM5 were coated with increasing concentration of Eudragit L100 and HPMC E 15 LV. The coating was given up to 8% TWG(Total weight gain of the uncoated tablet. Drug release studies were conducted in different pH conditions in the presence of rat ceaecal contents. The different buffer conditions were chosen to mimic the pH changes in the terminal part of the ileum as well as in the colon. The drug release profile was analyzed for colon-targeting performance in vitro. The release profile of the tablets indicates that the drug release was retarded in the tablet by film coating. The addition of HPMC E 15 LV ensures the channels for allowing colonic fluids to penetrate into the core and subsequent drug release at the target site. The kinetics of the drug release also evaluated the release pattern that was best fitted with Higuchian release. The results of the mechanism of release revealed that drug release was found to be a complex one with diffusion, erosion and swelling.

  13. A Multicenter, Randomized Study to Evaluate the Efficacy and Safety of Mesalamine Suppositories 1 g at Bedtime and 500 mg Twice Daily in Patients with Active Mild-to-Moderate Ulcerative Proctitis

    Science.gov (United States)

    2010-01-01

    Abstract Background Ulcerative proctitis (UP) is a prevalent condition associated with increased morbidity and mortality. Topical mesalamine (5-aminosalicylic acid [5-ASA]) inhibits inflammatory processes in UP. Methods We evaluated effects of mesalamine 1-g suppository administered QHS compared with 500-mg suppository administered BID on UP activity (e.g., disease extension/mucosal appearance), remission, onset of response, safety and compliance in 97 patients with UP. A 6-week, randomized, multicenter, parallel-group, noninferiority study was conducted (and published) with Disease Activity Index (DAI) at week 6 as the primary efficacy variable and individual components of DAI at week 6 (i.e., stool frequency, rectal bleeding, mucosal appearance, global assessment) as secondary variables. Unreported outcomes were remission (DAI 70%) after 6 weeks in both groups. Mesalamine was well tolerated. Compliance was >96%. Conclusions Mesalamine 500-mg BID and 1-g QHS suppositories are safe and effective for patients with UP. Most patients reported significant improvement within 3 weeks and UP remission and reduced disease extension after 6 weeks of treatment. Validity of QHS administration was confirmed. PMID:20676771

  14. Modulation of N-glycosylation by mesalamine facilitates membranous E-cadherin expression in colon epithelial cells.

    Science.gov (United States)

    Khare, Vineeta; Lang, Michaela; Dammann, Kyle; Campregher, Christoph; Lyakhovich, Alex; Gasche, Christoph

    2014-01-15

    Genome wide association studies have implicated intestinal barrier function genes in the pathogenesis of ulcerative colitis. One of such loci CDH1, encoding E-cadherin, a transmembrane glycoprotein with known tumor suppressor functions, is also linked to the susceptibility to colorectal cancer. Loss of membranous E-cadherin expression is common in both colitis and cancer. We have recently demonstrated that mesalamine (5-ASA); the anti-inflammatory drug used to treat ulcerative colitis, induces membranous expression of E-cadherin and increases intercellular adhesion. Using colorectal cancer epithelial cells with aberrant E-cadherin expression, we investigated the mechanism underlying such an effect of 5-ASA. Post-translational modification of E-cadherin glycosylation was analyzed by biotin/streptavidin detection of sialylated glycoproteins. GnT-III (N-acetylglucosaminyltransferase III) expression was assessed by qRT-PCR, Western blot and immunofluorescence. GnT-III activity was analyzed by reactivity with E-4/L-4-PHA. Expression, localization and interaction of E-cadherin and β-catenin were analyzed by Western blot, immunocytochemistry and RNA interference. 5-ASA activity modulated E-cadherin glycosylation and increased both mRNA and protein levels of GnT-III and its activity as detected by increased E4-lectin reactivity. Intestinal APC(Min) polyps in mice showed low expression of GnT-III and 5-ASA was effective in increasing its expression. The data demonstrated that remodeling of glycans by GnT-III mediated bisect glycosylation, contributes to the membranous retention of E-cadherin by 5-ASA; facilitating intercellular adhesion. Induction of membranous expression of E-cadherin by 5-ASA is a novel mechanism for mucosal healing in colitis that might impede tumor progression by modulation of GnT-III expression.

  15. Box-Behnken experimental design in the development of pectin-compritol ATO 888 compression coated colon targeted drug delivery of mesalamine.

    Science.gov (United States)

    Patel, Nirav V; Patel, Jayvadan K; Shah, Shreeraj H

    2010-03-01

    The aim of this study was to investigate the combined influence of 3 independent variables in the compression coated tablet of mesalamine for ulcerative colitis. A 3-factor, 3-level Box-Behnken design was used to derive a second order polynomial equation and construct contour plots to predict responses. The independent variables selected were: percentage of polymers (pectin and compritol ATO 888) in compression coating (X(1)), coating mass (X(2)) and coating force (X(3)). Fifteen batches were prepared and evaluated for percent of drug released in 5 h (Y(5)), time required for 50 % mesalamine to dissolve (t(50)) with rat cecal (RC) content and without rat cecal content (t(50)), percent of drug released in 24 h in the presence of rat cecal content (Y(24) with RC). Transformed values of independent and dependent variables were subjected to multiple regressions to establish a full-model second-order polynomial equation. F was calculated to confirm the omission of insignificant terms from the full-model equation. The computer optimization process and contour plots predicted the levels of independent variables X(1), X(2), and X(3) (0, 0.2 and -0.15, respectively) for colon targeting and total percent of drug released up to 24 h.

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

    Directory of Open Access Journals (Sweden)

    Fernando Marcuz Silva

    2002-02-01

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

  17. Mesalazine sustained-release granules taking once daily or multi-times daily in the treatment of mild to moderate active ulcerative colitis:a randomised controlled clinical trial%美沙拉秦缓释颗粒剂顿服与分次服用治疗轻中度溃疡性结肠炎的临床随机对照研究

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    目的:观察美沙拉秦缓释颗粒剂顿服与分次服用治疗轻中度活动期 UC 的疗效、安全性和依从性。方法将60例轻中度活动期 UC 患者分为 A 、B 、C 3组,每组20例,A 组给予美沙拉秦缓释颗粒剂4 g/次,1次/d ;B 组为2 g/次,2次/d ;C 组为1 g/次,4次/d ,疗程8周。监测患者第0、4、8周的生命体征、Mayo 评分、依从性和不良反应。第0、8周行结肠镜检查。疗效评估的指标为临床完全缓解率、临床缓解率、有效率、黏膜愈合率、症状缓解时间和安全性。组间比较采用 F 检验、t 检验或卡方检验。结果 A 、B 、C 组的临床完全缓解率分别为20%(4/20)、10%(2/20)和10%(2/20),临床缓解率分别为70%(14/20)、65%(13/20)和70%(14/20),有效率分别为95%(19/20)、85%(17/20)和90%(18/20),黏膜愈合率分别为70%(14/20)、60%(12/20)和50%(10/20),不良反应发生率分别为20%(4/20)、15%(3/20)和20%(4/20),各组间差异均无统计学意义(P均>0.05)。 A 、B 组症状缓解时间分别为(15.4±3.7)和(15.6±2.9) d ,均短于 C 组的(18.4±3.6) d ,差异均有统计学意义(t =2.661、2.710, P均<0.05)。 A 、B 、C 组间性别、病程、严重程度、病变部位、疾病分型的亚组间临床缓解率比较,差异均无统计学意义(P均>0.05)。结论美沙拉秦缓释颗粒剂顿服与分次服用治疗轻中度活动期 UC 具有相似的疗效及安全性,顿服具有更好的依从性。%Objective To investigate the efficacy ,safety and compliance of mesalazine sustained‐release (SR) granules taking once daily or multi‐times daily in the treatment of patients with mild to moderate active ulcerative colitis .Methods Sixty patients with mild to moderate active ulcerative colitis were divided

  18. 肠炎康联合美沙拉嗪治疗溃疡性结肠炎效果分析%Analyze the Effect of Changyankang Combined With Mesalamine in the Treatment of Ulcerative Colitis

    Institute of Scientific and Technical Information of China (English)

    陈超

    2015-01-01

    目的:探讨肠炎康联合美沙拉嗪治疗溃疡性结肠炎的临床疗效。方法将60例溃疡性结肠炎患者按照住院先后顺序分为观察组(肠炎康+美沙拉嗪)与对照组(美沙拉嗪)。对比分析两组患者的临床治疗效果。结果观察组治疗总有效率高于对照组(P<0.05);观察组不良反应发生率低于对照组(P<0.05)。结论肠炎康联合美沙拉嗪治疗溃疡性结肠炎有着较好的临床效果。%Objective To explore the investigate the clinical effect of changyankang combined with mesalamine in the treatment of ulcerative colitis. Methods The 60 cases the patients with ulcerative colitis were randomly divided into treatment group (changyankang+mesalamine) and control group (mesalamine) according to the time of required hospitalization, and analysis comparative clinical effect of two groups. Results The total effective rate of treatment group was higher than control group (P<0.05). The incidence of adverse reactions in the study group was lower than control group (P<0.05). Conclusion Changyankang combined with mesalamine in the treatment of ulcerative colitis, it has a good clinical effect.

  19. New developments in the treatment of rosacea - role of once-daily ivermectin cream.

    Science.gov (United States)

    Cardwell, Leah A; Alinia, Hossein; Moradi Tuchayi, Sara; Feldman, Steven R

    2016-01-01

    Rosacea is a chronic dermatological disorder with a variety of clinical manifestations localized largely to the central face. The unclear etiology of rosacea fosters therapeutic difficulty; however, subtle clinical improvement with pharmacologic treatments of various drug categories suggests a multifactorial etiology of the disease. Factors that may contribute to disease pathogenesis include immune abnormality, vascular abnormality, neurogenic dysregulation, presence of cutaneous microorganisms, UV damage, and skin barrier dysfunction. The role of ivermectin in the treatment of rosacea may be as an anti-inflammatory and anti-parasitic agent targeting Demodex mites. In comparing topical ivermectin and metronidazole, ivermectin was more effective; this treatment modality boasted more improved quality of life, reduced lesion counts, and more favorable participant and physician assessment of disease severity. Patients who received ivermectin 1% cream had an acceptable safety profile. Ivermectin is efficacious in decreasing inflammatory lesion counts and erythema.

  20. Once-daily glycopyrronium bromide, a long-acting muscarinic antagonist, for chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Ulrik, Charlotte Suppli

    2012-01-01

    Long-acting bronchodilators are central in the pharmacological management of patients with chronic obstructive pulmonary disease (COPD). The aim of this systematic review is to provide an overview of the studies evaluating the safety and clinical efficacy of inhaled glycopyrronium bromide, a novel...

  1. Clinical efficacy, safety, and tolerability of once-daily fesoterodine in subjects with overactive bladder.

    Science.gov (United States)

    Chapple, Christopher; Van Kerrebroeck, Philip; Tubaro, Andrea; Haag-Molkenteller, Cornelia; Forst, Hans-Theo; Massow, Ute; Wang, Joseph; Brodsky, Marina

    2007-10-01

    To determine the efficacy, tolerability, and safety of fesoterodine in subjects with overactive bladder (OAB). This was a multicentre, randomised, double-blind, placebo- and active-controlled trial with tolterodine extended release (ER) to assess the efficacy and safety of fesoterodine. Eligible subjects (> or =18 yr) with increased micturition frequency and urgency and/or urgency urinary incontinence (UUI) were randomised to placebo, fesoterodine 4 mg, fesoterodine 8 mg, or tolterodine ER 4 mg for 12 wk. The primary efficacy variable was a change from baseline to week 12 in micturitions per 24 h. Co-primary end points included change from baseline to week 12 in UUI episodes per 24 h and Treatment Response ("yes" or "no," based on four-point treatment benefit scale). Secondary efficacy variables included mean volume voided per micturition, continent days per week, and number of urgency episodes. At the end of treatment, subjects taking fesoterodine 4 and 8 mg had significant (pfesoterodine 8 mg at most end points. Both doses of fesoterodine were significantly better than placebo in improving the symptoms of OAB and produced a significantly greater Treatment Response versus placebo. Efficacy was more pronounced with fesoterodine 8 mg compared with the other treatments. Active treatments were well tolerated.

  2. Profile of glycopyrronium for once-daily treatment of moderate-to-severe COPD [Corrigendum

    Directory of Open Access Journals (Sweden)

    Buhl R

    2014-03-01

    Full Text Available Buhl R, Banerji D. Int J Chron Obstruct Pulmon Dis. 2012;7:729–741. On page 737 in the first paragraph of the "Safety" section, the final sentence "Serious adverse events occurred with a slightly lower frequency in the glycopyrronium treatment group (11% compared with placebo (13% and the tiotropium group (15%, Table 3.32,33" should read "Serious adverse events occurred with a slightly lower frequency in the glycopyrronium treatment group (10% compared with placebo (13% and the tiotropium group (15%, Table 3.32,33"Read the original article 

  3. Using Six Sigma to improve once daily gentamicin dosing and therapeutic drug monitoring performance.

    LENUS (Irish Health Repository)

    Egan, Sean

    2012-08-07

    BACKGROUND: Safe, effective therapy with the antimicrobial gentamicin requires good practice in dose selection and monitoring of serum levels. Suboptimal therapy occurs with breakdown in the process of drug dosing, serum blood sampling, laboratory processing and level interpretation. Unintentional underdosing may result. This improvement effort aimed to optimise this process in an academic teaching hospital using Six Sigma process improvement methodology. METHODS: A multidisciplinary project team was formed. Process measures considered critical to quality were defined, and baseline practice was examined through process mapping and audit. Root cause analysis informed improvement measures. These included a new dosing and monitoring schedule, and standardised assay sampling and drug administration timing which maximised local capabilities. Three iterations of the improvement cycle were conducted over a 24-month period. RESULTS: The attainment of serum level sampling in the required time window improved by 85% (p≤0.0001). A 66% improvement in accuracy of dosing was observed (p≤0.0001). Unnecessary dose omission while awaiting level results and inadvertent disruption to therapy due to dosing and monitoring process breakdown were eliminated. Average daily dose administered increased from 3.39 mg\\/kg to 4.78 mg\\/kg\\/day. CONCLUSIONS: Using Six Sigma methodology enhanced gentamicin usage process performance. Local process related factors may adversely affect adherence to practice guidelines for gentamicin, a drug which is complex to use. It is vital to adapt dosing guidance and monitoring requirements so that they are capable of being implemented in the clinical environment as a matter of routine. Improvement may be achieved through a structured localised approach with multidisciplinary stakeholder involvement.

  4. Role of once-daily glycopyrronium bromide (NVA237 in the management of COPD

    Directory of Open Access Journals (Sweden)

    D’Urzo A

    2013-08-01

    Full Text Available Anthony D'UrzoDepartment of Family and Community Medicine, University of Toronto, Toronto, ON, CanadaAbstract: Progressive airflow limitation is a hallmark feature of chronic obstructive pulmonary disease (COPD that ultimately leads to breathlessness, impaired quality of life, and reduced exercise capacity. Pharmacotherapy is used in patients with COPD to prevent and control symptoms, reduce both the frequency and severity of exacerbations, improve health status, and increase exercise tolerance. These strategies are intended to address management issues which promote both current disease control and a reduction in the risk of disease deterioration in the future. At the present time, long-acting β2-agonists (LABAs and long-acting muscarinic antagonists (LAMAs are available for maintenance therapy in patients with persistent symptoms. Tiotropium was the first LAMA to be approved for management of COPD, and many studies have described its beneficial effects on multiple clinically relevant outcomes. Glycopyrronium bromide (NVA237, a new LAMA, has been developed and received regulatory approval for management of COPD in a number of countries around the world. Results from pivotal Phase III trials suggest that NVA237 is safe and well tolerated in patients with moderate to severe COPD, and provides rapid and sustained improvements in lung function. Further, these changes are associated with statistically and clinically meaningful improvements in dyspnea, health-related quality of life, and exercise tolerance. Treatment with NVA237 also results in a significant reduction in risk of exacerbations and the need for rescue medication, and has been comparable with tiotropium with respect to safety and efficacy outcomes. Finally, emerging data indicate that NVA237 is efficacious both as monotherapy and in combination with indacaterol.Keywords: glycopyrronium bromide, NVA237, chronic obstructive pulmonary disease, inhaled long-acting bronchodilators

  5. New developments in the treatment of rosacea – role of once-daily ivermectin cream

    Science.gov (United States)

    Cardwell, Leah A; Alinia, Hossein; Moradi Tuchayi, Sara; Feldman, Steven R

    2016-01-01

    Rosacea is a chronic dermatological disorder with a variety of clinical manifestations localized largely to the central face. The unclear etiology of rosacea fosters therapeutic difficulty; however, subtle clinical improvement with pharmacologic treatments of various drug categories suggests a multifactorial etiology of the disease. Factors that may contribute to disease pathogenesis include immune abnormality, vascular abnormality, neurogenic dysregulation, presence of cutaneous microorganisms, UV damage, and skin barrier dysfunction. The role of ivermectin in the treatment of rosacea may be as an anti-inflammatory and anti-parasitic agent targeting Demodex mites. In comparing topical ivermectin and metronidazole, ivermectin was more effective; this treatment modality boasted more improved quality of life, reduced lesion counts, and more favorable participant and physician assessment of disease severity. Patients who received ivermectin 1% cream had an acceptable safety profile. Ivermectin is efficacious in decreasing inflammatory lesion counts and erythema. PMID:27051311

  6. Once-Daily Amikacin Dosing in Burn Patients Treated with Continuous Venovenous Hemofiltration

    Science.gov (United States)

    2011-10-01

    previously documented inaccuracies with the Vitek 2 instrument (1), all Acinetobacter baumannii isolates reported as susceptible to amikacin were confirmed...64 Acinetobacter baumannii (35) 39.1% 23 64/64 Other Enterobacteriaciae (43) Stenotrophomonas maltophilia (11), Enterobacter aerogenes (9...al. 2010. Aminoglycoside resistance and susceptibility testing errors in Acinetobacter baumannii -calcoaceticus complex. J. Clin. Microbiol. 48:1132

  7. Clinical potential of lixisenatide once daily treatment for type 2 diabetes mellitus

    DEFF Research Database (Denmark)

    Petersen, Andreas Brønden; Christensen, Mikkel

    2013-01-01

    The glucagon-like peptide (GLP)-1 receptor agonist lixisenatide (Lyxumia(®)) was approved for marketing by the European Medicines Agency in February 2013 and has been evaluated in a clinical study program called GetGoal. Lixisenatide activates the GLP-1 receptor and thereby exercises the range of...... of lixisenatide seems to be in combination with basal insulin. A large multicenter study will determine the future potential of lixisenatide in preventing cardiovascular events and mortality, in patients with type 2 diabetes and recent acute coronary syndrome.......The glucagon-like peptide (GLP)-1 receptor agonist lixisenatide (Lyxumia(®)) was approved for marketing by the European Medicines Agency in February 2013 and has been evaluated in a clinical study program called GetGoal. Lixisenatide activates the GLP-1 receptor and thereby exercises the range...

  8. Once daily levocetirizine for the treatment of allergic rhinitis and chronic idiopathic urticaria

    Directory of Open Access Journals (Sweden)

    E Nettis

    2008-12-01

    Full Text Available E Nettis1, G F Calogiuri2, E Di Leo1, F Cardinale3, L Macchia1, A Ferrannini1, A Vacca1,41Section of Allergology and Clinical Immunology, Department of Internal Medicine and Infectious Diseases; 24th Pneumology Department, Pneumologic Hospital A Galateo, San Cesario di Lecce, Italy; 3Department of Biomedicina dell’Età Evolutiva, Pediatrics Unit “S Maggiore”; 4Department of Internal Medicine and Clinical Oncology, University of Bari Medical School, Bari, ItalyAbstract: Levocetirizine is the pharmacologically active enantiomer of cetirizine. It is a potent histamine H-1 receptor antagonist with anti-inflammatory and antiallergic properties. The review analyses the levocetirizine’s properties in terms of safety and efficacy both in allergic rhinitis and urticarioid syndromes.Keywords: allergic rhinitis, chronic idiopatic urticaria, levocetirizine

  9. New developments in the treatment of rosacea – role of once-daily ivermectin cream

    Directory of Open Access Journals (Sweden)

    Cardwell LA

    2016-03-01

    Full Text Available Leah A Cardwell,1 Hossein Alinia,1 Sara Moradi Tuchayi,1 Steven R Feldman,1–31Department of Dermatology, Center for Dermatology Research, 2Department of Pathology, 3Department of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA Abstract: Rosacea is a chronic dermatological disorder with a variety of clinical manifestations localized largely to the central face. The unclear etiology of rosacea fosters therapeutic difficulty; however, subtle clinical improvement with pharmacologic treatments of various drug categories suggests a multifactorial etiology of the disease. Factors that may contribute to disease pathogenesis include immune abnormality, vascular abnormality, neurogenic dysregulation, presence of cutaneous microorganisms, UV damage, and skin barrier dysfunction. The role of ivermectin in the treatment of rosacea may be as an anti-inflammatory and anti-parasitic agent targeting Demodex mites. In comparing topical ivermectin and metronidazole, ivermectin was more effective; this treatment modality boasted more improved quality of life, reduced lesion counts, and more favorable participant and physician assessment of disease severity. Patients who received ivermectin 1% cream had an acceptable safety profile. Ivermectin is efficacious in decreasing inflammatory lesion counts and erythema. Keywords: papulopustular rosacea, topical ivermectin, metronidazole, azelaic acid, topical

  10. Efficacy and safety of pretransplant conditioning regimens with intravenous infusion of busulfan once daily and cyclophosphamide in patients undergoing allogeneic stem cell transplantation%异基因造血干细胞移植患者白消安每日一次静脉滴注联合环磷酰胺预处理方案的疗效及安全性

    Institute of Scientific and Technical Information of China (English)

    冀冰心; 苏力; 赵弘; 惠吴函; 孙婉玲; 徐娟

    2013-01-01

    目的 评价异基因造血干细胞移植(Allo-HSC)治疗中应用白消安每日1次静脉滴注联合环磷酰胺预处理方案的疗效和安全性. 方法 收集首都医科大学宣武医院2004年1月至2012年6月以白消安/环磷酰胺(Bu/Cy)为预处理方案进行Allo-HSC治疗连续病例的病历资料进行回顾性分析.将患者分为口服组[2004年1月至2006年6月住院患者,口服白消安4.0 mg/(kg·d),共3 d]和静脉组[2006年7月至2012年6月住院患者,静脉滴注白消安3.2 mg/(kg·d),共3 d].记录2组患者不良反应发生率、造血功能重建情况及生存率. 结果 共收集到患者50例,静脉组34例,口服组16例.2组患者性别、年龄、输入细胞数差异无统计学意义(P>0.05).静脉组患者口腔黏膜炎、胃肠道反应、肝损害发生率均明显低于口服组[11.7% (4/34)比43.8% (7/16),17.6% (6/34)比50.0%(8/16),20.6%(7/34)比50.0%(8/16),均P<0.05];未发现肝静脉闭塞病及癫痫等不良反应发生.静脉组和口服组患者均获得造血重建,2组外周血中性粒细胞计数≥0.5×109/L和血小板计数≥20×109/L所需时间差异无统计学意义[(14.3 ±3.5)d比(15.6±4.0)d,(17.5±5.0)d比(19.0±6.7)d,均P>0.05].静脉组和口服组患者5年生存率分别为(69.5±12.1)%和(62.5±12.1)%,组间差异无统计学意义(P>0.05). 结论 恶性血液病的Allo-HSC治疗中预处理方案采用白消安每日1次静脉滴注联合环磷酰胺较口服白消安有更好的安全性,而且疗效确切.%Objective To evaluate the efficacy and safety of pretransplant conditioning regimens with intravenous (Ⅳ) infusion of busulfan once daily and cyclophosphamide in patients undergoing allogeneic stem cell transplantation allo-HSCT.Methods The data of consecutive patients treated with a conditioning regimen with busulfan and cyclophosphamide (Bu/Cy) before undergoing allo-HSCT in Xuanwu Hospital of Capital Medical University from January 2004 to June

  11. EFFECT OF LUMINAL pH CHANGES ON GUAR GUM-HPMC E15 LV MIXED MATRIX TABLETS FOR MESALAMINE DRUG DELIVERY TO COLON AND STUDY ON IN- VITRO CHARACTERISTICS IN TWO DIFFERENT DISSOLUTION MODELS vs. MARKETED FORMULATION

    Directory of Open Access Journals (Sweden)

    A. Maria John Newton*, L. Prabakaran and K.N. Jayaveera

    2012-07-01

    Full Text Available The study was designed to investigate the impact of colonic pH changes on formulated colon targeted Mesalamine matrix tablets in the treatment of inflammatory bowel disease (IBD. Mesalamine tablets were fabricated with guar gum as Polymer system. The different batches of Mesalamine tablets (GMM1-GMM6 were compressed with increasing proportion of guar gum and HPMC E15 LV. The different buffer conditions were chosen to mimic the pH changes in terminal part of the ileum as well as the colon. A separate two in vitro studies were conducted in all the formulations. The impact of the pH changes on the coated tablets in normal pH condition and reduced pH condition (pH reduced during IBD were compared. In IBD the pH of the colon falls below its normal level. The extent of pH change depends on the severity of the disease. The study was designed to evaluate the in vitro dissolution characteristics of Mesalamine matrix tablets in a variety of simulated fluids (pH range 1.2, 6, 6.8, 7.2, 5. The results indicated that the impact of pH changes on drug release profile was not affected in the diseased and normal pH condition of the colon. The present treatment methods of IBD mostly depend on pH sensitivity polymers or enteric coating technique. These pH sensitive polymers based colonic devices may not serve the patient needs successfully because the influence of colonic pH on pH sensitive polymer based devices plays an important role in triggering the drug release in target site. The lowered pH condition in diseased state could not trigger the drug release in pH sensitive polymer based devices as it was not the threshold pH of the particular coated polymer. In case of enteric coating there may be a possibility of disintegration of the tablet before reaching the colon due to the contractile movement of GI tract and fluctuation in the GI pH. The present matrix tablets were prepared with guar gum, which cannot be affected by the pH changes of the colon, maintained

  12. 美沙拉嗪栓剂治疗溃疡性结肠炎的效果研究%Observation on Mesalamine Suppository Application Efficacy in Treatment of Ulcerative Colitis

    Institute of Scientific and Technical Information of China (English)

    邵丽

    2015-01-01

    Objective Clinical efficacy of mesalamine suppository in treatment of ulcerative colitis is to be investigated. Methods Choose 36 ulcerative colitis patients who are treated in hospital from April 2013 to April 2014,patients in control group are given mesalamine enteric-coated tablets treatment;while patients in study group are given additional mesalamine suppository treatment,and then observe and compare treatment efficacy in these two groups. Results Treatment efficacy(92.86%)and mucosal disease remission rate(92.86%)in study group are higher than counterparts in control group(81.82%),(77.27%); there is differential between study group and such a differential has statistic value(P<0.05). Conclusion Mesalamine suppository is of efficacy in treatment of ulcerative colitis;it is conducive to increasing intestinal medicine concentration,shortening treatment course and preventing from side effect with safety;therefore,such a treatment method is quite worthwhile to be promoted widespread.%目的:研究溃疡性结肠炎应用美沙拉嗪栓剂治疗的临床疗效。方法选取我院2013年4月~2014年4月间收治的36例溃疡性结肠炎患者,对照组接受美沙拉嗪肠溶片口服治疗,治疗组同时接受美沙拉嗪栓剂治疗,比较两组临床疗效。结果治疗组总有效率(92.86%)、黏膜病变缓解率(92.86%)与对照组(81.82%)、(77.27%)相比较高,两组患者临床疗效差异显著,有统计学意义(P<0.05)。结论溃疡性结肠炎应用美沙拉嗪栓剂治疗能够增加肠道药物浓度,缩短康复进程,预防不良反应,安全性高,值得推广。

  13. Randomised clinical trial: evaluation of the efficacy of mesalazine (mesalamine) suppositories in patients with ulcerative colitis and active rectal inflammation -- a placebo-controlled study.

    Science.gov (United States)

    Watanabe, M; Nishino, H; Sameshima, Y; Ota, A; Nakamura, S; Hibi, T

    2013-08-01

    Mesalazine suppositories are recommended and widely used as the standard therapy in induction and maintenance of remission for proctitis. To evaluate the efficacy of mesalazine suppositories in patients with ulcerative colitis (UC) and rectal inflammation; and in patient groups categorised by the extent of lesions. This study was a phase III multicentre, randomised, double-blind, placebo-controlled, parallel-group study. Mild-to-moderate UC patients with rectal inflammation were randomly assigned either a 1 g mesalazine or placebo suppository. The suppository was administered in the rectum once daily for 4 weeks. The primary efficacy end point was the rate of endoscopic remission (mucosal score of 0 or 1) after 4 weeks. The endoscopic remission rates after 4 weeks in the mesalazine and placebo suppository groups were 81.5% and 29.7%, respectively, and the superiority of mesalazine to placebo was confirmed (P suppository groups, respectively, and the corresponding rates for all other types of UC were 78.6% and 21.4%, respectively. The superiority of mesalazine to placebo was confirmed in both subgroups (P suppositories in all types of UC patients with rectal inflammation was confirmed for the first time in a double-blind, placebo-controlled, parallel-group study (JapicCTI- 111421). © 2013 John Wiley & Sons Ltd.

  14. Delayed-Release Oral Mesalamine 4.8 g/day (800 mg tablets Compared with 2.4 g/day (400 mg tablets for the Treatment of Mildly to Moderately Active Ulcerative Colitis: The ASCEND I Trial

    Directory of Open Access Journals (Sweden)

    Stephen B Hanauer

    2007-01-01

    Full Text Available BACKGROUND: Delayed-release oral mesalamine 2.4 g/day to 4.8 g/day has been shown to be effective in treating mildly to moderately active ulcerative colitis (UC, but it is unknown whether an initial dose of 4.8 g/day is more effective than 2.4 g/day in patients with mildly to moderately active UC and in the subgroup with moderate disease.

  15. Assessment of efficacy and tolerability of once-daily extended release metformin in patients with type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Levy Juliana

    2010-03-01

    Full Text Available Abstract Aims To determine prospectively the efficacy, tolerability and patient satisfaction of an extended release formulation of metformin (metformin XR in hospital based outpatients with type 2 diabetes mellitus currently treated with standard metformin. Methods Patients on immediate release standard metformin either alone or combined with other oral agents were switched to extended release metformin XR 500 mg tablets and titrated to a maximum dose of 2000 mg/day Measurements to include glucose and lipid control, blood pressure, body weight, waist circumference, C-reactive protein, adverse events and patient satisfaction were recorded at baseline, three and six months. Results Complete data were obtained for 35 of the 61 patients enrolled to the study. At three and six months no changes were reported for any of the cardiovascular risk factors except for lipids where there was a modest rise in plasma triglycerides. These effects were achieved with a reduced dose of metformin XR compared to pre-study dosing with standard metformin (1500 mg +/- 402 vs 1861 +/- 711 p = 0.004. A total of 77% of patients were free of gastrointestinal side effects and 83% of patients stated a preference for metformin XR at the end of the study. Ghost tablets were reported in the faeces by the majority of the patients (54.1%. Conclusions Patients switched to extended release metformin XR derived the same clinical and metabolic benefits as for standard metformin but with reduced dosage, fewer gastrointestinal side effects and a greater sense of well being and satisfaction on medication.

  16. Efficacy and safety of duloxetine 60 mg once daily in major depressive disorder: a review with expert commentary

    Directory of Open Access Journals (Sweden)

    Susan G Ball

    2013-01-01

    Full Text Available Objective: Major depressive disorder (MDD is a significant public health concern and challenges health care providers to intervene with appropriate treatment. This article provides an overview of efficacy and safety information for duloxetine 60 mg/day in the treatment of MDD, including its effect on painful physical symptoms (PPS.Design: A literature search was conducted for articles and pooled analyses reporting information regarding the use of duloxetine 60 mg/day in placebo-controlled trials.Setting: Placebo-controlled, active-comparator, short- and long-term studies were reviewed.Participants: Adult (≥18 years patients with MDD.Measurements: Effect sizes for continuous outcome (change from baseline to endpoint and categorical outcome (response and remission rates were calculated using the primary measures of 17-item Hamilton Rating Scale for Depression (HAMD-17 or Montgomery–Åsberg Depression Rating Scale (MADRS total score. The Brief Pain Inventory and Visual Analogue Scales were used to assess improvements in PPS. Glass estimation method was used to calculate effect sizes, and numbers needed to treat (NNT were calculated based on HAMD-17 and MADRS total scores for remission and response rates. Safety data were examined via the incidence of treatment-emergent adverse events and by mean changes in vital-sign measures.Results: Treatment with duloxetine was associated with small-to-moderate effect sizes in the range of 0.12 to 0.72 for response rate and 0.07 to 0.65 for remission rate. NNTs were in the range of 3 to 16 for response and 3 to 29 for remission. Statistically significant improvements (p≤0.05 were observed in duloxetine-treated patients compared to placebo-treated patients in PPS and quality of life. The safety profile of the 60-mg dose was consistent with duloxetine labeling, with the most commonly observed significant adverse events being nausea, dry mouth, diarrhea, dizziness, constipation, fatigue, and decreased appetite.Conclusion: These results reinforce the efficacy and tolerability of duloxetine 60 mg/day as an effective short- and long-term treatment for adults with MDD. The evidence of the independent analgesic effect of duloxetine 60 mg/day supports its use as a treatment for patients with PPS associated with depression. This review is limited by the fact that it included randomized clinical trials with different study designs. Furthermore, data from randomized controlled trials may not generalize well to real clinical practice.

  17. Efficacy of once-daily indacaterol relative to alternative bronchodilators in COPD: a patient-level mixed treatment comparison.

    Science.gov (United States)

    Cope, Shannon; Capkun-Niggli, Gorana; Gale, Rupert; Lassen, Cheryl; Owen, Roger; Ouwens, Mario J N M; Bergman, Gert; Jansen, Jeroen P

    2012-05-01

    Indacaterol was evaluated versus placebo, formoterol, and salmeterol in randomized controlled trials. No direct comparisons, however, are available for indacaterol 150 μg with formoterol or indacaterol 300 μg with salmeterol. Indacaterol trial evidence was synthesized to provide coherent estimates of indacaterol 150 μg and indacaterol 300 μg relative to formoterol, salmeterol, and tiotropium. Four randomized controlled trials were combined with Bayesian mixed treatment comparisons by using individual patient-level data. End points of interest were trough forced expiratory volume in 1 second (FEV(1)), St. George's Respiratory Questionnaire (SGRQ) total score and response (≥ 4 points), and Transition Dyspnea Index total score and response (≥ 1 point). Indacaterol 150 μg demonstrated a higher FEV(1) than did formoterol at 12 weeks and 6 months (0.10 L difference; 95% credible interval [CrI] = 0.06-0.14), as did indacaterol 300 μg versus salmeterol (0.06 L difference at 12 weeks; CrI = 0.02-0.10; 0.06 L at 6 months; CrI = 0.02-0.11). Regarding SGRQ, indacaterol 150 μg demonstrated a comparable proportion of responders versus formoterol, as did indacaterol 300 μg versus salmeterol. In comparison to tiotropium, indacaterol 150 μg demonstrated a greater proportion of responders (odds ratio = 1.52 at 12 weeks; CrI 1.15-2.00). For Transition Dyspnea Index, indacaterol 150 μg and formoterol showed a similar response. Indacaterol 300 μg was more efficacious than salmeterol (odds ratio = 1.65 at 12 weeks; CrI 1.16-2.34). Overall, indacaterol 150 μg showed the greatest efficacy for SGRQ and indacaterol 300 μg for FEV(1) and Transition Dyspnea Index. Indacaterol is expected to be comparable to formoterol, salmeterol, and tiotropium, providing higher FEV(1) than formoterol and salmeterol and greater improvement in the SGRQ total score than tiotropium. Indacaterol 150 μg provided comparable improvement in dyspnea, while indacaterol 300 μg demonstrated the greatest response overall. Copyright © 2012 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

  18. Insulin degludec, a long-acting once-daily basal analogue for type 1 and type 2 diabetes mellitus.

    Science.gov (United States)

    Berard, Lori; MacNeill, Gail

    2015-02-01

    Here, we discuss certain practical issues related to use of insulin degludec, a new long-acting basal insulin analogue. Degludec provides uniform ("peakless") action that extends over more than 24 hours and is highly consistent from dose to dose. Like the 2 previously available basal analogues (detemir and glargine), degludec is expected to simplify dose adjustment and enable patients to reach their glycemic targets with reduced risk of hypoglycemia. Phase 3 clinical trials involving type 1 and type 2 diabetes have demonstrated that degludec was noninferior to glargine in allowing patients to reach a target glycated hemoglobin (A1C) of 7%, and nocturnal hypoglycemia occurred significantly less frequently with degludec. In addition, when dosing intervals vary substantially from day to day, degludec continues to be effective and to maintain a low rate of nocturnal hypoglycemia. Degludec thus has the potential to reduce risk of nocturnal hypoglycemia, to enhance the flexibility of the dosing schedule and to improve patient and caregiver confidence in the stability of glycemic control. A dedicated injector, the FlexTouch prefilled pen, containing degludec 200 units/mL, will be recommended for most patients with type 2 diabetes. Degludec will also be available as 100 units/mL cartridges, to be used in the NovoPen 4 by patients requiring smaller basal insulin doses, including most patients with type 1 diabetes.

  19. A comparison of roxatidine acetate 150 mg once daily and 75 mg twice daily in gastric ulcer healing.

    Science.gov (United States)

    Rösch, W

    1988-01-01

    In 363 outpatients with endoscopically confirmed gastric ulcers the efficacy and safety of roxatidine acetate 150 mg at night was compared to 75 mg twice daily. After 8 weeks' treatment substantial reductions in gastric ulcer diameter were obtained in addition to healing rates of 83.7 and 86% for the twice daily and night-time dosing, respectively. Daily reductions in day and night-time epigastric pain were obtained with no significant differences between treatment groups for pain scores or antacid tablet consumption. Furthermore, cigarette smoking did not influence the healing rates produced by either treatment schedule. 26 patients reported 32 adverse reactions and 5 patients discontinued treatment because of side effects, although only 1 of these was a severe reaction. The present data suggest that a single night-time dose of roxatidine acetate 150 mg is as safe and effective as the twice daily dose regimen for the management of acute gastric ulceration.

  20. A comparison of roxatidine acetate 150 mg once daily and 75 mg twice daily in duodenal ulcer healing.

    Science.gov (United States)

    Hentschel, E; Schütze, K

    1988-01-01

    A randomised multicentre, double-blind study of the efficacy and safety of roxatidine acetate 150 mg at bedtime or 75 mg twice a day was conducted in 300 outpatients with endoscopically confirmed duodenal ulcers. After 14 days' treatment with roxatidine acetate substantial reductions in ulcer sizes had been obtained, in addition to healing rates of 87 to 89%, with no significant differences between the dosage regimens. There were graded reductions in day and night-time assessment of epigastric pain for both treatment groups and no differences in the mean numbers of antacid tablets consumed. In addition, cigarette smoking did not influence the healing rates produced by either treatment schedule. 11 patients reported 12 mild adverse reactions, with gastrointestinal symptoms the most frequent, and no clinically significant alterations in laboratory values. The present data suggests that a single bedtime dose of roxatidine acetate 150 mg produces effective duodenal ulcer healing and pain relief equivalent to that produced by a twice daily dosage regimen.

  1. Benefits of once-daily administration of cyclosporine a for children with steroid-dependent, relapsing nephrotic syndrome.

    Science.gov (United States)

    Suzuki, Koichi; Oki, Eishin; Tsuruga, Kazushi; Aizawa-Yashiro, Tomomi; Ito, Etsuro; Tanaka, Hiroshi

    2010-03-01

    Cyclosporine A (CsA) is an effective steroid-sparing agent for patients with steroid-dependent, relapsing nephrotic syndrome (SDRNS). The efficacy and safety of single-daily dose administration (SDD protocol) of CsA in selected patients with SDRNS has been reported. However, the efficacy of initial CsA treatment for children with SDRNS using the SDD protocol remains to be elucidated. The SDD protocol might be associated with lower clinical toxicity, compared to the conventional twice-daily dose administration (TDD protocol). Here we evaluated the efficacy and safety of the SDD protocol versus the TDD protocol in patients with SDRNS. The data from 19 patients (9.9 +/- 4.2 years old) were retrospectively collected and analyzed. Ten patients treated according to the SDD protocol for a mean of 27 months (SDD group), while 9 patients treated with the TDD protocol for a mean of 35 months (TDD group) as an initial CsA treatment. Although the mean daily CsA dose was significantly lower in the SDD group (1.5 +/- 0.4 mg/kg/day vs. 3.7 +/- 0.7 mg/kg/day, P SDD group showed nephrotoxicity. Despite a small number of patients, this study may support that the SDD protocol is at least as effective as the conventional TDD protocol, and is more cost-effective for selected children with SDRNS.

  2. The economics of 4 grams once daily mesalazine dosing compared with 4 grams twice daily in active ulcerative colitis

    NARCIS (Netherlands)

    Connolly, M.; Kuyvenhoven, J.; Postma, M.; Nielsen, S.

    2013-01-01

    Background: Dosing frequency is an important treatment consideration that has been shown to influence adherence and outcomes when treating ulcerative colitis (UC). In this analysis we evaluate the economic consequences of outcome differences observed in the study comparing mesalazine 4g per day once

  3. Tadalafil once daily: Narrative review of a treatment option for female sexual dysfunctions (FSD in midlife and older women

    Directory of Open Access Journals (Sweden)

    Chiara Borghi

    2017-03-01

    Full Text Available Female Sexual Disorders (FSD include a complex, multidimensional, individual experience that can change as an individual age, suggesting that these problems are caused by multiple factors including psychosocial factors, personal relationships, pathologic changes caused by diseases, and pharmacologic influences. Menopause is an important time for middle aged women and postmenopausal physiological changes could have a significant role in the development of FSD. Few is still known about their correct definition and treatment. Their incidence, prevalence and risk factors are difficult to define because of a high level of overlap in the experience of problems with desire, arousal, and orgasm. Little evidences are known about the best therapeutic approach, and both non-pharmacological and pharmacological treatment options have been described. Among these, phosphodiesterase type 5 inhibitors could be an effective option for many subtypes of female sexual disorders, with an improvement in different aspects of sexual function, such as desire, arousal, orgasm and sexual satisfaction. In this paper authors reviewed what is already known about the use of these vasoactive agents, particularly tadalafil, as a treatment option for female sexual disturbances.

  4. Effect comparison of mesalamine and sulfasalazine in the treatment of ulcerative colitis%美沙拉嗪与柳氮磺吡啶治疗溃疡性结肠炎的效果比较

    Institute of Scientific and Technical Information of China (English)

    刘德喜

    2015-01-01

    目的:比较美沙拉嗪与柳氮磺吡啶治疗溃疡性结肠炎的效果。方法选取安达市医院2012年8月—2014年8月收治的76例溃疡性结肠炎患者,根据入院顺序分为治疗组与对照组,每组38例。治疗组采用美沙拉嗪治疗,对照组采用柳氮磺吡啶治疗,比较两组的临床效果及不良反应发生情况。结果治疗组的总有效率高于对照组,不良反应发生率低于对照组,差异有统计学意义( P﹤0.05)。结论美沙拉嗪治疗溃疡性结肠炎的效果优于柳氮磺吡啶,且不良反应少。%Objective To comPare the effect of mesalamine and sulfasalazine in the treatment of ulcerative colitis. Methods From August 2012 to August 2014 in the HosPital of Anda City,a total of 76 Patients with ulcerative colitis were se-lected and divided into the treatment grouP and the control grouP by order of hosPitalization,38 cases in each grouP. The treat-ment grouP were treated with mesalazine,the control grouP were treated with sulfasalazine,clinical efficacy and adverse reac-tions between the two grouPs were comPared. Results The total effective rate of the treatment grouP was higher than that of the control grouP,the incidence of adverse reactions was lower than that of the control grouP,the differences were statistically signif-icant(P﹤0. 05). Conclusion Clinical efficacy of mesalamine is better than that of sulfasalazine in treating ulcerative colitis, and has fewer adverse reactions.

  5. Clinical Evaluation of Mesalamine Combined with Live Bacterial Agent of Bifidobacterium, Lactobacillus, Enterococcus and Bacillus Cereus for Ulcerative Colitis%美沙拉嗪联合双歧杆菌四联活菌治疗溃疡性结肠炎的临床效果评价

    Institute of Scientific and Technical Information of China (English)

    歧红阳; 王云溪; 肖占宇

    2011-01-01

    目的 研究美沙拉嗪联合双歧杆菌四联活菌在治疗溃疡性结肠炎中的临床效果。方法 选取50例溃疡性结肠炎病人,分为2组,试验组27例,给予美沙拉嗪及双歧杆菌四联活菌;对照组23例,给予美沙拉嗪。观察2组患者治愈率及治疗前后的患者血清中自细胞介素-8(IL-8)水平。结果 试验组治愈率(92.6%)明显高于对照组(78.3%),经比较差异有统计学意义(P<0.05),试验组和对照组治疗14 d后,IL-8水平明显低于治疗前,两者相比,差异有统计学意义(P<0.05)。结论 美沙拉嗪联合双歧杆菌四联活菌可提高溃疡性结肠炎的治愈率,且不良反应少,为临床治疗提供思路。%[Objective]To study the clinical effect of mesalamine combined with live bacterial agent of bifidobacterium, lactobacil-lus, enterococcus and bacillus cereus for ulcerative colitis. [ Methods ] 50 patients with ulcerative colitis were randomly divided into the research group (27 cases) and the control group (23 cases). The research group was given mesalamine combined with live bacterial agent of bifidobacterium, lactobacillus, enterococcus and bacillus cereus, and the control group was treated with mesalamine. The cure rate and IL-8 level in serum of patients before and after treatment were observed. [ Results ] The cure rate of the research group (92.6% ) was higher than that of the control group (78.3% ) significantly (P<0.05). After 14 days of treatment, and the IL-8 level of two groups was significantly lower than before treatment (P <0.05). [ Conclusion] Mesalamine combined with live bacterial agent of bifidobacterium, lactobacillus, enterococcus and bacillus cereus can improve the cure rate of ulcerative colitis, and with less adverse reaction, which provides a new idea for clinical therapy.

  6. 美沙拉嗪联合奥硝唑治疗溃疡性结肠炎的疗效观察%Efficacy of mesalamine combined ornidazole in treatment of ulcerative colitis

    Institute of Scientific and Technical Information of China (English)

    杨梅

    2014-01-01

    Objective To investigate the effect of mesalazine combined ornidazole in treatment of ulcerative colitis. Methods 80 patients with ulcerative colitis were randomly divided into observation group(mesalamine joint ornidazole treatment) and the control group(mesalamine treatment), 40 cases in each. The course was eight weeks, the clinical efficacy and DAI changes were compared before and after treatment. Results After treatment 8 weeks, the total efficiency of observation group was 95.0%,was significantly higher than the control group(77.5%)(x2=4.973, P0.05).After treatment 8 weeks, the DAI of two groups was significantly lowered than before treatment(t=2.37,2.89,P < 0.05), and the DAI of the observation group reduced more significantly than the control group(t=2.972, P < 0.05). Conclusion Mesalazine combined ornidazole in treatment of ulcerative colitis has good efficacy,is safety,and can significantly improve clinical symptoms, should be promoted and applied.%目的:探讨美沙拉嗪联合奥硝唑治疗溃疡性结肠炎的疗效。方法80例溃疡性结肠炎患者随机分为观察组(美沙拉嗪联合奥硝唑治疗)和对照组(美沙拉嗪治疗)各40例。连用8周,比较两组的临床疗效及治疗前后DAI的变化。结果治疗8周后,观察组患者的总有效率95.0%,明显高于对照组77.5%(x2=4.973, P<0.05)。治疗前两组DAI比较,差异无统计学意义(P>0.05)。治疗8周后,两组患者的DAI 明显均较治疗前明显降低(t=2.37、2.89,P<0.05),且观察组DAI较对照组降低更显著(t=2.972,P<0.05)。结论美沙拉嗪联合奥硝唑治疗溃疡性结肠炎疗效确切,安全性好,可以明显改善患者的临床症状,值得推广和应用。

  7. 双歧杆菌三联活菌联合美沙拉嗪治疗溃疡性结肠炎临床研究%Clinical Study of Bifidobacterium Triple Viable Bacteria with Mesalamine on Treating Ulcerative Colitis

    Institute of Scientific and Technical Information of China (English)

    许春进; 南君; 葛大赫

    2016-01-01

    目的:探讨双歧杆菌三联活菌联合美沙拉嗪治疗溃疡性结肠炎的临床效果。方法选取我院2014年2月~2016年2月收治的溃疡性结肠炎患者94例,随机分为两组,各47例。对照组给予美沙拉嗪治疗,观察组给予双歧杆菌三联活菌联合美沙拉嗪治疗,对比两组治疗有效率、治疗前后细胞因子水平和氧化应激水平。结果观察组总有效率高于对照组,差异有统计学意义(P<0.05);观察组治疗后TNF-α、IL-6、IL-8低于对照组,IL-10高于对照组,差异有统计学意义(P<0.05);观察组治疗后SOD高于对照组,MDA低于对照组,差异有统计学意义(P<0.05)。结论双歧杆菌三联活菌联合美沙拉嗪治疗溃疡性结肠炎可明显提高疗效,改善细胞因子水平和氧化应激水平。%Objective To investigate the clinical effect of triple viable Bifidobacterium combined with the Mesalamine in the treatment of ulcerative colitis.Methods 94 patients with ulcerative colitis in our hospital from February 2014 to February 2016 were randomly divided into two groups, 47 cases in each. The control group was given the salad diazoxide treatment, the observation group was given Biifd Triple Viable combined beauty The treatment of salad. Treatment efficiency, cytokine levels and oxidative stress levels before and after treatment were compared.Results The total effective rate of observation group was higher than the control group, the difference was significant (P< 0.05).The observation group after treatment, TNF-α,IL-6, IL-8 were lower than the control group, IL-10 was higher than the control group, signiifcant difference (P< 0.05). SOD in the observation group were higher than the control group, MDA was signiifcantly lower than that of the control group (P < 0.05).Conclusion Biifdobacterium triple viable combined Mesalamine on treating ulcerative colitis can significantly improve the curative effect, improve the level

  8. 美沙拉嗪联合益生菌对炎症性肠病大鼠模型血清IL-6、TNF-α和IFN-γ含量的影响%The Effect of Combined Treatment of Mesalamine and Probiotics on IL-6,TNF-αand IFN-γof the Rats with Inflammatory Bowel Disease

    Institute of Scientific and Technical Information of China (English)

    晏廷亮; 张帆; 崔道林; 方杰; 龚蕾

    2014-01-01

    To observe the effect of combined treatment of Mesalamine and Probiotics in IL-6, TNF-α and IFN-γ of the rats with Inflammatory bowel disease,and to explore the mechanism of the treatment for inflammatory bowel disease.Method:40 male SD rats were randomly divided into four groups,namely normal control group,model group,Mesalamine group and the combined group.IL-6,TNF-αand IFN-γin the serum of rats were detected by ELISA method.Result:The expression of IL-6,TNF-αand IFN-γin the combined group were significantly lower than those in the model group(P<0.05).Conclusion:The combined treatment of Mesalamine and Probiotics plays an important role in alleviating intestinal inflamm.%目的:观察美沙拉嗪联合益生菌对炎症性肠病大鼠血清中L-6、TNF-α和IFN-γ含量的影响,并初步探讨该方法治疗炎症性肠病的作用机制。方法:将40只雄性SD大鼠随机分为四组,即正常对照组、模型组、美沙拉嗪组和美沙拉嗪益生菌联合组,最后各组大鼠取血,应用ELISA法检测血清中IL-6、TNF-α和IFN-γ含量。结果:美沙拉嗪联合益生菌组IL-6、TNF-α和IFN-γ含量的表达均明显低于模型组(P<0.05)。结论:美沙拉嗪联合益生菌在缓解肠道炎症中发挥着重要作用。

  9. Clinical Effects of Probiotics and Mesalamine in the Treatment of Patients With Inflammatory Bowel Disease%益生菌与美沙拉嗪用于炎症性肠病患者治疗中的临床效果观察

    Institute of Scientific and Technical Information of China (English)

    王进国

    2016-01-01

    Objective To explore the clinical curative effect of Probiotics and Mesalamine in the treatment of patients with inflammatory bowel disease.Methods From January 2014 to March 2016, chose 120 cases of patients with inflammatory bowel disease in in our hospital, the clinical data were retrospectively analyzed.Results The efficiency of B group was 96.67%, A group was 81.03%, the difference was statisticaly significant(P<0.05),adverse reaction rate of B group was 1.67%, A group was 13.33%, the difference was statisticaly significant(P<0.05).Conclusion The combination of probiotics and Mesalamine in patients with inflammatory bowel is effective, safe and reliable.%目的:探讨炎症性肠病患者经益生菌与美沙拉嗪治疗的临床疗效。方法选取2014年1月~2016年3月我院收治的120例炎症性肠病患者的临床资料进行研究,回顾性分析患者的临床资料。结果 B组有效率为96.67%,A组为81.03%,差异有统计学意义(P<0.05);B组不良反应率为1.67%,A组为13.33%,差异有统计学意义(P<0.05)。结论炎症性肠患者者采用美沙拉嗪联合益生菌治疗,效果显著,安全可靠。

  10. Adding once-daily lixisenatide for type 2 diabetes inadequately controlled by established basal insulin: a 24-week, randomized, placebo-controlled comparison (GetGoal-L)

    National Research Council Canada - National Science Library

    Riddle, Matthew C; Aronson, Ronnie; Home, Philip; Marre, Michel; Niemoeller, Elisabeth; Miossec, Patrick; Ping, Lin; Ye, Jenny; Rosenstock, Julio

    2013-01-01

    ...). We conducted a double-blind, parallel-group, placebo-controlled trial. Patients (n = 495) with established basal insulin therapy but inadequate glycemic control were randomized to add lixisenatide 20...

  11. Long term effectiveness of once-daily unboosted atazanavir plus abacavir/lamivudine as a switch strategy in subjects with virological suppression

    DEFF Research Database (Denmark)

    Llibre, Josep M; Cozzi-Lepri, Alessandro; La Rosa, Jorge Antonio Valencia;

    2014-01-01

    routine however are scant. METHODS: We evaluated treatment outcomes of ATV400+ABC/3TC in pre-treated subjects in the EuroSIDA cohort with undetectable HIV-1 RNA, and previous ABC experience or assumed previous HLA B57*01 testing. We performed a time to loss of virologic response (TLOVR below 50 c....../mL) and a snapshot analysis at 48, 96 and 144 weeks. Virological failure (VF) was defined as a confirmed plasma HIV-1 RNA >50 c/mL. RESULTS: We included 258 subjects: 176 (68%) male, median age 46 (IQR 41, 53) y, 225 (87.2%) white, hepatitis virus co-infection 36%, median baseline CD4 at switch 540 cells (360, 700......, respectively, 89.5 [95% CI 85.1, 92.9]/88 [83.4, 91.7]/86.3% [81.6, 90.4] (TLOVR, composite endpoint failure or stop for any reason) and the risk of VF was 8.3/7.6/7.6%. In the snapshot analysis HIV-RNA was below 50 c/mL in 72.5/65.9/51.6%, respectively, and >50 c/mL in 6.6/5.4/4.3%. Only 0...

  12. Investigation of the pharmacokinetic interactions of deferasirox, a once-daily oral iron chelator, with midazolam, rifampin, and repaglinide in healthy volunteers.

    Science.gov (United States)

    Skerjanec, Andrej; Wang, Jixian; Maren, Kelly; Rojkjaer, Lisa

    2010-02-01

    Deferasirox, a newly developed iron chelator, was coadministered orally with either a known inducer of drug metabolism or with cosubstrates for cytochrome P450 (CYP) to characterize the potential for drug-drug interactions. In the induction assessment, single-dose deferasirox pharmacokinetics were obtained in the presence and absence of a repeated-dose regimen of rifampin. In the CYP3A interaction evaluation, midazolam and its active hydroxylated metabolite were assessed after single doses of midazolam in the presence and absence of steady-state concentrations of deferasirox. To test for interaction at the level of CPY2C8, single-dose repaglinide pharmacokinetics/pharmacodynamics were determined with and without repeated-dose administration of deferasirox. After rifampin, a significant reduction (44%) in plasma exposure (AUC) to deferasirox was observed. Upon coadministration of midazolam, there was a modest reduction of up to 22% in midazolam exposure (AUC, C(max)), suggesting a modest induction of CYP3A4/5 by deferasirox. Def erasirox caused increases in repaglinide plasma C(max) and AUC of 1.5-fold to over 2-fold, respectively, with little change in blood glucose measures. Specific patient prescribing recommendations were established when coadministering deferasirox with midazolam, repaglinide, and rifampin. These recommendations may also apply to other substrates of CYP3A4/5 and CYP2C8 or potent inducers of glucuronidation.

  13. Genistein administered as a once-daily oral supplement had no beneficial effect on the tibia in rat models for postmenopausal bone loss.

    Science.gov (United States)

    Turner, Russell T; Iwaniec, Urszula T; Andrade, Juan E; Branscum, Adam J; Neese, Steven L; Olson, Dawn A; Wagner, Lindsay; Wang, Victor C; Schantz, Susan L; Helferich, William G

    2013-06-01

    Estrogen deficiency after menopause results in rapid bone loss, predisposing women to osteoporotic fractures. Genistein, a phytoestrogen present in high concentrations in soy, is an ingredient in dietary supplements aggressively marketed for bone health. However, in a recent long-duration clinical trial in postmenopausal women, the efficacy of soy extracts in reducing bone loss was disappointing. To better understand the failure of soy extracts to consistently induce a robust skeletal response in women, we investigated the long-term (5 mo) efficacy of genistein, administered as a daily oral supplement, (1) in preventing cancellous bone loss in skeletally mature virgin Long-Evans rats ovariectomized at 7 months of age and (2) in improving cancellous bone mass and architecture in aged retired-breeder rats ovariectomized at 16 or 22 months of age. Rats within each age group were randomly assigned into one of three treatment groups (n = 7-12 rats/group): (1) vehicle control, (2) genistein 485 μg/day, or (3) genistein 970 μg/day, resulting in mean (SE) serum genistein levels of 0.18 (0.10), 0.76 (0.15), and 1.48 (0.31) μM, respectively. Total tibia bone mass and density were evaluated using dual-energy x-ray absorptiometry, whereas cancellous bone mass and architecture in the tibial metaphysis, as well as cortical bone mass and architecture in the tibial diaphysis, were evaluated by micro-CT. Oral genistein administered as a dietary supplement did not influence the cumulative effects of ovariectomy, aging, and/or reproductive history on cancellous and cortical bone mass and architecture. Serum levels of genistein similar to those in women consuming a high-soy diet are ineffective in preventing or treating bone loss in rat models for postmenopausal osteoporosis.

  14. Comparison of the efficacy and safety of once-daily dosing and on-demand use of udenafil for type 2 diabetic patients with erectile dysfunction

    Institute of Scientific and Technical Information of China (English)

    Soon Hyun Park; Sung Woo Park; Bong Yun Cha; Ie Byung Park; Kyung Wan Min; Yeon Ah Sung; Tae Hwa Kim; Jae Min Lee; Kang Seo Park

    2015-01-01

    We compared the efficacy and safety between once‑daily dosing and on‑demand use of udenafil for type 2 diabetic patients with erectile dysfunction (ED). A multi‑center, randomized, open‑label, parallel‑group, 12‑week study was conducted. 161 patients who improved with on‑demand 200 mg of udenafil according to Sexual Encounter Profile (SEP) diary Question 2 and 3 (Q2 and Q3) were randomized into 200 mg on‑demand (n = 80) or 50 mg once‑daily (n = 81) dosing groups for 8 weeks. The dosing period was followed by a 4‑week treatment‑free period. The primary efficacy endpoint was the change of the International Index of Erectile Function (IIEF) erectile function domain (EFD) score. The secondary efficacy endpoints included changes to the SEP diary Q2, Q3, IIEF Q3, Q4, other domains of IIEF, Global Assessment Question, and shift to the normal rate (EFD ≥ 26). Vascular endothelial markers were also assessed. The IIEF‑EFD score of both groups improved after 8 weeks of treatment (P < 0.0001). There was no statistically significant difference between two groups. Improvement was not maintained after the treatment‑free follow‑up period. Similar results were observed in the secondary efficacy endpoints. There was also no significant difference in vascular endothelial markers. Daily udenafil was well‑tolerated, and there was no significant difference in the adverse drug reactions and adverse events between the two groups. Flushing and headache were the most frequent adverse events. Both regimens improved ED in diabetic patients and were well‑tolerated. Further studies are needed to assess the effect of daily udenafil treatment in diabetic patients.

  15. Comparison of vildagliptin twice daily vs. sitagliptin once daily using continuous glucose monitoring (CGM: Crossover pilot study (J-VICTORIA study

    Directory of Open Access Journals (Sweden)

    Sakamoto Masaya

    2012-08-01

    Full Text Available Abstract Background No previous studies have compared the DPP-4 inhibitors vildagliptin and sitagliptin in terms of blood glucose levels using continuous glucose monitoring (CGM and cardiovascular parameters. Methods Twenty patients with type 2 diabetes mellitus were randomly allocated to groups who received vildagliptin then sitagliptin, or vice versa. Patients were hospitalized at 1 month after starting each drug, and CGM was used to determine: 1 mean (± standard deviation 24-hour blood glucose level, 2 mean amplitude of glycemic excursions (MAGE, 3 fasting blood glucose level, 4 highest postprandial blood glucose level and time, 5 increase in blood glucose level after each meal, 6 area under the curve (AUC for blood glucose level ≥180 mg/dL within 3 hours after each meal, and 7 area over the curve (AOC for daily blood glucose level Results The mean 24-hour blood glucose level was significantly lower in patients taking vildagliptin than sitagliptin (142.1 ± 35.5 vs. 153.2 ± 37.0 mg/dL; p = 0.012. In patients taking vildagliptin, MAGE was significantly lower (110.5 ± 33.5 vs. 129.4 ± 45.1 mg/dL; p = 0.040, the highest blood glucose level after supper was significantly lower (206.1 ± 40.2 vs. 223.2 ± 43.5 mg/dL; p = 0.015, the AUC (≥180 mg/dL within 3 h was significantly lower after breakfast (484.3 vs. 897.9 mg/min/dL; p = 0.025, and urinary CPR level was significantly higher (97.0 ± 41.6 vs. 85.2 ± 39.9 μg/day; p = 0.008 than in patients taking sitagliptin. There were no significant differences in plasma HbA1c, GA, 1,5AG, IRI, CPR, BNP, or PAI-1 levels between patients taking vildagliptin and sitagliptin. Conclusions CGM showed that mean 24-h blood glucose, MAGE, highest blood glucose level after supper, and hyperglycemia after breakfast were significantly lower in patients with type 2 diabetes mellitus taking vildagliptin than those taking sitagliptin. There were no significant differences in BNP and PAI-1 levels between patients taking vildagliptin and sitagliptin. Trial registration UMIN000007687

  16. Switching from NPH insulin to once-daily insulin detemir in basal-bolus-treated patients with diabetes mellitus: data from the European cohort of the PREDICTIVE study.

    LENUS (Irish Health Repository)

    Sreenan, S

    2008-12-01

    The PREDICTIVE study is a multinational observational study designed to follow up patients with diabetes who started insulin detemir (IDet) in routine care. Recruitment started in June 2004 and is ongoing in some countries.

  17. Long term effectiveness of once-daily unboosted atazanavir plus abacavir/lamivudine as a switch strategy in subjects with virological suppression

    Directory of Open Access Journals (Sweden)

    Josep M Llibre

    2014-11-01

    (3. Effectiveness data of ATV400+ABC/3TC as a switch strategy in clinical routine however are scant. Methods: We evaluated treatment outcomes of ATV400+ABC/3TC in pre-treated subjects in the EuroSIDA cohort with undetectable HIV-1 RNA, and previous ABC experience or assumed previous HLA B57*01 testing. We performed a time to loss of virologic response (TLOVR below 50 c/mL and a snapshot analysis at 48, 96 and 144 weeks. Virological failure (VF was defined as a confirmed plasma HIV-1 RNA >50 c/mL. Results: We included 258 subjects: 176 (68% male, median age 46 (IQR 41, 53 y, 225 (87.2% white, hepatitis virus co-infection 36%, median baseline CD4 at switch 540 cells (360, 700, time with VL≤ 50 c/mL 45 (24, 69 months. The median calendar year of switching was 2008 (2006, 2010. The 3rd drug in previous regimen was ATV/r in 70 (27.1%, other PI/r in 25 (9.7%, and other 163 (63.2%; 85 (32.9% had previously failed with a PI. The virological response at 48/96/144 weeks was, respectively, 89.5 [95% CI 85.1, 92.9]/88 [83.4, 91.7]/86.3% [81.6, 90.4] (TLOVR, composite endpoint failure or stop for any reason and the risk of VF was 8.3/7.6/7.6%. In the snapshot analysis HIV-RNA was below 50 c/mL in 72.5/65.9/51.6%, respectively, and >50 c/mL in 6.6/5.4/4.3%. Only 0.8/1.9/3.5% discontinued due to adverse events. There was a high rate of discontinuations due to other reasons or with VL missing in window. In a multivariate adjusted analysis, we observed an association between VF and nadir CD4 count (RH 0.60 [0.39, 0.93] per 100 cells higher, time with VL≤50 c/mL (RH 0.89 [0.81, 0.98] per 6 months longer and previous failure with a PI (3.04 [1.36, 6.80]. There was no association with gender, age, hepatitis virus co-infection, CD4 count at time of switching or third drug used in the previous regimen. Conclusions: A switch to ATV400+ABC/3TC in selected subjects with HIV-RNA below 50 c/mL is associated with relatively low rates of VF and discontinuation due to adverse events. Use might be considered in those with long-term suppression and without prior PI failure. Larger cohorts are required to further define the appropriate selection criteria.

  18. Improvement of executive functions in boys with attention deficit hyperactivity disorder: an open-label follow-up study with once-daily atomoxetine.

    Science.gov (United States)

    Gau, Susan Shur-Fen; Shang, Chi-Yung

    2010-03-01

    Atomoxetine is efficacious in reducing symptoms of attention deficit hyperactivity disorder (ADHD) but its effect on executive functions needs more investigation. We examined the effect of atomoxetine on a wide range of non-verbal executive functions among 30 drug-naive male patients with DSM-IV ADHD, aged 8-16 yr, in an open-label 12-wk atomoxetine treatment trial. Before administration of atomoxetine, the participants were assessed by psychiatric interviews, the WISC-III, and the tasks involving executive functions of the Cambridge Neuropsychological Test Automated Battery (CANTAB): Intra-dimensional/Extra-dimensional Shifts (IED), Rapid Visual Information Processing (RVIP), Spatial Span (SSP), Spatial Working Memory (SWM), and Stockings of Cambridge (SOC); and reassessed at weeks 4 and 12. All the raw scores of the CANTAB were transformed to z scores based on a normative sample of 180 children aged 8-16 yr. Results showed significant improvement in executive functions after treatment with atomoxetine for 4 wk or 12 wk including improved shifting and flexibility of attention in the IED; improved spatial short-term memory in the SSP; improved sustained attention and increased response inhibition in the RVIP; improved spatial working memory in the SWM; and improved spatial planning and problem solving in the SOC. Our findings suggested that atomoxetine was associated with significant improvement in various non-verbal executive functions among boys with ADHD, in addition to its well-known efficacy in ADHD-related symptom reductions. However, owing to lack of a placebo-controlled trial design, the findings should be interpreted with caution that changes in performance may be due to practice effects.

  19. Efficacy and safety of once-daily glycopyrronium in predominantly Chinese patients with moderate-to-severe chronic obstructive pulmonary disease: the GLOW7 study [Corrigendum

    Directory of Open Access Journals (Sweden)

    Wang C

    2015-07-01

    Full Text Available Wang C, Sun T, Huang Y, et al. Int J Chron Obstruct Pulmon Dis. 2015;10:57–68.The phone number for the corresponding author Chen Wang should be +86 10 8420 6166.Read the original article

  20. Safety and efficacy of once-daily single generic fixed-drug combination tablet of tenofovir, lamivudine and efavirenz among HIV-infected Thais

    Directory of Open Access Journals (Sweden)

    W Maek-a-Nantawat

    2012-11-01

    Full Text Available Background: Generic fixed dose combinations (FDCs of nucleoside reverse transcriptase inhibitors (NRTIs and non-nucleoside reverse transcriptase inhibitors (NNRTIs is commonly used in resource-limited settings to increase adherence to lifelong treatment. However, the cumulative evidence of the long-term complications, particularly mitochondrial toxicity of NRTIs, especially stavudine (or zidovudine, brings about widespread use of tenofovir (TDF. This study was aimed to assess the efficacy and safety of a FDC comprising 300 mg tenofovir (TDF, 300 mg LAM and 600 mg efavirenz (EFV. Methods: A Phase II open-label clinical trial was conducted at HIV-NAT, Thai AIDS Research Center, Thai Red Cross from April 2010 to December 2011. Patients were eligible to enroll if they were either: 1 on TDF, LAM and EFV as separate tablets, for at least 6 months with an undetectable viral load (= switch arm or 2 treatment-naïve. Safety profiles, including liver and renal functions, were assessed at baseline, weeks 4, 12, 24 and 48. In switch group, mid-dose TDF plasma concentrations were measured by HPLC at baseline and week 4 after a switch to single FDC tablet. Results: A total of 100 patients were enrolled (51 naïve. Median age was 34 years and 30% were female. The median baseline CD4 cell count (IQR was 512 (395–620 cells/L and 232 (164–284 cells/L for the switch arm and ARV-naïve group, respectively. The median (IQR log10 HIV-1 RNA for ARV-naïve group was 4.9 (4.2–5.3 copies/mL. By ITT analysis, the proportion of cases with HIV RNA<50 copies/mL was 93% and 92% at week 24 and 48, respectively. Only 1 confirmed virological failure at week 12 with NNRTI-resistant mutations (A98G, K103N, V118I, E138Q, Y181C. The reported 3 SAEs (severe headache, infective endocarditis, cervical dysplasia were found and one was possibly related to the study drug. There were 49 mild to moderate efavirenz-related central nervous system events, occurring in first few days-weeks. There were no statistically significant changes on renal function and liver enzymes. Mean plasma concentrations of all three drugs in FDC met the acceptable target levels. Conclusion: The generic FDC of TDF/3TC/EFV was well tolerated and efficacious. Our findings lend support to the use of this generic FDC as first-line antiretroviral therapy in resource limited settings.

  1. Long term effectiveness of once-daily unboosted atazanavir plus abacavir/lamivudine as a switch strategy in subjects with virological suppression.

    Science.gov (United States)

    Llibre, Josep M; Cozzi-Lepri, Alessandro; La Rosa, Jorge Antonio Valencia; Pedersen, Court; Ristola, Matti; Losso, Marcelo; Mocroft, Amanda; Mitsura, Victor M; Ormaasen, Vidar; Maltez, Fernando; Beniowski, Marek; Paredes, Roger

    2014-01-01

    Use of unboosted atazanavir (ATV400) is approved in the US but not in Europe (1). Due to pharmacokinetic interactions it should not be used with tenofovir but can be used with abacavir/lamivudine (ABC/3TC) (1, 2) (3). Effectiveness data of ATV400+ABC/3TC as a switch strategy in clinical routine however are scant. We evaluated treatment outcomes of ATV400+ABC/3TC in pre-treated subjects in the EuroSIDA cohort with undetectable HIV-1 RNA, and previous ABC experience or assumed previous HLA B57*01 testing. We performed a time to loss of virologic response (TLOVR below 50 c/mL) and a snapshot analysis at 48, 96 and 144 weeks. Virological failure (VF) was defined as a confirmed plasma HIV-1 RNA >50 c/mL. We included 258 subjects: 176 (68%) male, median age 46 (IQR 41, 53) y, 225 (87.2%) white, hepatitis virus co-infection 36%, median baseline CD4 at switch 540 cells (360, 700), time with VL≤ 50 c/mL 45 (24, 69) months. The median calendar year of switching was 2008 (2006, 2010). The 3rd drug in previous regimen was ATV/r in 70 (27.1%), other PI/r in 25 (9.7%), and other 163 (63.2%); 85 (32.9%) had previously failed with a PI. The virological response at 48/96/144 weeks was, respectively, 89.5 [95% CI 85.1, 92.9]/88 [83.4, 91.7]/86.3% [81.6, 90.4] (TLOVR, composite endpoint failure or stop for any reason) and the risk of VF was 8.3/7.6/7.6%. In the snapshot analysis HIV-RNA was below 50 c/mL in 72.5/65.9/51.6%, respectively, and >50 c/mL in 6.6/5.4/4.3%. Only 0.8/1.9/3.5% discontinued due to adverse events. There was a high rate of discontinuations due to other reasons or with VL missing in window. In a multivariate adjusted analysis, we observed an association between VF and nadir CD4 count (RH 0.60 [0.39, 0.93] per 100 cells higher), time with VL≤50 c/mL (RH 0.89 [0.81, 0.98] per 6 months longer) and previous failure with a PI (3.04 [1.36, 6.80]). There was no association with gender, age, hepatitis virus co-infection, CD4 count at time of switching or third drug used in the previous regimen. A switch to ATV400+ABC/3TC in selected subjects with HIV-RNA below 50 c/mL is associated with relatively low rates of VF and discontinuation due to adverse events. Use might be considered in those with long-term suppression and without prior PI failure. Larger cohorts are required to further define the appropriate selection criteria.

  2. Safety and tolerability of once-daily tiotropium Respimat(®) as add-on to at least inhaled corticosteroids in adult patients with symptomatic asthma

    DEFF Research Database (Denmark)

    Dahl, Ronald; Engel, Michael; Dusser, Daniel

    2016-01-01

    of tiotropium delivered via the Respimat(®) device, compared with placebo, each as add-on to at least ICS therapy, in a pooled sample of adults with symptomatic asthma at different treatment steps. METHODS: Data were pooled from seven Phase II and III, randomised, double-blind, parallel-group trials of 12...... medication. RESULTS: Of 3474 patients analysed, 2157 received tiotropium. The percentage of patients with AEs was comparable between treatment groups: tiotropium 5 μg, 60.8%; placebo 5 μg pool, 62.5%; tiotropium 2.5 μg, 57.1%; placebo 2.5 μg pool, 55.1%. Consistent with the disease profile, the most frequent...... AEs overall were asthma, decreased peak expiratory flow rate (both less frequent with tiotropium) and nasopharyngitis. Overall incidence of dry mouth, commonly associated with use of anticholinergics, was low: tiotropium 5 μg, 1.0%; placebo 5 μg pool, 0.5%; tiotropium 2.5 μg, 0.4%; placebo 2.5 μg pool...

  3. Once-Daily Bedtime Dose of Roxatidine and Ranitidine in Acute Duodenal Ulcer: A Combined Assessment of Acid Inhibitory Activity and Healing Rate.

    Science.gov (United States)

    Savarino, Vincenzo; Mela, Giuseppe Sandro; Zentilin, Patrizia; Mele, Maria Raffaella; Vigneri, Sergio; Termini, Rosanna; Di Mario, Francesco; Ferrana, Marina; Malesci, Alberto; Belicchi, Monica

    1995-12-01

    This study was carried out in order to compare the antisecretory effect of a single bedtime dose of roxatidine 150 mg and ranitidine 300 mg and to assess the relationship between the degree and the duration of acid suppression and the healing rates obtained in duodenal ulcer patients treated with the above regimens. Sixty-three patients with endoscopically proven ulcer underwent 24-h gastric pH-metry on day 0, day 1, and day 28 of treatment with both roxatidine and ranitidine. Ulcer healing was checked endoscopically after 4 weeks of therapy. RESULTS: Eight patients did not complete the study, leaving 55 patients eligible for final analysis, 28 in the roxatidine group and 27 in the ranitidine group. Duodenal ulcers were healed in 24--28 (85%) patients of the former and in 22--27 (81%) patients of the latter group (p minus sign NS). Gastric pH was significantly higher (p roxatidine and ranitidine. There was also do difference between the two active treatments. The pattern of gastric acidity significantly differed (p roxatidine 150 mg and ranitidine 300 mg was able to heal more than 80% of duodenal ulcers within 4 weeks of treatment. The lack of tolerance to H2-blockers in duodenal ulcer patients contributes to this good result. The antisecretory effect of H2-antagonists is reduced in nonresponder patients with respect to responder patients and this is mainly due to an impaired control of nocturnal acidity.

  4. Once-daily intravenous busulfan with therapeutic drug monitoring compared to conventional oral busulfan improves survival and engraftment in children undergoing allogeneic stem cell transplantation

    NARCIS (Netherlands)

    Bartelink, Imke H.; Bredius, Robbert G. M.; Ververs, Tessa T.; Raphael, Martine F.; van Kesteren, Charlotte; Bierings, Marc; Rademaker, Carin M. A.; den Hartigh, J.; Uiterwaal, Cuno S. P. M.; Zwaveling, Juliette; Boelens, Jaap J.

    2008-01-01

    Because of intra- and interindividual variability, bioavailability, and pharmacokinetics of busulfan (Bu) in children, oral busulfan without therapeutic drug monitoring (TDM) is assumed to be associated with higher graft failure rates as well as higher toxicity (eg, veno-occlusive disease [VOD]). Th

  5. [Bacteriological monitoring of the treatment of Pseudomonas aeruginosa infections with amikacin administrated at once-daily dosis in patients with cystic fibrosis].

    Science.gov (United States)

    Canis, F; Husson, M O; Vic, P; Ategbo, S; Turck, D; Courcol, R; Leclerc, H

    1995-04-01

    The interest of the treatment with a single daily dose of amikacin (AMK) in cystic fibrosis (CF) patients with P. aeruginosa infections has been much debated. The aim of work was to study the efficiency of this treatment on (CF) patients with chronic bronchopulmonary P. aeruginosa infections previously treated for two weeks with the combination ceftazidime (CAZ 200 mg/day in 3 inj. IVD) and AMK (35 mg/day in one IV perf. of 30 minutes). The bacteriological supervision of this treatment was performed 1: by the determination of MICs before and after treatment, 2: by the decrease of P. aeruginosa colonization immediately after this treatment and during 11 months, 3: by the identification of P. aeruginosa strains with phenotypic methods (serotyping and antibiotyping) and with genotypic method (pulsed field gel electrophoresis). The use of AMK in a single daily dose in order to treat chronic lung infections colonized with P. aeruginosa susceptible to this antibiotic shows encouraging results as far as bacteriology is concerned: this treatment has given means to reduce colonization for a month in 15 of 18 patients. For 9 of the 18 patients, no P. aeruginosa strains were isolated for nine months. The serotyping and antibiotyping systems do not enable us to study the P. aeruginosa epidemiology. Genome macrorestriction fingerprinting of P. aeruginosa in pulsed field gel electrophoresis confirms that patient with CF were colonized with one or several clones. In our study no variation of these clones was noticed for the first eleven months. Genome macrorestriction fingerprinting appears to be one of the most effective methods for delineate strains of P. aeruginosa colonizing CF patients.

  6. Effectiveness of Antiretroviral Therapy in Individuals Who for Economic Reasons Were Switched From a Once-Daily Single-Tablet Regimen to a Triple-Tablet Regimen

    DEFF Research Database (Denmark)

    Engsig, Frederik N; Gerstoft, Jan; Helleberg, Marie

    2014-01-01

    1, 2011 to obtain economic savings. METHODS AND FINDINGS: From the Capital Region of Denmark (covering two-thirds of the Danish HIV patients), we included combination antiretroviral therapy (cART)-naive patients who administered STR-TEE from April 1, 2010 to March 31, 2011 (n = 111) or TTR-TEL from......BACKGROUND: To assess the impact on virological outcomes of a switch from branded single-tablet regimen (STR) including tenofovir, efavirenz, and emtricitabine (STR-TEE) to generic triple-tablet regimen (TTR), including tenofovir, efavirenz, and lamivudine (TTR-TEL), which was implemented on April...

  7. The Evaluation of Mesalamine Oral Combined with Suppository in Treat-ment of Left-sided Ulcerative Colitis Effect%美沙拉嗪口服联合栓剂治疗左半溃疡性结肠炎的效果评价

    Institute of Scientific and Technical Information of China (English)

    王连忠

    2016-01-01

    Objective Research on the evaluation of Mesalamine oral combined with suppository in treatment of left-sided ulcerative colitis effect. Methods A total of 628 cases of left-sided ulcerative colitis were selected from January 2013 to December 2015 in the hospital.Randomly divided into observation group 300 cases, 328 cases in the control group,both of them was given the Mesalamine Slow Release Tablets .Based on the observation group , the control group was given the Mesalamine suppository.The total effective rate and adverse reaction rate of the two groups were com-pared. Results The efficiency of the observation group 86.00% was higher than that of the control group 64.63%, the difference was statistically significant(P﹤0.05);There was no significant difference in the incidence of adverse reactions between the observation group 6.67% and the control group 6.40%(P>0.05). Conclusion Compared to mesalazine oral combined with suppository in the treatment of eft-sided ulcerative colitis with simple mesalazine oral treatment can in-crease the drug concentration at the local intestinal and improve the curative effect, adverse reaction rate did not in-crease, it is worth in clinical promotion.%目的:探究美沙拉嗪口服联合栓剂治疗左半溃疡性结肠炎的效果评价。方法选取该院2013年1月—2015年12月共收治628例左半溃疡性结肠炎,随机分为观察组300例,对照组328例,均给予美沙拉嗪肠溶片,观察组在对照组的基础之上给予美沙拉嗪栓剂,比较两组的总有效率及不良反应发生率。结果观察组使用美沙拉嗪口服联合栓剂治疗的有效率为86.00%明显高于对照组的64.63%,差异有统计学意义(P﹤0.05);观察组不良反应发生率6.67%与对照组6.40%比较差异无统计学意义(P>0.05)。结论美沙拉嗪口服联合栓剂治疗左半溃疡性结肠炎与单纯美沙拉嗪口服治疗相比,可以增加肠道局部的药物浓度,提高疗效,不良

  8. Combined with Traditional Chinese Medicine Formulations of Mesalamine Retention Enema Treatment of Chronic Recurrent Type Clinical Analysis of Ulcerative Colitis%美沙拉嗪联合中药制剂保留灌肠治疗慢性反复发作型溃疡性结肠炎的临床疗效分析

    Institute of Scientific and Technical Information of China (English)

    雷波; 伍平; 汪功华

    2012-01-01

      目的探讨美沙拉嗪联合中药制剂保留灌肠治疗慢性反复发作型溃疡性结肠炎的临床疗效.方法回顾性分析2005年7月~2012年7月在安徽省安庆市第一人民医院消化内科收治的59例慢性反复发作型溃疡性结肠炎的临床资料.将59例慢性反复发作型溃疡性结肠炎患者随机分为试验组和对照组,试验组31例,对照组28例.试验组予以美沙拉嗪(0.5g,4次/ d)联合中药制剂保留灌肠;对照组予以美沙拉嗪(0.5g,4次/ d)各治疗8周后观察其临床疗效.结果试验组31例患者治愈15例、显效12例、有效1例、无效3例,总有效率90.32%,对照组28例病人治愈11例、显效13例、有效0例、无效4例,总有效率85.71%.两组比较有统计学差异(P <005).结论美沙拉嗪联合中药制剂保留灌肠治疗慢性反复发作型溃疡性结肠炎具有疗效确切、治愈率高、不良反应少,且价格低廉.%  Objective To explore the the mesalazine joint Chinese medicine preparations retention enema clinical efficacy for the treatment of chronic ulcerative colitis relapse type. Method Retrospective analysis of clinical data from July 2005 to July 2012 in the Department of Gastroenterology, the First People's Hospital of Anqing City, Anhui Province admitted 59 patients with chronic recurrent type of ulcerative colitis. Repeated attack of the 59 patients with chronic ulcerative colitis patients were randomly divided into experimental and control groups, the test group (31 cases), 28 cases of the control group. Test group was treated with mesalamine (0.5g, 4 times / d) combined with traditional Chinese medicine preparations retention enema; clinical efficacy in the control group were given mesalamine (0.5g, 4 times / d) after eight weeks of each treatment.Result Test group of 31 patients, 15 cases were cured, 12 cases markedly effective one cases, 3 cases, the total effective rate was 90.32% in the control group of 28 patients, 11 cases were

  9. Validation of HPLC, DPPH• and nitrosation methods for mesalamine determination in pharmaceutical dosage forms Validação dos métodos de CLAE, DPPH• e nitrosação para determinação de mesalazina em formas farmacêuticas

    Directory of Open Access Journals (Sweden)

    Janice Aparecida Rafael

    2007-03-01

    Full Text Available Mesalamine (5-aminosalicylic acid, 5-ASA is used because of its local effects in the treatment of inflammatory bowel disease. Therefore, the aims of this work were to compare and validate three analytical methods for the quality control of commercial coated tablets containing 5-ASA: high performance liquid chromatography (HPLC, 1,1-diphenyl-2-picrylhydrazyl radicals (DPPH• and nitrosation. The parameters linearity, precision and accuracy were studied in this work. HPLC with ultraviolet detection at 254 nm was carried out with a C18 column and a mobile phase constituted of 30 mmol/L monobasic phosphate buffer (pH 7.0 and methanol (70:30; v/v, with 25% tetrabutylammonium hydrogen sulphate. The DPPH• method was performed at 517 nm and using 100 mmol/L acetate buffer, pH 5.5, ethanol and 250 µmol/L ethanolic solution of DPPH•. The nitrosation method was accomplished by using a platinum electrode and standard 0.1 mol/L sodium nitrite as titrant solution. Repeatability (intra-day and intermediate precision (inter-day, expressed as RSD, were lower than 3%. The experimental recoveries were between 72.5 and 99.9%. Statistical analysis by one-way ANOVA, followed by the multiple comparison test of Bonferroni showed no significant difference among the three methods. All proposed methods can be used for the reliable quantitation of 5-ASA in pharmaceutical dosage forms.Mesalazina (ácido 5-aminosalicílico, 5-ASA é utilizado devido seu efeito local no tratamento de doença inflamatória intestinal. Assim, o objetivo deste trabalho foi comparar e validar três métodos analíticos para o controle de qualidade de comprimidos comerciais revestidos contendo 5-ASA: cromatografia líquida de alta eficiência (CLAE, radical 1,1-difenil-2-picril-hidrazil (DPPH• e nitrosação. Os parâmetros linearidade, precisão e exatidão foram estudados neste trabalho. CLAE com detecção ultravioleta em 254 nm foi realizada utilizando coluna C18 e a eluição em fase m

  10. Long-Term Outcomes after Treatment with Clofarabine ± Fludarabine with Once-Daily Intravenous Busulfan as Pretransplant Conditioning Therapy for Advanced Myeloid Leukemia and Myelodysplastic Syndrome.

    Science.gov (United States)

    Alatrash, Gheath; Thall, Peter F; Valdez, Benigno C; Fox, Patricia S; Ning, Jing; Garber, Haven R; Janbey, Selma; Worth, Laura L; Popat, Uday; Hosing, Chitra; Alousi, Amin M; Kebriaei, Partow; Shpall, Elizabeth J; Jones, Roy B; de Lima, Marcos; Rondon, Gabriela; Chen, Julianne; Champlin, Richard E; Andersson, Borje S

    2016-10-01

    Pretransplant conditioning regimens critically determine outcomes in the setting of allogeneic stem cell transplantation (allo-SCT). The use of nucleoside analogs such as fludarabine (Flu) in combination with i.v. busulfan (Bu) has been shown to be highly effective as a pretransplant conditioning regimen in acute myeloid leukemia (AML), chronic myeloid leukemia (CML), and myelodysplastic syndrome (MDS). Because leukemia relapse remains the leading cause of death after allo-SCT, we studied whether clofarabine (Clo), a nucleoside analog with potent antileukemia activity, can be used to complement Flu. In a preliminary report, we previously showed the safety and efficacy of Clo ± Flu with i.v. Bu in 51 patients with high-risk AML, CML, and MDS. The study has now been completed, and we present long-term follow-up data on the entire 70-patient population, which included 49 (70%), 8 (11%), and 13 (19%) patients with AML, MDS, and CML, respectively. Thirteen patients (19%) were in complete remission, and 41 patients (59%) received matched unrelated donor grafts. Engraftment was achieved in all patients. Sixty-three patients (90%) achieved complete remission. There were no deaths reported at day +30, and the 100-day nonrelapse mortality rate was 4% (n = 3). Thirty-one percent of patients (n = 22) developed grades II to IV acute graft-versus-host disease, and the median overall survival and progression-free survival times were 2.4 years and .9 years, respectively. Our results confirm the safety and overall and progression-free survival advantage of the arms with higher Clo doses and lower Flu doses, which was most prominent in the AML/MDS group.

  11. Pharmacokinetic and Pharmacodynamic Comparison of Once-Daily Efavirenz (400 mg vs. 600 mg) in Treatment-Naïve HIV-Infected Patients: Results of the ENCORE1 Study.

    Science.gov (United States)

    Dickinson, L; Amin, J; Else, L; Boffito, M; Egan, D; Owen, A; Khoo, S; Back, D; Orrell, C; Clarke, A; Losso, M; Phanuphak, P; Carey, D; Cooper, D A; Emery, S; Puls, R

    2015-10-01

    Daily efavirenz 400 mg (EFV400) was virologically noninferior to 600 mg (EFV600) at 48 weeks in treatment-naïve patients. We evaluated EFV400 and EFV600 pharmacokinetics (NONMEM v. 7.2), assessing patient demographics and genetic polymorphisms (CYP2B6, CYP2A6, CYP3A4, NR1I3) as covariates and explored relationships with efficacy (plasma HIV-RNA (pVL) T/983T>C/CYP2A6*9B/*17 and weight were associated with efavirenz CL/F. Exposure was significantly lower for EFV400 (geometric mean ratio, GMR; 90% confidence interval, CI: 0.73 (0.68-0.78)) but 97% (EFV400) and 98% (EFV600) of evaluable pVL was HIV suppression was comparable between doses despite significantly lower EFV400 exposure. Comprehensive evaluation of efavirenz pharmacokinetics/pharmacodynamics revealed important limitations in the accepted threshold concentration.

  12. Rivaroxaban-once daily, oral, direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation: rationale and design of the ROCKET AF study

    DEFF Research Database (Denmark)

    NN, NN

    2010-01-01

    in advanced development as an alternative to warfarin for the prevention and treatment of thromboembolic disorders. METHODS: ROCKET AF is a randomized, double-blind, double-dummy, event-driven trial, which aims to establish the noninferiority of rivaroxaban compared with warfarin in patients with nonvalvular...... nonmajor bleeding events. Over 14,000 patients have been randomized at 1,100 sites across 45 countries, and will be followed until 405 primary outcome events are observed. CONCLUSION: The ROCKET AF study will determine the efficacy and safety of rivaroxaban as an alternative to warfarin for the prevention...

  13. Medication Persistence, Duration of Treatment, and Treatment-switching Patterns Among Canadian Patients Taking Once-daily Extended-release Methylphenidate Medications for Attention-Deficit/Hyperactivity Disorder: A Population-based Retrospective Cohort Study.

    Science.gov (United States)

    Park-Wyllie, Laura; Van Stralen, Judy; Almagor, Doron; Dobson-Belaire, Wendy; Charland, Katia; Smith, Andrew; Le Lorier, Jacques

    2016-08-01

    We conducted a retrospective cohort study to compare medication use patterns of a long-acting extended-release methylphenidate (Osmotic Release Oral System [OROS(®)] methylphenidate, CONCERTA(®)) and Teva-methylphenidate (methylphenidate ER-C), a generic drug determined by the Canadian regulatory authority, Health Canada, to be bioequivalent to OROS(®) methylphenidate. We established an OROS(®) methylphenidate-experienced and new-user population cohort to compare medication use patterns, including medication persistence, duration of therapy, and treatment-switching patterns. Multivariable log-binomial regression was used to adjust for confounders of the associations with persistence. In the OROS(®) methylphenidate-experienced cohort (n = 21,940), OROS(®) methylphenidate was associated with a 70% higher rate of medication persistence at 12 months relative to methylphenidate ER-C (adjusted relative risk = 1.70; 95% CI, 1.64-1.77). In the new-user cohort (n = 20,410), OROS(®) methylphenidate had a 58% higher rate of medication persistence relative to methylphenidate ER-C (adjusted relative risk = 1.58; 95% CI, 1.51-1.65). Median duration of therapy was significantly longer in patients taking OROS(®) methylphenidate compared with those taking methylphenidate ER-C, and treatment-switching occurred significantly more frequently in patients taking methylphenidate ER-C compared with those taking OROS(®) methylphenidate. Significant differences were observed in how the medications were used by patients in the real-world setting. Because the data sources were administrative databases, it was not possible to control for all potentially important confounding variables. Although differences in medication persistence may not directly reflect differences in treatment efficacy, the findings are important because these products are used interchangeably in a number of Canadian provinces. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

  14. Effectiveness of a nonsteroidal anti-inflammatory drug for nocturia on patients with benign prostatic hyperplasia: a prospective non-randomized study of loxoprofen sodium 60 mg once daily before sleeping.

    Directory of Open Access Journals (Sweden)

    Araki T

    2004-02-01

    Full Text Available We explored the effectiveness of loxoprofen sodium (loxoprofen, which is the most common non-steroidal anti-inflammatory drug (NSAID in Japan, for patients with benign prostatic hyperplasia (BPH complaining of nocturia. A total of 93 BPH patients aged 49-84 years were enrolled in the study. These patients had received standard drug therapy with alpha1-blocker for BPH, followed by anticholinergic drugs, hypnotics, tricyclic antidepressants, and/or antiduretic hormone, but they still complained about 2 or more episodes of nocturia. They each took a single 60-mg tablet of loxoprofen prior to sleeping at night for 14 days in addition to their BPH treatments. The effects were assessed by questionnaire before and after treatment as excellent (nocturia disappeared or decreased by 2 or more voids/night, improved (nocturia decreased by 1 void/night, unchanged, or worsened (nocturia increased. Nocturia improved or disappeared in 74.2% of patients: excellent, improved, unchanged, and worsened results were obtained in 37.6%, 36.6%, 21.5%, and 4.3% of patients, respectively. The effects were better in patients whose baseline nocturia was > 2 times than in those with a lesser frequency at enrollment (P = 0.04. Loxoprofen can be an effective and useful treatment option for patients with BPH complaining of refractory nocturia.

  15. A New, Once-daily, Optimized, Fixed Combination of Clindamycin Phosphate 1.2% and Low-concentration Benzoyl Peroxide 2.5% Gel for the Treatment of Moderate-to-Severe Acne

    OpenAIRE

    Gold, Michael H.

    2009-01-01

    The treatment of acne with combination therapy is commonplace with treatment aimed at sustained efficacy with minimal side effects, maximum adherence, and the avoidance of bacterial resistance. Combinations containing clindamycin and benzoyl peroxide have been shown to be effective, but the irritation caused by the concentration of benzoyl peroxide 5% in the more commonly used, fixed combinations can be limiting. In addition, surfactants, preservatives, and high levels of organic solvents, in...

  16. Evaluation of MMX1902 as an Oral Treatment for Duchenne Muscular Dystrophy

    Science.gov (United States)

    2016-10-01

    type control mice. Further, embryonic myosin heavy chain (eMHC) staining of the diaphragm showed a significant increase in eMHC positive muscle...resulting in cardiac functional measures comparable to exercised wild-type control mice (Table 1). Further, embryonic myosin heavy chain (eMHC) staining of...and delivers supplies from lab/receipt area to procedure room. Michael Weinberg Research Lab Technician 2 ID #2009562 9.0 calendar months

  17. Clinical efficacy of glutamine compound joint mesalamine in treatment of nonspecific small ulcer%复方谷氨酰胺联合美莎拉嗪治疗非特异性小肠溃疡的临床疗效观察

    Institute of Scientific and Technical Information of China (English)

    郑荣娟; 郝丽君; 赵莉; 胡爱萍; 吴贵楷

    2015-01-01

    Objective To investigate the clinical efficacy of glutamine compound joint mesalamine in treatment of nonspecific small ulcer.Methods Selected 72 cases of non specific small ulcer patients, they were randomly divided into two groups with 36 patients in each group, the observation group were used Sarah triazine compound joint US glutamine treatment, the control group received glutamine compound treatment, four weeks as a course of treatment, observation intestinal symptoms in patients before and after treatment, diarrhea, abdominal pain and bloating of patients were recorded, improvement of symp-toms and clinical efficacy were evaluated.Results After four weeks of treatment, observation and control groups’ total effi-ciency were 97.2%and 80.5%respectively, the total efficiency of the observation group was significantly higher than that of control group (χ2 =20.71, P <0.05).After two and four weeks of treatment, diarrhea were reduced in both of the two groups (control group:t =3.95, t =3.76, observation group:t =3.23, t =3.11, P <0.05), observation group was better than control group ( t =2.36, t =2.41, P <0.05) .Abdominal pain, bloating and diarrhea were relieved than before treat-ment in both group (control group:t =6.18, t =4.07, t =4.26, observation group:t =6.31, t =4.52, t =4.76, P <0.05), and observation group was better than that of control group ( t =2.97, t =2.65, t =2.58, P <0.05).Compared with before treatment, serum TNF-α, IL-6, IL-8 levels were decreased in both of the two groups ( observation group:t =4.35, t =4.51, t =4.43, control group:t =4.18, t =4.45, t =4.37, P <0.05), observation group were significantly lower than that of the control group, the difference was statistically significant ( t =2.85, t =2.91, t =3.19, P <0.05). Conclusion Sarah triazine compound glutamine joint US in treatment of nonspecific small ulcer effect has obvious effect, its worthy of clinical application.%目的:观察复方谷氨酰胺联合美莎拉嗪治疗非特

  18. 老年人微观肠炎临床特点和美沙拉嗪短期治疗效果分析%Clinical features of microscopic colitis in the elderly and short-term effect of mesalamine on microscopic colitis

    Institute of Scientific and Technical Information of China (English)

    张俊峰; 刘娜; 魏子白; 王少黎

    2013-01-01

    Objective To investigate clinical features of microscopic colitis (MC) in the elderly and short-term effect of mesalamine on MC.Methods Totally 116 elderly patients with MC in our hospital were recruited from January 2011 to December 2011.Clinical manifestations,use of MC related drugs (MCRDs),pathological classifications and short-term effect of mesalazine were collected and analyzed.Results MC patients accounted for 27.6 % in elderly patients with chronic diarrhea,who presented with mild to middle watery or mucous stool,and only 1.7% of MC patients accompanied with severe stomach pain.Collagenous colitis (CC) and lymphocytic enteritis (LC) accounted for 31.9% and 68.1%,respectively in MC patients and 50% of them had MCRDs taking history.There was a significant difference in short-term effective rate between CC group and LC group at 4 weeks after mesalazine treatment (64.9% vs.84.8%,x2 =5.929,P=0.015).The effective rate was significantly related with the relief of pathology in LC group (x2 =5.896,P=0.015).The relapse rate had no significant difference between CC group and LC group at 8 weeks after withdrawal of mesalazine treatment (45.8% vs.34.3 %,P =0.317).Conclusions MC may be one of the main reasons leading to chronic diarrhea in the elderly.Mesalazine has a better effect for the short-term treatment of MC in the elderly,but the long-term maintenance therapy still needs further study.%目的 研究老年人微观肠炎临床特点及美沙拉嗪短期治疗效果. 方法 选择2011年1-12月长治和平医院诊断为微观肠炎的老年患者116例,分析其临床表现、微观肠炎相关药物服用状况、病理分型及美沙拉嗪短期治疗效果. 结果 老年人微观肠炎占同期老年慢性腹泻患者27.6%,临床表现轻中度水样、黏液便,伴重度腹痛者仅占1.7%.胶原性肠炎与淋巴细胞肠炎型分别为31.9%与68.1%,约50.0%患者有服用微观肠炎相关药物史;美沙拉嗪治疗4周后,

  19. 5-ASA in ulcerative colitis: Improving treatment compliance

    Institute of Scientific and Technical Information of China (English)

    Cosimo Prantera; Marina Rizzi

    2009-01-01

    5-aminosalicylic acid (5-ASA) compounds are a highly effective treatment for ulcerative colitis (UC). While UC patient compliance in clinical studies is over 90%, only 40% of patients in every day life take their prescribed therapy. Adherence to medication has been emphasized recently by a Cochrane meta-analysis that has suggested that future trials of 5-ASA in UC should look at patient compliance rather than drug efficacy. Better compliance can be obtained by reducing the number of tablets and times of administration. Given that the 5-ASA formulations have different delivery systems that split the active moiety in various regions of the intestine, it is particularly important that an adequate dose of the drug arrives at the inflamed part of the colon. 5-ASA Multi matrix (MMx) is a novel, high strength (1.2 g), oral formulation designed for once-daily dosing. It releases the active moiety throughout the colon. Different studies with this compound have shown that it is as effective as 5-ASA enema in the treatment of mild-to-moderate, left-sided UC, and is comparable to a pH-dependent, delayed release 5-ASA (Asacol(R)), even if given once daily. Recently, the effectiveness in the acute phase of UC has been confirmed also in maintenance. In conclusion, at present, 5-ASA MMx seems theoretically the best agent for maintaining patient compliance, and consequently, treatment effectiveness.

  20. Rationale and design of a study exploring the efficacy of once-daily oral rivaroxaban (X-TRA) on the outcome of left atrial/left atrial appendage thrombus in nonvalvular atrial fibrillation or atrial flutter and a retrospective observational registry providing baseline data (CLOT-AF).

    Science.gov (United States)

    Lip, Gregory Y H; Hammerstingl, Christoph; Marin, Francisco; Cappato, Riccardo; Meng, Isabelle Ling; Kirsch, Bodo; Morandi, Eolo; van Eickels, Martin; Cohen, Ariel

    2015-04-01

    There are still many unresolved issues concerning patient outcomes and prognostic factors in patients with atrial fibrillation (AF) and left atrial/left atrial appendage (LA/LAA) thrombi. Rivaroxaban (Xarelto®), a potent and highly selective oral, direct factor Xa inhibitor, is a new therapeutic option in this setting. The planned study program will consist of a prospective interventional study (X-TRA) and a retrospective observational registry (CLOT-AF). The primary objective of the X-TRA study is to explore the efficacy of rivaroxaban in the treatment of LA/LAA thrombi in patients with nonvalvular AF or atrial flutter, scheduled to undergo cardioversion or AF ablation, in whom an LA/LAA thrombus has been found on transesophageal echocardiography (TEE) before the procedure. The primary end point is the complete LA/LAA thrombus resolution rate at 6 weeks of end of treatment confirmed by TEE. The secondary objectives are to describe categories of thrombus outcome in patients (resolved, reduced, unchanged, larger, or new) confirmed on TEE at the end of treatment (after 6 weeks of treatment), incidence of the composite of stroke and noncentral nervous system systemic embolism at the end of treatment and during follow-up, and incidence of all bleeding at the end of treatment and during follow-up. The objective of the CLOT-AF registry is to provide retrospective thrombus-related patient outcome data after standard-of-care anticoagulant treatment in patients with nonvalvular AF or atrial flutter, who have TEE-documented LA/LAA thrombi. The data will be used as a reference for the prospective X-TRA study. In conclusion, X-TRA and CLOT-AF will provide some answers to the many unresolved issues concerning patient outcomes and prognostic factors in patients with AF and LAA thrombi. Results from this study program would provide the first prospective interventional study (X-TRA) and a large international retrospective observational registry (CLOT-AF) on the prevalence and natural history of LA/LAA thrombi. Unique data on clot resolution with rivaroxaban in a prospective cohort would be obtained in X-TRA. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  1. Trapping of the malaria vector Anopheles gambiae with odour-baited MM-X traps in semi-field conditions in western Kenya

    NARCIS (Netherlands)

    Njiru, B.N.; Mukabana, W.R.; Takken, W.; Knols, B.G.J.

    2006-01-01

    Background - The successful development of odour-baited trapping systems for mosquitoes depends on the identification of behaviourally active semiochemicals, besides the design and operating principles of such devices. A large variety of 'attractants' has been identified in laboratory investigations

  2. A new angle for glp-1 receptor agonist: the medical economics argument. Editorial on: Huetson P, Palmer JL, Levorsen A, et al. Cost-effectiveness of the once-daily glp-1 receptor agonist lixisenatide compared to bolus insulin both in combination with basal insulin for the treatment of patients with type 2 diabetes in Norway. J Med Econ 2015: 1-13 [Epub ahead of print].

    Science.gov (United States)

    Valencia, Willy Marcos; Florez, Hermes Jose

    2015-01-01

    Glucagon-like peptide-1 receptor agonists (GLP-1 RA) are relatively new medications for diabetes that offer a weight-loss profile that can be considered desirable for patients with both type 2 diabetes (T2D) and obesity. GLP-1 RA are effective in combination with insulin, and even slightly superior or at least equal to short-acting insulin in T2D; however, since they work in the incretin system, they may not be effective in long-standing disease. Additionally, only recently have publications reported their cardiovascular safety, and there is limited evidence for long-term effectiveness. The work presented by Huetson et al. offers a much needed perspective through a medical economic model for the long term cost-effectiveness of GLP-1 RA. The authors found benefits in quality-adjusted life years and reduced lifetime healthcare costs. While there are a few limitations, this study contributes to the understanding of these agents and their impact on the epidemics of obesity in T2D, where weight management is no longer an option, but an essential component of the diabetes plan of care.

  3. Balsalazide

    Science.gov (United States)

    ... drug. It is converted in the body to mesalamine and works by reducing bowel inflammation, diarrhea, rectal ... salicylate (Nuprin Backache, Mobidin, Extra Strength Doan's, others), mesalamine (Asacol, Pentasa, Rowasa), salsalate (Argesic-AS, Disalcid, others), ...

  4. φ88.9 mm×6.45 mm 110S油管断裂原因分析%Fracture Analysis of φ88.9 mmx6.45 mm 110S Tubing

    Institute of Scientific and Technical Information of China (English)

    乔学华

    2013-01-01

    对某井φ88.9 mm×6.45 mm 110S油管断裂事故进行了深入调查研究,分析了4根两两相互匹配的断裂油管样品,对断口形貌、管体几何参数、理化性能、金相组织和腐蚀产物等进行了试验分析.结果表明:φ88.9mm×6.45 mm 110S油管的理化性能均满足API Spec 5CT标准及用户要求;油管断裂机理为H2S应力腐蚀开裂.建议加强H2S现场检测,选择适合的抗H2S油管.

  5. Electron spin resonance study of electron localization and dynamics in metal-molten salt solutions: comparison of M-MX and Ln-LnX sub 3 melts (M alkali metal, Ln = rare earth metal, X = halogen)

    CERN Document Server

    Terakado, O; Freyland, W

    2003-01-01

    We have studied the electron spin resonance (ESR) spectra in liquid K-KCl and M-(NaCl/KCl) sub e sub u sub t mixtures at different concentrations in salt-rich melts approaching the metal-nonmetal transition region. In both systems F-centre-like characteristics are found. Strongly exchange narrowed signals clearly indicate that fast electron exchange occurs on the picosecond timescale. In contrast, the ESR spectra of a (NdCl sub 2)(NdCl sub 3)-(LiCl/KCl) sub e sub u sub t melt are characterized by a large line width of the order of 10 sup 2 mT which decreases with increasing temperature. In this case, the g-factor and correlation time are consistent with the model of intervalence charge transfer, which is supported by recent conductivity and optical measurements. The different transport mechanisms will be discussed.

  6. Inflammatory bowel diseases: Current problems and future tasks.

    Science.gov (United States)

    Actis, Giovanni C; Pellicano, Rinaldo; Rosina, Floriano

    2014-08-06

    Current knowledge on inflammatory bowel disease (IBD) is mainly endorsed by controlled trials and epidemiologic studies. Yet, we seldom look at the messages from real-world practice. Among a patient population followed since 2008, we looked at an unselected sample of 64 IBD patients [26 Crohn's disease (CD) and 38 ulcerative colitis (UC)] who had been seen as out-patients in the last year. Inducing remission, mesalamines (86% for UC/69% for CD/33%-16% as MMX formulation) prevailed as prescriptions; steroids (55%/19% for UC/CD) ranked second. Prescription of third-party drugs (antibiotics, NSAIDs, biologics) and adherence, were issues in the maintenance. 34% of CD, and 23% of UC patients showed accompanying immunologic diseases: CD-associated familiar psoriasis (4:9) ranked first. Main Message. The association between IBD (CD mainly) and psoriasis, now found in our practice, matches current basic science gathering IBD together with psoriasis (and perhaps chronic respiratory disease) under the comprehensive term "barrier organ disease" wherein an epithelial surface with sensor systems rules contacts between outer antigens and a reactive underneath tissue, with the balance between inflammation and quiescence kept at any time by mucosal permeability. IBD is thus viewed as a polyfactorial/polygenic/syndromic disorder, embedded into a galaxy of immune conditions offering multiple points of attack. This mindset of splitting the IBDs into pathogenic categories may allow overcoming the uniformly targeting of a single cytokine by biological drugs, in favor of demarcating the boundaries between different disease-subtype-specific indications, and paving the way to future personalized strategies.

  7. Inflammatory bowel diseases: Current problems and future tasks

    Institute of Scientific and Technical Information of China (English)

    Giovanni; C; Actis; Floriano; Rosina; Rinaldo; Pellicano

    2014-01-01

    Current knowledge on inflammatory bowel disease(IBD)is mainly endorsed by controlled trials and epidemiologic studies. Yet,we seldom look at the messages from real-world practice. Among a patient population followed since2008,we looked at an unselected sample of 64 IBD patients [26 Crohn’s disease(CD) and 38 ulcerative colitis(UC)] who had been seen as out-patients in the last year.Inducing remission,mesalamines(86% for UC/69% for CD/33%-16% as MMX formulation) prevailed as prescrip-tions; steroids(55%/19% for UC/CD) ranked second.Prescription of third-party drugs(antibiotics,NSAIDs,biologics) and adherence,were issues in the maintenance.34% of CD,and 23% of UC patients showed accompany-ing immunologic diseases: CD-associated familiar psoriasis(4:9) ranked first. Main Message. The association between IBD(CD mainly) and psoriasis,now found in our practice,matches current basic science gathering IBD together with psoriasis(and perhaps chronic respiratory disease) under the comprehensive term "barrier organ disease" wherein an epithelial surface with sensor system srules contacts between outer antigens and a reactive underneath tissue,with the balance between inflammation and quiescence kept at any time by mucosal permeability.IBD is thus viewed as a polyfactorial/polygenic/syndromic disorder,embedded into a galaxy of immune conditions offering multiple points of attack. This mindset of splitting the IBDs into pathogenic categories may allow overcoming the uniformly targeting of a single cytokine by biological drugs,in favor of demarcating the boundaries between different disease-subtype-specific indications,and paving the way to future personalized strategies.

  8. Drug: D00377 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D00377 Drug Mesalazine (JAN/INN); Mesalamine (USP); Apriso (TN); Asacol (TN); Canas...a (TN); Delzicol (TN); Lialda (TN); Mesalamine (TN); Pentasa (TN); Rowasa (TN); Sfrowasa (TN) C7H7NO3 153.04... Digestive organ agents 239 Miscellaneous 2399 Others D00377 Mesalazine (JAN/INN); Mesalamine (USP) Anatomic...TORY AGENTS A07EC Aminosalicylic acid and similar agents A07EC02 Mesalazine D00377 Mesalazine (JAN/INN); Mesa...lamine (USP) USP drug classification [BR:br08302] Inflammatory Bowel Disease Agents Aminosalicylates Mesalamine D00377 Mesa

  9. Progress of colon targeted mesalamine formulations%美沙拉嗪结肠靶向制剂研究进展

    Institute of Scientific and Technical Information of China (English)

    赵亚绘; 张赫然; 王彦竹; 宋丽明; 王杏林; 田沛

    2015-01-01

    美沙拉嗪是近30年来活动期轻中度溃疡性结肠炎的首选用药,具很好的诱导缓解和维持缓解功效.美沙拉嗪只有以原型形式到达结肠病变部位才能发挥治疗效果,而常规制剂口服后迅速被胃肠吸收经肝脏代谢,易产生腹痛、腹泻、肾毒性等不良反应,仅少量到达结肠,已上市结肠靶向美沙拉嗪则极易在小肠过早释药,结肠定位效果较差,因此新型精确美沙拉嗪结肠靶向制剂的研究至关重要.本文主要综述了近年来美沙拉嗪结肠靶向制剂的研究进展,以期为无毒、生物相容、生物可降解、精准结肠靶向的高剂量美沙拉嗪制剂的开发提供参考依据.

  10. Randomised clinical trial: evaluation of the efficacy of mesalazine (mesalamine) suppositories in patients with ulcerative colitis and active rectal inflammation – a placebo‐controlled study

    National Research Council Canada - National Science Library

    Watanabe, M; Nishino, H; Sameshima, Y; Ota, A; Nakamura, S; Hibi, T

    2013-01-01

    ..., and immunosuppressants, among which mesalazine preparations are widely used as standard treatment. For proctitis, mesalazine suppositories are recommended as the first‐line drug for remission induction and maintenance of remission. In addition, oral mesalazine is widely used to treat left‐sided colitis and pancolitis, though concomitant use with a ...

  11. Design, Construction and Testing of Simple Solar Maize Dryer

    OpenAIRE

    Folaranmi, Joshua

    2008-01-01

    This project reports the design, construction and testing of a simple solar maize dryer. It is design in such a way that solar radiation is not incident directly on the maize, but preheated air warmed during its flow through a low pressure thermosphonic solar energy air heater or collector made up of an insulating material (polystyrene) of size 100mmx50mmx25.4mm, absorber plate (aluminium) sheet painted black of size 100mmx50mm and a cover glass (5mm thickness) measuring 100mmx50mm all arrang...

  12. Type Ⅳ secretion system of Xanthomonas campestris pv.campestris is induced in MMX and related to stress resistance%十字花科黑腐病菌Ⅳ型分泌系统的诱导表达与抗逆功能分析

    Institute of Scientific and Technical Information of China (English)

    蒋国凤; 韦蕾蕾; 张正淳; 徐勇; 张君成; 何勇强; 姜伯乐

    2015-01-01

    细菌通过Ⅳ型分泌系统(TypeⅣSecretion System,T4SS)的接合系统、效应物转运系统和释放/吸收系统3个子家族进行DNA、蛋白质及毒素的分泌和转运.十字花科黑腐病菌(Xanthomonas campestris pv.campestris,Xcc)是一种重要的植物病原菌,也是研究植物病原细菌与植物相互作用机理的模式细菌之一.本研究通过检测Xcc 8004野生型菌株和T4SS突变体在不同条件下的生长、诱导情况及对过敏反应的影响发现:T4SS不影响在培养基中的生长,与野生型菌株相比,T4SS突变体在非寄主辣椒ECW-10R上的过敏反应减弱;T4SS相关基因受基本培养基MMX诱导表达,且与Ni2+、H2O2、Phenol等抗逆相关.推测T4SS相关基因在该病原菌的接触、识别阶段起作用.

  13. The effect analysis of Mesalamine combined with enema in the treatment of ulcerative colitis%溃疡性结肠炎应用美沙拉嗪联合灌肠治疗的效果分析

    Institute of Scientific and Technical Information of China (English)

    李莉; 陈洁; 刘春燕; 张军

    2014-01-01

    目的 探究溃疡性结肠炎应用美沙拉嗪联合灌肠治疗的效果.方法 选择2011年7月~2013年7月湖州市中心医院溃疡性结肠炎患者76例为研究对象,按随机数字表方法将其分成对照组和研究组,每组各38例.对照组给予柳氮磺胺毗啶口服治疗,研究组给予美沙拉嗪的缓释颗粒口服联合灌肠治疗.分析两组患者的临床治疗效果、黏膜组织变化和不良反应情况.结果 研究组患者治疗的有效率为94.74%,高于对照组(73.68%),差异有统计学意义(P<0.05);结肠镜下观察,研究组黏膜组织总改善率为97.37%,高于对照组(78.95%),差异有统计学意义(P<0.05);研究组患者的不良反应发生率(5.26%)低于对照组(21.05%),差异有统计学意义(P<0.05).结论 对溃疡性结肠炎患者予以美沙拉嗪的缓释颗粒口服联合灌肠治疗,能够有效提升临床疗效,并降低不良反应的发生,具有一定临床应用和研究价值.

  14. Mesalamine combined with Kangfuxin Liquid in the treatment of ulcerative colitis: a Meta-analysis%美沙拉嗪颗粒联合康复新液治疗溃疡性结肠炎的Meta分析

    Institute of Scientific and Technical Information of China (English)

    牛斌斌; 叶树凤; 陈宝余; 张明; 何栋钢; 王祥

    2014-01-01

    目的 系统评价口服美沙拉嗪颗粒联合康复新液(美洲大蠊干燥虫体的乙醇提取物)灌肠治疗溃疡性结肠炎的疗效.方法 计算机检索国内文献数据库(时限均从建库开始至2013年11月)相关的随机对照试验,使用Rev-Man 5.2软件进行Meta分析.结果 最终纳入11个研究,889例患者,其中美沙拉嗪联合康复新液组451例,美沙拉嗪组438例.Meta分析结果显示,美沙拉嗪联合康复新液组的总有效率(RR=1.16,95% CI:1.10~ 1.21,P<0.00001)、治愈率(RR=1.63,95%CI:1.28~2.07,P<0.000 01)以及肠黏膜改善率(RR=1.20,95%CI:1.08~1.34,P<0.000 01)均高于美沙拉嗪组.结论 口服美沙拉嗪联合康复新液灌肠治疗溃疡性结肠炎的疗效明显优于美沙拉嗪.

  15. Determination of Related Substances in Mesalamine Extended Release Capsules by HPLC%高效液相色谱法测定美沙拉嗪控释胶囊的有关物质

    Institute of Scientific and Technical Information of China (English)

    郑小丹; 高丽; 王锦刚

    2012-01-01

    目的:建立一种高效液相色谱法测定美沙拉嗪缓释胶囊的3-氨基水杨酸等有关物质.方法:采用HPLC法.色谱柱为Thermo BDS C8柱(4.6mm×250mm,5μm).流动相为磷酸盐缓冲液(取磷酸二氢钾1.36g和辛烷磺酸钠2.2g,加水溶解至890ml,用磷酸调节pH至2.2)-甲醇-乙腈(890∶80∶30),柱温30℃,流速1.2ml·min-1,检测波长为220nm.结果:3-氨基水杨酸在0.1994 ~1.994μg/mL浓度范围内与峰面积呈良好线性关系,r=1.0000.平均回收率96.38%,RSD为1.71%;定量限为86.69ng/ml.结论:本方法简便、灵敏、准确,能用于美沙拉嗪缓释胶囊有关物质的质量控制.

  16. Clinical effects of Deanxit combing with Mesalamine on rotavirus enteritis%黛力新和美沙拉嗪合并使用治疗结肠炎患者的临床效果评价

    Institute of Scientific and Technical Information of China (English)

    戈弋巾; 王颖; 唐文; 李聪; 王超萍

    2014-01-01

    目的:观察黛力新结合美沙拉嗪合治疗结肠炎的临床效果,探究其联合应用价值.方法:将70例确诊为结肠炎的患者随机分为两组,对照组35例采用常规治疗,实验组35例在其基础上加上黛力新结合美沙拉嗪合进行治疗,观察其治疗效果和病程时间,并进行比较.结果:治疗后,观察组大肠杆菌数量明显减少,差异具有统计学意义(P<0.05);实验组的转阴率(58.05%)明显高于对照组(30.65%);实验组的病程较照组缩短.结论:黛力新结合美沙拉嗪合治疗结肠炎的治疗效果比常规的方案更加有效,并且可以缩短病程,及时治愈,降低患者的并发症风险和危害.

  17. Probiotics combined with mesalamine in treatment of ulcerative colitis: efficacy and safety observation%益生菌联合美沙拉秦治疗溃疡性结肠炎的疗效和安全性观察

    Institute of Scientific and Technical Information of China (English)

    庞智; 李宁; 丁海燕; 刘志峰; 李旸; 韩晓

    2016-01-01

    目的 探讨益生菌联合美沙拉秦对轻、中度活动期溃疡性结肠炎患者的临床疗效和安全性以及比较患者治疗前后实验室多种指标的改变.方法 42例确诊的轻、中度溃疡性结肠炎患者,采用随机对照的研究方法分为两组.其中治疗组(养乐多1瓶/次+艾迪莎1 g/次、1日3次)20例,对照组(艾迪莎1 g/次、1日3次)22例,共观察6个月.治疗前、后两组患者临床表现、安全性和实验室多种指标也进行比较.结果 治疗组临床治疗总有效率为90.00%,对照组为81.82%,治疗组临床完全缓解率为45.00%,对照组为31.82%,治疗组的完全缓解率和总有效率均显著高于对照组(x2值分别为57.48、59.42,P<0.05),前者总复发率显著低于后者(x2=58.65,P<0.05).且治疗中未见不良反应和副作用.治疗组治疗6个月后血红蛋白、红细胞压积和白蛋白水平均显著升高(t值分别为2.82、2.21、2.18,P<0.05),而对照组在治疗后血红蛋白、白蛋白和红细胞压积均没有发生明显改变(t值分别为0.10、0.11、0.20,P>0.05);治疗组的血沉和c-反应蛋白均非常显著下降(t值分别为5.17、4.87,P<0.01),而对照组血沉和c-反应蛋白均显著下降(t值分别为3.01、2.43,P<0.05);治疗组的血清 TNF-α、IL-17和IL-23细胞因子出现非常显著下降(t值分别为3.39、5.98、12.19,P<0.01),而对照组的血清TNF-α、IL-17和IL-23细胞因子出现显著下降(t值分别为2.33、2.59、11.37,P<0.05);治疗6个月后两组间上述指标差异均有统计学意义(t值分别为2.92、2.23、2.09、2.09、2.34、2.26、2.78、2.71,P<0.05),治疗组血红蛋白、红细胞压积和白蛋白水平均显著高于对照组,血沉和c-反应蛋白均显著低于对照组,治疗组的血清TNF-α、IL-17和IL-23细胞因子均显著低于对照组.结论 益生菌联合美沙拉秦对轻、中度活动期溃疡性结肠炎患者比单用美沙拉秦更能显著地降低促炎症性细胞因子水平,诱导活动期溃疡性结肠炎的缓解作用和维持缓解作用更强,显示出良好的安全性和有效的治疗效果,表明该益生菌对溃疡性结肠炎具有良好的辅助治疗作用.

  18. The pharmacokinetics and bioavailability of mesalamine enteric-coated tablets in healthy volunteers%美沙拉嗪肠溶片在健康人体的药代动力学及生物等效性研究

    Institute of Scientific and Technical Information of China (English)

    顾建琴; 石劲敏; 唐黎明; 李雪宁

    2007-01-01

    目的:研究进口美沙拉嗪(5-ASA)肠溶片在健康人体的药代动力学,并与国产片剂进行生物等效性比较.方法:18名健康男性受试者分别随机交叉口服美沙拉嗪肠溶片试验药或参比药0.5 g,每8小时一次,连续七次.用柱前衍生化-HPLC-荧光法测定给药后不同时间点血浆中5-ASA和其活性代谢产物乙酰化-5-氨基水杨酸(Ac-5-ASA)的浓度,计算药代动力学参数并评价两种制剂的生物等效性.结果:试验药及参比药的原形药(5-ASA)的药代动力学参数分别为:AUC0-t 10.25±3.96和9.45±2.94 μg·h·ml-1;Cmax 2.21±1.49和1.98±1.18 μg·ml-1;tmax 4.83±2.32和4.47±3.15 h.其代谢产物(Ac-5-ASA)的药代动力学参数分别为:AUC0-t 30.29±8.62和29.90±7.45μg·h·ml-1;Cmax 3.21±1.02和3.28±1.20μg·ml-1;tmax5.94±2.54和4.31±3.29 h.经统计分析,上述各项参数间差别均无显著性意义(p>0.05).进口美沙拉嗪肠溶片相对生物利用度为(108.4±27.4%).结论:美沙拉嗪肠溶片试验药与参比药具有生物等效性.

  19. 双歧三联活菌联合美沙拉唪治疗溃疡性结肠炎疗效观察%Clinical Observation of Bifid Triple Viable Capsules with Mesalamine in the Treatment of Ulcerative Colitis

    Institute of Scientific and Technical Information of China (English)

    2016-01-01

    目的 观察双歧三联活菌联合美沙拉嗪治疗溃疡性结肠炎(UC)的临床疗效.方法 选取收治的UC患者102例,随机分为对照组和观察组各51例,观察组给予美沙拉嗪及双歧三联活菌口服,对照组只给予美沙拉嗪口服.观察两组的疗效及治疗前后的炎性细胞因子和凝血参数等变化.结果 观察组治疗总有效率达96.07%,而对照组仅为82.35%,两组比较差异具有统计学意义(P<0.05);观察组治疗后TNF-α、IL-6、IL-1、IL-8均低于对照组,Fib 、MPV指标值均高于对照组,差异均具有统计学意义(P<0.05).结论 双歧三联活菌联合美联合美沙拉嗪治疗溃疡性结肠炎的临床疗效优于单纯使用美沙拉嗪,具有临床运用价值.

  20. 美沙拉嗪联合益阳愈溃汤治疗溃疡性结肠炎疗效分析%Therapeutic Efficacy of Mesalamine with Yiyang Ulcer Decoction in the Treatment of Ulcerative Colitis

    Institute of Scientific and Technical Information of China (English)

    杜修坤; 黄如川; 符智深; 周婷; 吴云清

    2015-01-01

    目的:探讨美沙拉嗪联合益阳愈溃汤治疗溃疡性结肠炎的疗效.方法:根据治疗方案将119例溃疡性结肠炎患者分为观察组(63例)与对照组(56例),观察组患者在常规治疗基础上联合使用美沙拉嗪、益阳愈溃汤治疗,对照组患者在常规治疗基础上联合使用美沙拉嗪治疗.结果:①治疗前,两组患者溃疡性结肠炎活动指数(UCAI)、C反应蛋白(CRP)、血沉(ESR)相比差异无统计学意义(P>0.05);治疗后,观察组UCAI、CRP、ESR显著低于对照组,差异有统计学意义(P<0.05).②观察组发热、脓血便、腹痛、腹泻等临床症状消失时间显著低于对照组,差异有统计学意义(P<0.05).③经疗效评价,观察组指标效果显著优于对照组,差异有统计学意义(P<0.05).结论:美沙拉嗪联合益阳愈溃汤治疗溃疡性结肠炎的疗效确切且恢复快,值得临床推广应用.

  1. 美沙拉嗪栓剂在健康人体的药代动力学及生物等效性%Pharmacokinetics and bioequivalence of mesalamine suppository in healthy volunteers

    Institute of Scientific and Technical Information of China (English)

    徐红蓉; 李雪宁; 陈伟力; 顾建琴

    2004-01-01

    目的研究进口美沙拉嗪(5-ASA)栓剂的药代动力学过程及其生物等效性.方法1 8名健康男性受试者用随机交叉给药方案,分别单次直肠给与美沙拉嗪栓剂试验药和参比药2 g,用柱前衍生化一HPLC一荧光法测定给药后不同时间点血浆中5-ASA和其活性代谢产物乙酰化-5-氨基水杨酸(Ac-5-ASA)的浓度,评价两种制剂的生物等效性.结果试验药及参比药的原形药(5-ASA):AUC0-t分别为3.20±2.35和3.34±2.83 μg.h.mL-1;AUC0-∞分别为3.22±2.37和3.38±2.89 μg.h.mL-1;Cmax分别为0.48±0.16和0.42±0.17 μg.mL-1;tmax分别为4.61±2.8和5.72±3.30 h;t1/2分别为3.6 6±1.44和3.97±2.24 h.其代谢产物(Ac-5-ASA):AUCo-t分别为9.68±6.26和10.26±7.53μg.h.mL-1; AUC0-∞分别为10.01±6.79和10.74±8.57 μg.h.mL-1;Cmax分别为1.23±0.41和1.10±0.37 μg.mL-1; tmax分别为5.00±2.20和6.11±3.48 h;t1/2分别为5.99±3.33和6.64±4.22 h.经统计学处理,上述各项参数间差别均无显著性意义(P>0.05).美沙拉嗪栓剂相对生物利用度为(103.7±19.4)%.结论美沙拉嗪栓剂试验药与参比药具有生物等效性.

  2. Effect of HPMC - E15 LV premium polymer on release profile and compression characteristics of chitosan/ pectin colon targeted mesalamine matrix tablets and in vitro study on effect of pH impact on the drug release profile.

    Science.gov (United States)

    Newton, A M J; Lakshmanan, Prabakaran

    2014-04-01

    The study was designed to investigate the in vitro dissolution profile and compression characteristics of colon targeted matrix tablets prepared with HPMC E15 LV in combination with pectin and Chitosan. The matrix tablets were subjected to two dissolution models in various simulated fluids such as pH 1.2, 6, 6.8, 7.2, 5.5. The fluctuations in colonic pH conditions during IBD (inflammatory bowel disease) and the nature of less fluid content in the colon may limit the expected drug release in the polysaccharide-based matrices when used alone. The Hydrophilic hydroxyl propyl methylcellulose ether premium polymer (HPMC E15 LV) of low viscosity grade was used in the formulation design, which made an excellent modification in physical and compression characteristics of the granules. The release studies indicated that the prepared matrices could control the drug release until the dosage form reaches the colon and the addition HPMC E15 LV showed the desirable changes in the dissolution profile by its hydrophilic nature since the colon is known for its less fluid content. The hydrophilic HPMC E15 LV allowed the colonic fluids to enter into the matrix and confirmed the drug release at the target site from a poorly water soluble polymer such as Chitosan and also from water soluble Pectin. The dramatic changes occurred in the drug release profile and physicochemical characteristics of the Pectin, Chitosan matrix tablets when a premium polymer HPMC E15 LV added in the formulation design in the optimized concentration. Various drug release mechanisms used for the examination of drug release characteristics. Drug release followed the combined mechanism of diffusion, erosion, swelling and polymer entanglement. In recent decade, IBD attracts many patents in novel treatment methods by using novel drug delivery systems.

  3. An allene-doped liquid argon ionization chamber for Ar and Ca ions at around 100 MeV/n

    CERN Document Server

    Yunoki, A; Fukuda, N; Kase, M; Kato, T; Kikuchi, J; Masuda, K; Niimura, M; Okada, H; Ozaki, K; Piao, Y; Shibamura, E; Tanaka, M; Tanihata, I; Terasawa, K

    1999-01-01

    An allene-doped liquid argon ionization chamber with 48 mmx48 mmx40 mm sensitive volume has been constructed for precise energy measurement of heavy ions at around 100 MeV/n. An energy resolution of 0.6%-0.7% (FWHM) was achieved for Ca and Ar ions both at 78 MeV/n. (author)

  4. Oral rivaroxaban for the prevention of symptomatic venous thromboembolism after elective hip and knee replacement

    DEFF Research Database (Denmark)

    Eriksson, B I; Kakkar, A K; Turpie, A G G;

    2009-01-01

    A once-daily dose of rivaroxaban 10 mg, an oral, direct Factor Xa inhibitor, was compared with enoxaparin 40 mg subcutaneously once daily for prevention of venous thromboembolism in three studies of patients undergoing elective hip and knee replacement (RECORD programme). A pooled analysis of dat...

  5. 21 CFR 520.2098 - Selegiline hydrochloride tablets.

    Science.gov (United States)

    2010-04-01

    ... use—Dogs—(1) Dosage. 1 milligram per kilogram (0.45 milligram per pound) of body weight. (i... kilogram once daily. Federal law restricts this drug to use by or on the order of a licensed veterinarian. (2) Dosage. 0.5 to 1.0 milligram per kilogram of body weight once daily. (i) Indications for use....

  6. COMPARISON OF TREATMENT WITH LISINOPRIL VERSUS ENALAPRIL FOR CONGESTIVE-HEART-FAILURE

    NARCIS (Netherlands)

    ZANNAD, F; VANDENBROEK, SAJ; BORY, M

    1992-01-01

    The effect of lisinopril 5-20 mg once daily or enalapril 5-20 mg once daily on exercise capacity, ventricular ectopic activity, and signs and symptoms of heart failure have been studied in 278 patients with mild-to-moderate (New York Heart Association [NYHA] classes II and III) heart failure in a ra

  7. Efficacy, nephrotoxicity and ototoxicity of aminoglycosides, mathematically modelled for modelling-supported therapeutic drug monitoring

    NARCIS (Netherlands)

    Croes, Sander; Koop, Arjen H.; van Gils, Stephanus A.; Neef, Cees

    Therapeutic drug monitoring (TDM) of aminoglycosides has been a topic during the last thirty years. There is a tendency that – because of the once-daily regimen – TDM is considered not necessary anymore. Although once daily dosing has the potential for decreased toxicity, long-term usage can cause

  8. Antiandrogen monotherapy in patients with localized or locally advanced prostate cancer

    DEFF Research Database (Denmark)

    Iversen, Peter; McLeod, David G; See, William A;

    2010-01-01

    To evaluate the efficacy and tolerability of bicalutamide 150 mg once-daily as immediate hormonal therapy in patients with prostate cancer or as adjuvant to radical prostatectomy or radiotherapy.......To evaluate the efficacy and tolerability of bicalutamide 150 mg once-daily as immediate hormonal therapy in patients with prostate cancer or as adjuvant to radical prostatectomy or radiotherapy....

  9. Anti-inflamatory dose doxycycline in the treatment of rosacea.

    Science.gov (United States)

    Del Rosso, James Q

    2009-07-01

    Anti-inflammatory dose doxycycline (ADD), which is the administration of doxycycline 40 mg extended-release capsule once daily, is the only oral therapy approved by the United States Food and Drug Administration (FDA) for treatment of rosacea. ADD once daily has been shown to exhibit anti-inflammatory activity while not demonstrating evidence of antibiotic effects, including with chronic administration. This article summarizes the clinical studies to date on the use of ADD once daily in papulopustular rosacea, including both monotherapy and combination therapy studies. The combination therapy approach of ADD once daily and metronidazole gel 1% once daily has been shown to exhibit a more rapid onset of therapeutic effect than topical therapy alone. ADD once daily has been demonstrated to be effective in adult subjects with moderate to severe rosacea, and exhibits a favorable safety profile coupled with absence of antibiotic selection pressure. Additionally, a much lower incidence of gastrointestinal side effects has been noted with ADD once daily as compared to doxycycline 100 mg once daily.

  10. Analysis of rumen motility patterns using a wireless telemetry system to characterize bovine reticuloruminal contractions

    Science.gov (United States)

    The objective of this study was to characterize rumen motility patterns of cattle fed once daily. Eight ruminally-cannulated Holstein steers (BW = 321 ± 11 kg) were fed alfalfa cubes once daily at 1.5 × NEm top-dressed with a TM-salt pre-mix. Three 24-h collection periods were conducted and each com...

  11. Effects of biphasic, basal-bolus or basal insulin analogue treatments on carotid intima-media thickness in patients with type 2 diabetes mellitus

    DEFF Research Database (Denmark)

    Lundby-Christensen, Louise; Vaag, Allan; Tarnow, Lise;

    2016-01-01

    in combination with insulin detemir once daily (n=138) versus insulin detemir alone once daily (n=137), aiming at HbA1c≤7.0% (≤53 mmol/mol). OUTCOMES: Primary outcome was change in mean carotid IMT (a marker of subclinical cardiovascular disease). HbA1c, insulin dose, weight, and hypoglycaemic and serious...

  12. Clopidogrel, a novel antiplatelet agent, and digoxin : Absence of pharmacodynamic and pharmacokinetic interaction

    NARCIS (Netherlands)

    Peeters, PAM; Crijns, HJMJ; Tamminga, WJ; Jonkman, JHG; Dickinson, JP; Necciari, J

    1999-01-01

    The safety, and the pharmacodynamic and pharmacokinetic compatibility of clopidogrel, 75 mg daily, with the cardiac glycoside digoxin, were assessed in 12 healthy male subjects who took digoxin 0.25 mg once daily for 20 days and, in addition, clopidogrel 75 mg once daily from day 11 to day 20, so as

  13. Design, Construction and Testing of Simple Solar Maize Dryer

    Directory of Open Access Journals (Sweden)

    Joshua FOLARANMI

    2008-12-01

    Full Text Available This project reports the design, construction and testing of a simple solar maize dryer. It is design in such a way that solar radiation is not incident directly on the maize, but preheated air warmed during its flow through a low pressure thermosphonic solar energy air heater or collector made up of an insulating material (polystyrene of size 100mmx50mmx25.4mm, absorber plate (aluminium sheet painted black of size 100mmx50mm and a cover glass (5mm thickness measuring 100mmx50mm all arranged in this order contributed to the heating. The test results gave temperature above 45OC in the drying chamber, and the moisture content of 50kg of maize reduced to about 12.5% in three days of 9hours each day of drying.

  14. A new DOI detector design using discrete crystal array with depth-dependent reflector patterns and single-ended readout

    Science.gov (United States)

    Lee, Seung-Jae; Lee, Chaeyeong; Kang, Jihoon; Chung, Yong Hyun

    2017-01-01

    We developed a depth of interaction (DOI) positron emission tomography (PET) detector using depth-dependent reflector patterns in a discrete crystal array. Due to the different reflector patterns at depth, light distribution was changed relative to depth. As a preliminary experiment, we measured DOI detector module crystal identification performance. The crystal consisted of a 9×9 array of 2 mmx2 mmx20 mm lutetium-yttrium oxyorthosilicate (LYSO) crystals. The crystal array was optically coupled to a 64-channel position-sensitive photomultiplier tube with a 2 mmx2 mm anode size and an 18.1 mmx18.1 mm effective area. We obtained the flood image with an Anger-type calculation. DOI layers and 9×9 pixels were well distinguished in the obtained images. Preclinical PET scanners based on this detector design offer the prospect of high and uniform spatial resolution.

  15. Submucous colon lipoma: A case report and review of the literature

    Institute of Scientific and Technical Information of China (English)

    Hong Zhang; Jin-Chun Cong; Chun-Sheng Chen; Lei Qiao; En-Qing Liu

    2005-01-01

    Colon lipoma is remarkably rare in clinical practice. We reported a case of ascending colon lipoma in an 83-yearold woman. She was asymptomatic with a lipoma of 35 mmx30 mmx24 mm in size which was found by routine colonoscopy. Right hemicolectomy was performed uneventfully. The diagnosis was made by histological examination. Reviewing the literature and combining with our experience, we discussed the clinical features, diagnosis and treatment of this uncommon disease.

  16. Effect of GLP-1 receptor agonists on waist circumference among type 2 diabetes patients: a systematic review and network meta-analysis.

    Science.gov (United States)

    Sun, Feng; Wu, Shanshan; Guo, Shuxia; Yu, Kai; Yang, Zhirong; Li, Lishi; Zhang, Yuan; Ji, Linong; Zhan, Siyan

    2015-04-01

    Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly used in patients with type 2 diabetes. However, the effect on abdominal obesity has not yet been confirmed. The study aimed to systematically evaluate the effect of GLP-1RAs on waist circumference in patients with type 2 diabetes. MEDLINE, EMBASE, the Cochrane library and www.clinicaltrialgov were searched through October 31, 2013. Randomized controlled trials with available data were selected if they compared GLP-1 RAs with placebo and traditional anti-diabetic drugs with a duration≥8 weeks. Weighted mean difference was estimated using random-effect model. Network meta-analysis was performed to supplement direct comparisons. Seventeen trials with 12 treatments were included. Overall, significant reductions on waist circumference following treatment of liraglutide--1.8 mg once daily (-5.24 cm, 95% CI -7.68, -2.93), liraglutide--1.2 mg once daily (-4.73 cm, 95% CI -6.68, -2.65) and exenatide--10 μg twice daily (-1.34 cm, 95 % CI -2.00, -0.75) were detected versus placebo. The reduction effect was more evident when compared with insulin and thiazolidinediones (range -1.71 to -8.03 cm). Compared with exenatide, liraglutide--0.6 mg once daily, taspoglutide, liraglutide--1.2 mg once daily and liraglutide--1.8 mg once daily significantly decreased waist circumference from -3.32 to -6.01 cm. Besides, liraglutide--1.8 mg once daily significantly decreased waist circumference by -1.73 cm (95 % CI -3.04, -0.55) versus sitagliptin, whereas no significant difference following liraglutide--1.2-mg-once-daily treatment was detected compared with liraglutide--1.8 mg once daily and sitagliptin. Reduction was observed with statistical significance for exenatide--10 μg twice daily compared with exenatide--5 μg twice daily (-1.21 cm, 95% CI -2.43, -0.06). Ranking probability analysis indicated liraglutide--1.8 mg once daily and liraglutide--1.2 mg once daily decreased waist circumference most among all 12

  17. Perianal lotion Joint Mesalamine Furoate Treatment Perianal Genital Eczema Randomized Controlled Study%肛周洗液联合美沙拉嗪、糠酸莫米松治疗肛周外阴湿疹随机平行对照研究

    Institute of Scientific and Technical Information of China (English)

    李建国

    2015-01-01

    [目的]观察肛周洗液联合美沙拉嗪、糠酸莫米松治疗肛周外阴湿疹疗效.[方法]使用随机平行对照方法,将110例门诊患者按就诊顺序号法简单随机分为两组.对照组55例糠酸莫米松乳膏,适量患处局部外搽,2次/d;美沙拉嗪栓,0.25g/次,3次/d,纳肛;0.9%生理盐水洗,坐浴10min.治疗组55例肛周洗液熏洗(苦参、蒲公英各20g,百部、黄柏、白鲜皮各30g,地肤子、蛇床子、枯矾、花椒各10g),1剂/d,冷水浸泡30min,水煎1000mL,过滤取汁,温度降至35~40℃时,熏蒸坐浴10min,2次/d;西药治疗同对照组.连续治疗7d为1疗程.观测临床症状、皮损面积、不良反应.连续治疗4疗程,判定疗效.[结果]治疗组痊愈37例,有效16例,无效2例,总有效率96.32%.对照组痊愈33例,有效14例,无效8例,总有效率85.45%.治疗组疗效优于对照组(P<0.05).两组皮损两组面积均有改善(P<0.01),治疗组改善优于对照组(P<0.01).[结论]肛周洗液联合美沙拉嗪、糠酸莫米松治疗肛周外阴湿疹疗效满意,无严重不良反应,值得推广.

  18. 甘草泻心汤联合美沙拉嗪对溃疡性结肠炎患者血清炎症因子水平的影响及疗效观察%Influence and curative effection of glycyrrhizae decoction for purging stomach fire combined with mesalamine on serum inflammatory factors levels of patients with ulcerative colitis

    Institute of Scientific and Technical Information of China (English)

    郑莲莲

    2015-01-01

    [目的]探讨甘草泻心汤联合美沙拉嗪对溃疡性结肠炎(UC)患者血清炎症因子水平的影响及疗效观察.[方法]选取活动期UC患者86例,按照就诊门诊号顺序其分为实验组和对照组各43例.实验组予以美沙拉嗪肠溶片联合甘草泻心汤,对照组予以单纯的美沙拉嗪肠溶片,2组均连用6周,其中美沙拉嗪肠溶片1.0 g/次,4次/d,口服;甘草泻心汤,1剂/d,煎煮法取汁200 ml,分早晚二次口服.观察并比较治疗前后血清IL-6和10、TNF-α水平的变化,并评估其临床疗效.[结果]治疗6周后,2组血清IL-6和TNF-α水平较前明显下降,IL-10水平较前明显上升(P<0.05或P<0.01),且实验组改善幅度较对照组更明显(P<0.05);同时在临床总有效率方面实验组明显高于对照组(x2 =4.07,P<0.05).[结论]甘草泻心汤联合美沙拉嗪治疗UC的疗效较佳,能明显改善其临床症状,促进肠黏膜的愈合,作用机制可能与其能降低血清IL-6和TNF-α水平,提高血清IL-10水平,调节体内促炎症因子/抗炎症因子比例紊乱,减轻肠黏膜炎症反应密切相关.

  19. The efficacy and safety of mesalamine controlled-release agent for the treatment of inflammatory bowel disease (IBD)%美沙拉嗪控释剂治疗炎症性肠病(IBD)的疗效和安全性

    Institute of Scientific and Technical Information of China (English)

    张惠林

    2012-01-01

    目的 探讨美沙拉嗪控释剂治疗炎症性肠病的临床效果和安全性.方法 选择2010年5月至2011年6月在我院确诊为炎症性肠病的患者54例,随机分为治疗组和对照组各27例,分别服用美沙拉嗪控释剂(1g/次,1次/d)和柳氮磺吡啶(1g/次,3次/d),疗程为8周.结果 治疗组8周后总有效率81.48%(显效12例、有效10例、无效5例),不良反应发生率4.1%;对照组8周后总有效率66.67%(显效8例、有效10例、无效9例),不良反应发生率22.2%,两组总有效率及不良反应发生率比较有统计学差异(P<0.05).结论 美沙拉嗪控释剂对炎症性肠炎疗效确切,不良反应少,安全性较好.

  20. 美沙拉嗪联合双歧三联活菌对溃疡性结肠炎患者TNF-α、IL-8及IL-10水平的影响%Influence of Mesalamine Combined with Bifid Triple Viable on Levels of TNF-α, IL-8 and IL-10 of Patients with Ulcerative Colitis

    Institute of Scientific and Technical Information of China (English)

    童霞; 骆成俊; 许晓梅; 朱晓娟; 张红

    2015-01-01

    目的:探讨美沙拉嗪联合双歧三联活菌治疗溃疡性结肠炎(UC)的临床疗效及对患者TNF-α、IL-8及IL-10水平的影响.方法:选择2013年1月~2014年1月我院收治的UC患者60例,随机分为研究组与对照组,每组30例.对照组患者应用美沙拉嗪治疗,研究组在此基础上联合双歧三联活菌治疗.观察两组临床疗效、血清TNF-α、IL-8及IL-10水平变化及药物不良反应.结果:研究组治疗的总有效率为86.67%,显著高于对照组的63.33%(P <0.05);治疗后,两组TNF-α、IL-8水平显著降低,IL-10水平显著升高(均P<0.01),研究组TNF-α、IL-8显著低于对照组,IL-10水平显著高于对照组(均P<0.05);研究组不良反应发生率为6.67%,明显低于对照组的33.33%(P<0.05).结论:美沙拉嗪联合双歧三联活菌对UC患者黏膜的保护作用显著,且有效抑制UC相关的炎性反应,安全可靠,适于临床推广与应用.

  1. 枯草杆菌二联活菌联合美沙拉嗪治疗溃疡性结肠炎的疗效观察%Clinical Effect of Bacillus Subtilis Double Live Bacteria Enteric-coat-ed Capsule Combined with Mesalamine in Treating Ulcerative Colitis

    Institute of Scientific and Technical Information of China (English)

    曹燕飞

    2011-01-01

    目的 比较单用美沙拉嗪与枯草杆菌二联活菌肠溶胶囊联合美沙拉嗪治疗溃疡性结肠炎的疗效,为临床治疗溃疡性结肠炎提供合理用药的依据.方法 将我院2005年1月-2009年5月人院的溃疡性结肠炎患者86例分为单用组和联合组各43例,分别接受单用美沙拉嗪与枯草杆菌二联活菌肠溶胶囊联合美沙拉嗪治疗的方法.治疗后对两组的治疗有效率、Suiherland疾病活动指数、肠镜分级、病理组织学分级变化等进行比较,评价其疗效和安全性.结果 两组治疗后的有效率、Sutherland疾病活动指数、肠镜分级、病理组织学分级变化比较均具有统计学意义(P<0.05).结论 枯草杆菌二联活菌肠溶胶囊联合美沙拉嗪治疗溃疡性结肠炎的疗效优于单用美沙拉嗪,且安全性高,值得临床推广应用.

  2. 美沙拉嗪颗粒联合美常安胶囊对溃疡性结肠炎患者临床疗效及炎症反应的影响%Effect of Mesalamine Combined with Medilac-S on Clinical Symptoms and Inflammatory Response in Patients with Ulcerative Colitis

    Institute of Scientific and Technical Information of China (English)

    梁勇; 颜丽萍; 苏林; 李弘; 闫玉栋

    2016-01-01

    目的:研究美沙拉嗪颗粒联合美常安胶囊治疗溃疡性结肠炎的临床疗效及对炎症反应的影响.方法:选取本院自2015年1月至2016年1月收治的92例轻、中度溃疡性结肠炎患者,随机分为对照组和治疗组各46例.对照组单独行美沙拉嗪颗粒治疗,治疗组行美沙拉嗪颗粒联合美常安胶囊治疗,总疗程16周.对比观察两组患者治疗后对临床症状、临床症状积分、有效率以及炎症指标的改变.结果:治疗组患者的症状改善情况、总有效率均显著高于对照组(P<0.05),治疗组术前术后临床症状评分也明显优于对照组(P<0.05);两组患者治疗后红细胞沉降率(ESR)和C-反应蛋白(CRP)均明显降低,且治疗组降低更显著,差异有统计学意义(P<0.05).结论:美沙拉嗪颗粒联合美常安胶囊可有效提高轻、中度溃疡性结肠炎治疗效果,减轻炎症反应,改善患者临床症状,临床效果显著,值得推广和应用.

  3. 美沙拉嗪和双歧杆菌三联活菌联用治疗显微镜下结肠炎疗效分析%Curative effect of Mesalamine and Bifidobacterium triple viable in treating microscopic colitis

    Institute of Scientific and Technical Information of China (English)

    魏莹; 郑兰; 陈华

    2015-01-01

    目的 探讨美沙拉嗪和双歧杆菌三联活菌联用治疗显微镜下结肠炎(microscopic colitis,MC)的疗效.方法 将确诊为MC的患者(85例)随机分为治疗组(43例)和对照组(42例).治疗组给予美沙拉嗪肠溶片和双歧杆菌三联活菌片,对照组单独给予美沙拉嗪肠溶片,疗程均为1个月,治疗前后均给予结肠镜检查.结果 治疗组总有效率90.7%,对照组总有效率71.4%,治疗组3个月复发率20.9%,6个月复发率34.9%;对照组3个月复发率47.6%,6个月复发率64.3%;治疗组疗效明显优于对照组,差异有统计学意义(P<0.05).结论 美沙拉嗪和双歧杆菌三联活菌联用治疗MC有确切疗效.

  4. Tetomilast.

    LENUS (Irish Health Repository)

    O'Mahony, Seamus

    2012-02-03

    Otsuka is developing a once-daily oral formulation of the phosphodiesterase-4 inhibitor tetomilast for the potential treatment of ulcerative colitis (phase III) and chronic obstructive pulmonary disease (phase II).

  5. 21 CFR 520.928 - Firocoxib tablets.

    Science.gov (United States)

    2010-04-01

    .... Administer once daily for osteoarthritis. Administer approximately 2 hours before soft-tissue or orthopedic...; and for the control of postoperative pain and inflammation associated with soft-tissue and orthopedic... veterinarian....

  6. Results of a randomized, double-blind, placebo-controlled study of mirabegron in a Taiwanese population with overactive bladder and comparison with other clinical trials

    Directory of Open Access Journals (Sweden)

    Hann-Chorng Kuo

    2015-03-01

    Conclusion: Mirabegron at a dose of 50 mg once daily for 12 weeks is superior to placebo in reducing the frequency of micturitions in Taiwanese patients with symptoms of OAB. No clinically relevant, serious adverse events were identified.

  7. Atazanavir pharmacokinetics, efficacy and safety in pregnancy: a systematic review

    NARCIS (Netherlands)

    Eley, T.; Bertz, R.; Hardy, H.; Burger, D.M.

    2013-01-01

    BACKGROUND: For some antiretroviral therapies, drug concentrations are reduced during pregnancy, potentially compromising effective virological suppression. METHODS: Data on atazanavir boosted with ritonavir in pregnancy are reviewed. RESULTS: With standard atazanavir/ritonavir 300/100 mg once-daily

  8. Dialysis-Associated Hypertension Treated with Telmisartan - DiaTel: A Pilot, Placebo-Controlled, Cross-Over, Randomized Trial: e79322

    National Research Council Canada - National Science Library

    Matthias Huber; Till Treutler; Peter Martus; Antje Kurzidim; Reinhold Kreutz; Joachim Beige

    2013-01-01

    .... We designed and conducted a randomised, placebo-controlled, double-blind and cross-over trial for treatment of dialysis-associated hypertension with telmisartan 80 mg once daily or placebo on top...

  9. Dialysis-associated hypertension treated with Telmisartan--DiaTel: a pilot, placebo-controlled, cross-over, randomized trial

    National Research Council Canada - National Science Library

    Huber, Matthias; Treutler, Till; Martus, Peter; Kurzidim, Antje; Kreutz, Reinhold; Beige, Joachim

    2013-01-01

    .... We designed and conducted a randomised, placebo-controlled, double-blind and cross-over trial for treatment of dialysis-associated hypertension with telmisartan 80 mg once daily or placebo on top...

  10. Bicalutamide 150 mg plus standard care vs standard care alone for early prostate cancer

    DEFF Research Database (Denmark)

    McLeod, David G; Iversen, Peter; See, William A;

    2006-01-01

    To evaluate, in the ongoing Early Prostate Cancer (EPC) trial programme, the efficacy and tolerability of bicalutamide 150 mg once daily in addition to standard care for localized or locally advanced, nonmetastatic prostate cancer....

  11. Meeting notes from the 3rd IAS Conference. Old drugs, new data.

    Science.gov (United States)

    Hicks, Charles B

    2005-10-01

    Researchers reported on the benefits of once-daily tenofovir + FTC + efavirenz as initial therapy, described a needle-free injection system for T-20, and announced the impending availability of lopinavir/ritonavir in tablet formulation.

  12. Eltrombopag for management of chronic immune thrombocytopenia (RAISE): a 6-month, randomised, phase 3 study

    DEFF Research Database (Denmark)

    Cheng, Gregory; Saleh, Mansoor N; Marcher, Claus

    2011-01-01

    Eltrombopag is an oral thrombopoietin receptor agonist for the treatment of thrombocytopenia. We aimed to compare the response to once daily eltrombopag versus placebo in patients with chronic immune thrombocytopenia during a 6-month period....

  13. Pharmacokinetic analysis to assess forgiveness of boosted saquinavir regimens for missed or late dosing

    Science.gov (United States)

    Dickinson, Laura; Boffito, Marta; Khoo, Saye H.; Schutz, Malte; Aarons, Leon J.; Pozniak, Anton L.; Back, David J.

    2013-01-01

    Objectives One potential concern of once-daily protease inhibitor administration is low trough concentrations and ultimately the ‘forgiveness’ or robustness in comparison with the originally licensed twice-daily dose. To give an estimation of ‘forgiveness’, we determined the length of time plasma drug concentrations were below target in HIV-infected patients receiving saquinavir/ritonavir regimens. Methods Seventy-seven pharmacokinetic profiles (saquinavir/ritonavir 1000/100 mg twice daily, n = 34; 1600/100 mg once daily, n = 26; 2000/100 mg once daily, n = 17) from five studies were combined, presented as twice- and once-daily percentiles (P10–P90) and compared. At percentiles where trough concentrations fell below the alleged minimum effective concentration (MEC; 100 ng/mL), the length of time below MEC was determined. Results Saquinavir concentrations were below MEC at P10 for 0.7 h for twice-daily saquinavir/ritonavir when compared with 8.6 and 6.6 h for 1600/100 and 2000/100 mg once daily, respectively. At P25, 1600/100 mg once daily produced suboptimal concentrations for 5.5 h in contrast to 0.5 h for 2000/100 mg once daily. Conclusions Here, we provide substantive data that indicate once-daily saquinavir, in particular 1600/100 mg, is not as robust as the twice-daily regimen based on a population of UK patients; this raises concern over late or missed doses. However, pharmacokinetic data can only ever be a guide to the impact on long-term efficacy. PMID:18467305

  14. Liraglutide in Type 2 Diabetes Mellitus: Clinical Pharmacokinetics and Pharmacodynamics

    OpenAIRE

    2015-01-01

    Liraglutide is an acylated glucagon-like peptide-1 analogue with 97 % amino acid homology with native glucagon-like peptide-1 and greatly protracted action. It is widely used for the treatment of type 2 diabetes mellitus, and administered by subcutaneous injection once daily. The pharmacokinetic properties of liraglutide enable 24-h exposure coverage, a requirement for 24-h glycaemic control with once-daily dosing. The mechanism of protraction relates to slowed release from the injection site...

  15. Medication adherence and persistence in the treatment of Canadian ulcerative colitis patients: analyses with the RAMQ database

    Directory of Open Access Journals (Sweden)

    Lachaine Jean

    2013-01-01

    Full Text Available Abstract Background Although high non-adherence to medication has been noticed for ulcerative colitis (UC, little is known about adherence to mesalamine treatments and determinants that can predict adherence. The objective of this study was to assess adherence and persistence to mesalamine treatments and their potential determinants in mild to moderate UC patients in a real-life setting in Quebec, Canada. Methods A retrospective prescription and medical claims analysis was conducted using a random sample of mesalamine users with UC. For inclusion, patients were required to initiate an oral mesalamine treatment between January 2005 and December 2009. Patients with a diagnosis of Crohn’s disease were excluded. Treatment adherence (medication possession ratio [MPR] and persistence were evaluated over a 1-year period after the index prescription using the Kaplan-Meier method with log-rank test and stepwise regression to identify potential determinants. Results A sample of 1,681 of the new oral mesalamine users (mean age = 55.3 patients was obtained. Overall, the percentage of patients with a MPR of 80% or greater at 12 months was 27.7%, while persistence was 45.5%. Among patients treated with mesalamine delayed/extended-release tablets (Mezavant®, adherence and persistence were 40.9% and 71.9%, respectively. Predictors of high adherence included, male gender (OR=1.3; 95% confidence interval [CI]=1.1–1.6, older age (>60 years; OR=1.6; 95% CI=1.3–2.0 and current use of corticosteroids (OR=1.4; 95% CI=1.1–1.8. Predictors of high persistence included male sex (OR=1.4; 95% CI=1.1–1.7, current use of corticosteroids (OR=1.4; 95% CI=1.1–1.7 and presence of hypertension or respiratory diseases (OR=1.2; 95% CI=1.01–1.55. Conclusions The majority of patients with UC exhibited low adherence and persistence to mesalamine treatments. Various determinants of improved adherence and persistence were identified.

  16. Synthetic Transformation on Shikimic Acid.

    Science.gov (United States)

    1988-03-15

    Hetero 25 Diels-Alder Reactions of an Azadiene 6 ORTEP Plot and MMX Conformation of 46 32 7 Diels-Alder Reactions of 72 43 8 Diagram of 75 from MMX...Route A would rely on the use of an azadiene in a Diels-Alder reaction similar to that demonstrated by Ghosez. 2 6 Here the shikimate nucleus would...a Diels-Alder addition using an azadiene analogous to that explored earlier by Ghosez. 2 8 . In this plan, the 1,2- double bond of shikimate serves

  17. Therapeutic effects of Clostridium butyricum on experimental colitis induced by oxazolone in rats

    Institute of Scientific and Technical Information of China (English)

    Hai-Qiang Zhang; Tomas T Ding; Jun-Sheng Zhao; Xin Yang; Hai-Xia Zhang; Juan-Juan Zhang; Yun-Long Cui

    2009-01-01

    AIM: To evaluate the therapeutic effects of a probiotic supplement ( Clostridium butyricum, CGMCC0313) in a chemically-induced rat model of experimental colitis. METHODS: An experimental ulcerative colitis model was established by rectal injection of oxazolone into the colon of 40 Wistar rats randomly divided into four groups. The positive control group was sacrificed 3 d after colitis onset. The remaining groups were fed daily with either 2 mL of C. butyricum (2.3 ?á 1011 CFU/L), 2 mL of mesalamine (100 g/L), or 1 mL of sodium butyrate (50 mmol/L) for 21 d. The animals?ˉ body weight, behavior, and bowel movements were recorded weekly. After sacrifice, visual and microscopic observations of pathological changes of colon tissue were made, body weight and wet colon mass index were measured and recorded, and serum levels of interleukin-23 (IL-23) and TNF-α were measured using ELISA. Expression of calcitonin gene-related peptide in colon tissue was measured by RT-PCR. Finally, changes in rat intestinal microflora status were measured in all groups. RESULTS: We found that treatment with C. butyricum lowered the serum levels of both IL-23 and tumor necrosis factor-α (TNF-α) with similar or even better efficiency than that of mesalamine or sodium butyrate. The rat intestinal flora appeared to recover more quickly in the group treated with C. butyricum than in the mesalamine and sodium butyrate groups. Finally, we found that the expression level of calcitonin gene related peptide was elevated in colon tissue in the sodium butyrate treated group but not in the C. butyricum or mesalamine treated groups, indicating a sensitization of colon following sodium butyrate treatment. CONCLUSION: In our experimental colitis model, treatment with C. butyricum CGMCC0313, a probiotic supplement, is at least as efficient as treatment with mesalamine.

  18. Phase 1b study of new posaconazole tablet for prevention of invasive fungal infections in high-risk patients with neutropenia.

    Science.gov (United States)

    Duarte, Rafael F; López-Jiménez, Javier; Cornely, Oliver A; Laverdiere, Michel; Helfgott, David; Haider, Shariq; Chandrasekar, Pranatharthi; Langston, Amelia; Perfect, John; Ma, Lei; van Iersel, Marlou L P S; Connelly, Nancy; Kartsonis, Nicholas; Waskin, Hetty

    2014-10-01

    Posaconazole tablets, a new oral formulation of posaconazole, can be effective when given as antifungal prophylaxis to neutropenic patients at high risk for invasive fungal infection (e.g., those with acute myelogenous leukemia or myelodysplastic syndrome). Such effectiveness might be specifically important to patients with poor oral intake because of nausea, vomiting, or chemotherapy-associated mucositis. This was a prospective, global study in high-risk patients to characterize the pharmacokinetics and safety profile of posaconazole tablets and to identify the dose of posaconazole tablets that would provide exposure within a predefined range of exposures (steady-state average concentration [area under the concentration-time curve/24 h] of ≥500 ng/ml and ≤2,500 ng/ml in >90% of patients). The study evaluated two sequential dosing cohorts: 200 mg posaconazole once daily (n = 20) and 300 mg posaconazole once daily (n = 34) (both cohorts had a twice-daily loading dose on day 1) taken without regard to food intake during the neutropenic period for ≤28 days. The exposure target was reached (day 8) in 15 of 19 (79%) pharmacokinetic-evaluable patients taking 200 mg posaconazole once daily and in 31 of 32 (97%) patients taking 300 mg posaconazole once daily; 300 mg posaconazole once daily achieved the desired exposure target. Posaconazole tablets were generally well tolerated in high-risk neutropenic patients. (This study has been registered at ClinicalTrials.gov under registration no. NCT01777763.).

  19. Long-acting β-adrenoceptor agonists in the management of COPD: focus on indacaterol

    Science.gov (United States)

    Beier, Jutta; Beeh, Kai M

    2011-01-01

    Bronchodilators are the cornerstone of severe chronic obstructive pulmonary disease (COPD) treatment to improve airflow, symptoms, exercise tolerance, and exacerbations. There is convincing evidence that regular treatment with long-acting bronchodilators is more effective and convenient than treatment with short-acting bronchodilators. Long-acting β-2-agonists include the twice-daily drugs formoterol and salmeterol and, more recently, once-daily indacaterol. Studies with head-to-head comparisons of long-acting bronchodilators are scant, but novel data from controlled trials with the once-daily β(2)-agonist indacaterol indicate superior bronchodilation and clinical efficacy of indacaterol at recommended doses over twice-daily long-acting β(2)-agonists, and at least equipotent bronchodilation compared with once-daily tiotropium. The recent therapeutic developments in COPD underscore a shift from short-acting bronchodilators with multiple dosings per day to reduced dosing frequency and prolonged duration of action, including once-daily treatment, with more consistent effects on various clinical outcomes. This review summarizes relevant clinical data for twice-daily β-2-agonists in COPD, and further focuses on novel data for once-daily indacaterol, including head-to-head comparison trials. PMID:21814459

  20. HPLC determination of calcium pantothenate and two preservatives in topical cream.

    Science.gov (United States)

    Havlíková, L; Matysová, L; Nováková, L; Solich, P

    2006-05-03

    A RP-HPLC method for simultaneous determination of calcium pantothenate and two preservatives methylparaben and propylparaben present in topical cream was developed. Different analytical columns with various stationary phases were tested. During method development, Supelco Discovery C18 column (125 mmx4.0 mm, 5 microm) and Zorbax SB-CN column (150 mmx4.6 mm, 5 microm) were tested. Both were not convenient for analytical separation because of the co-elution of calcium pantothenate with dead volume, and problems with the peak-shape of all components. Good separation was achieved using Zorbax TSM (250 mmx4.6 mm, 5 microm) and Hypersil ODS column (250 mmx4.6 mm, 5 microm), the latter was finally used for the analysis. The analysis time was 12 min, at flow rate 0.7 ml min-1. Chromatography was performed using binary mobile phase composed of methanol and phosphoric acid, pH 2.5, 65:35 (v/v). UV detection was accomplished at 214 nm. The method was validated according to ICH guideline recommendations. The method is suitable for practical routine analysis of commercially produced topical pharmaceutical preparations.

  1. Plasma biomarkers in the diagnosis of acute ischemic stroke.

    Science.gov (United States)

    Kim, Myeong Hee; Kang, So Young; Kim, Myung Chun; Lee, Woo In

    2010-01-01

    Rapid diagnosis and timely treatment improves the outcome in patients with ischemic stroke, but a rapid and sensitive blood test for ischemic stroke does not exist. This study tested whether a panel of biomarkers might be useful in the diagnosis of acute ischemic stroke. Consecutive patients with suspected stroke presenting to the emergency department of a university hospital in Korea were enrolled. Plasma specimens were assayed for brain natriuretic peptide, D-dimer, matrix metalloproteinase-9, S100β, and a proprietary composite multimarker index (MMX). There were 139 patients in this study, 89 of whom were diagnosed with acute ischemic stroke, 11 with acute cerebral hemorrhage, and 39 with other brain disorders. The MMX value was significantly higher in the patients with acute ischemic stroke in comparison to 57 healthy controls (p acute ischemic stroke vs those with acute cerebral hemorrhage (p = 0.884). The discriminatory capacity of MMX was modest, with an area under the receiver-operating-characteristic curve of 0.714 for acute stroke. Ischemic stroke was not diagnosed by any of the biochemical markers individually. Although the data suggest that MMX may be helpful to diagnose an acute stroke, it does not discriminate between acute ischemic stroke and acute hemorrhagic stroke.

  2. Sulfasalazine attenuates ACL transection and medial menisectomy-induced cartilage destruction by inhibition of cystine/glutamate antiporter.

    Science.gov (United States)

    Tsai, Wei-Yuan; Tsai, Ru-Yin; Liu, Chih-Chung; Wu, Jia-Lin; Wong, Chih-Shung

    2016-04-01

    We had previously demonstrated that excitatory amino acid glutamate plays a role in the progression and severity of knee osteoarthritis (OA), and early hyaluronic acid injection attenuates the OA progression by attenuation of knee joint glutamate level, which was also related to the cystine/glutamate antiporter system X (system XC-) expression. System XC- uptakes cystine into chondrocytes for glutathione (GSH) synthesis, but the role of system XC- in OA is rarely addressed. Sulfasalazine (SSZ) is a system XC- inhibitor; SSZ was applied intra-articularly to study the function of system XC- in the development of OA in rats subjected to anterior cruciate ligament transection and medial meniscectomy (ACLT + MMx). Moerover, the system XC- activator N-acetylcysteine (NAC) was also applied to verify the role of system XC-. The intra-articular injection of SSZ significantly attenuated knee swelling and cartilage destruction in the knees of ACLT + MMx rats and this effect was blocked by NAC. The results showed that inhibition of system XC- function can attenuate ACLT + MMx-induced cartilage destruction. In the present study, system XC- inhibitor SSZ was shown to reduce glutamate content in synovial fluid and GSH in chondrocytes. It was also showed SSZ could attenuate ACLT + MMx-induced cartilage destruction, and treatment of NAC reversed the protective effect of SSZ.

  3. Comparative efficacy of indacaterol in chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Ribeiro M

    2012-03-01

    Full Text Available Marcos Ribeiro, Kenneth R ChapmanAsthma and Airway Centre, University Health Network, Toronto Western Hospital, University of Toronto, Toronto, ON, CanadaAbstract: Long-acting bronchodilators have been shown to improve multiple clinical outcomes in chronic obstructive pulmonary disease (COPD including lung function, symptoms, dyspnea, quality of life, and exacerbations. Indacaterol is a novel, inhaled, long-acting β2-agonist providing 24-hour bronchodilation with once-daily dosing. It is currently approved for the maintenance treatment of COPD to be administered as 150 or 300 µg once-daily doses as licensed in many countries and 75 µg as licensed in the US by means of a single-dose dry powder inhaler. The data from clinical development support a favorable safety and tolerability profile within the β2-agonist drug class, with no relevant issues identified. Current evidence indicates that indacaterol is suitable for use as first-line monotherapy in COPD patients with moderate disease (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage II and beyond that do not require an inhaled corticosteroid (ICS as per GOLD guidelines, or in combination with an ICS in severe or very severe patients with repeated exacerbations. Data from trials with the novel once-daily β2-agonist, indacaterol, indicate superior bronchodilation and clinical efficacy over twice-daily long-acting β2-agonists and at least equipotent bronchodilation as once-daily tiotropium. Bronchodilators are central in the symptomatic management of COPD. It is likely that once-daily dosing of a bronchodilator would be a significant convenience and probably a compliance-enhancing advantage, leading to improved overall clinical outcomes in patients with COPD.Keywords: indacaterol, onset of action, chronic obstructive pulmonary disease, bronchodilators, once-daily, long-acting β2-agonists

  4. Potent, transient inhibition of BCR-ABL with dasatinib 100 mg daily achieves rapid and durable cytogenetic responses and high transformation-free survival rates in chronic phase chronic myeloid leukemia patients with resistance, suboptimal response or intolerance to imatinib

    Science.gov (United States)

    Shah, Neil P.; Kim, Dong-Wook; Kantarjian, Hagop; Rousselot, Philippe; Llacer, Pedro Enrique Dorlhiac; Enrico, Alicia; Vela-Ojeda, Jorge; Silver, Richard T.; Khoury, Hanna Jean; Müller, Martin C.; Lambert, Alexandre; Matloub, Yousif; Hochhaus, Andreas

    2010-01-01

    Background Dasatinib 100 mg once daily achieves intermittent BCR-ABL kinase inhibition and is approved for chronic-phase chronic myeloid leukemia patients resistant or intolerant to imatinib. To better assess durability of response to and tolerability of dasatinib, data from a 2-year minimum follow-up for a dose-optimization study in chronic-phase chronic myeloid leukemia are reported here. Design and Methods In a phase 3 study, 670 chronic-phase chronic myeloid leukemia patients with resistance, intolerance, or suboptimal response to imatinib were randomized to dasatinib 100 mg once-daily, 50 mg twice-daily, 140 mg once-daily, or 70 mg twice-daily. Results Data from a 2-year minimum follow-up demonstrate that dasatinib 100 mg once daily achieves major cytogenetic response and complete cytogenetic response rates comparable to those in the other treatment arms, and reduces the frequency of key side effects. Comparable 2-year progression-free survival and overall survival rates were observed (80% and 91%, respectively, for 100 mg once daily, and 75%–76% and 88%–94%, respectively, in other arms). Complete cytogenetic responses were achieved rapidly, typically by 6 months. In patients treated with dasatinib 100 mg once daily for 6 months without complete cytogenetic response, the likelihood of achieving such a response by 2 years was 50% for patients who had achieved a partial cytogenetic response, and only 8% or less for patients with minor, minimal, or no cytogenetic response. Less than 3% of patients suffered disease transformation to accelerated or blast phase. Conclusions Intermittent kinase inhibition can achieve rapid and durable responses, indistinguishable from those achieved with more continuous inhibition. PMID:20139391

  5. Comparison of Ertapenem and Ceftriaxone Therapy for Acute Pyelonephritis and Other Complicated Urinary Tract Infections in Korean Adults: A Randomized, Double-Blind, Multicenter Trial

    OpenAIRE

    PARK, DAE WON; Peck, Kyong Ran; Chung, Moon Hyun; Lee, Jin Seo; Park, Yoon Soo; Kim, Hyo Youl; Lee, Mi Suk; Kim, Jung Yeon; Yeom, Joon Sup; Kim, Min Ja

    2012-01-01

    The efficacy and safety of ertapenem, 1 g once daily, were compared with that of ceftriaxone, 2 g once daily, for the treatment of adults with acute pyelonephritis (APN) and complicated urinary tract infections (cUTIs) in a prospective, multicenter, double-blinded, randomized study. After ≥ 3 days of parenteral study therapy, patients could be switched to an oral agent. Of 271 patients who were initially stratified by APN (n = 210) or other cUTIs (n = 61), 66 (48.9%) in the ertapenem group an...

  6. Different effects of calcium antagonist and beta-blocker therapy on left-ventricular diastolic function in ischemic heart disease. A direct comparison of the impact of mibefradil and atenolol

    DEFF Research Database (Denmark)

    Hassager, C; Thygesen, K; Grande, P;

    2001-01-01

    OBJECTIVE: To compare the effect of a calcium antagonist and a beta-blocker on left-ventricular diastolic function in patients with ischemic heart disease. METHODS: 138 patients with chronic stable angina pectoris were randomized in a multicenter, double-blind trial to treatment with either...... mibefradil or atenolol for 6 weeks (50 mg once daily for 2 weeks followed by 100 mg once daily for 4 weeks). The ratio between early (E) and late (A) diastolic mitral flow velocities (E/A), the E wave deceleration time (DT) and the left ventricular isovolumetric relaxation time (IRT) were measured by Doppler...

  7. Efficacy of controlled-release isosorbide-5-mononitrate as adjunctive treatment to beta-blocking agents in patients with stable angina pectoris

    DEFF Research Database (Denmark)

    Svendsen, Jesper Hastrup; Aldershvile, J; Abildgaard, U

    1989-01-01

    to a beta blocker. In bicycle ergometer exercise tests performed 4 h after study drug intake, total exercise time and time until 1-mm ST-depression increased significantly during both regimens as compared with placebo (p less than 0.05). However, only the 60-mg once-daily regimen was significantly better...... than placebo with regard to time until angina pectoris. The results indicate that ISMN-CR 60 mg once daily is effective as adjunctive to beta-blocker treatment, and nitrate tolerance appeared to develop during the twice-daily regimen. In 10 of the patients, the effect of additional sublingual...

  8. ▼Olodaterol--another LABA for COPD.

    Science.gov (United States)

    2015-04-01

    ▼Olodaterol solution for inhalation (Striverdi Respimat-Boehringer Ingelheim) is a long-acting beta2 agonist (LABA) licensed for once-daily use as maintenance bronchodilator therapy for chronic obstructive pulmonary disease (COPD). This is the third LABA to be licensed in the UK for once-daily use for patients with COPD. DTB has previously reviewed the use of indacaterol and vilanterol in combination with fluticasone furoate (▼Relvar Ellipta).1,2 In this article we consider the evidence for olodaterol and whether it offers any advantages in the management of COPD.

  9. Anipamil prevents ST depression in patients with stable angina pectoris

    DEFF Research Database (Denmark)

    Larsen, C T; Sørum, C; Rasmussen, V

    1993-01-01

    . The patients received anipamil 80 mg once daily, anipamil 160 mg once daily, and placebo in a randomized order. At the end of each treatment period the patients underwent 24-hour ambulatory ECG recording. Nineteen patients were included, all with typical stable angina pectoris for at least 2 months, exercise...... test with > or = 0.10 mV horizontal or down-sloping ST-segment depression and limited by angina pectoris, and at least 10 attacks of angina pectoris in the initial single-blind placebo period. During the placebo period, a total duration of transient myocardial ischemia > or = 0.10 mV during the 24-hour...

  10. Keyboard cleanliness: a controlled study of the residual effect of chlorhexidine gluconate.

    Science.gov (United States)

    Jones, Rhiannon; Hutton, Anna; Mariyaselvam, Maryanne; Hodges, Emily; Wong, Katherine; Blunt, Mark; Young, Peter

    2015-03-01

    A controlled trial of once daily cleaning of computer keyboards in an intensive care unit was performed comparing 2% chlorhexidine gluconate-70% isopropyl alcohol (CHG) and a chlorine dioxide-based product used as a standard in our hospital. A study before and after the introduction of once daily keyboard cleaning with CHG in the wider hospital was also completed. Cleaning with CHG showed a sustained and significant reduction in bacterial colony forming units compared with the chlorine dioxide-based product, demonstrating its unique advantage of maintaining continuous keyboard cleanliness over time.

  11. Olmsted Syndrome

    Directory of Open Access Journals (Sweden)

    Sirka C

    1999-01-01

    Full Text Available A 20-year-old Sikh man had palmoplantar keratoderma, flexion deformity of digits, universal alopecia, keratotic plaques at the angles of mouth, gluteal cleft, knees and dorsal aspects of the metacarpophalangeal joints of the hand; features of Olmsted syndrome. He had normal nails, teeth, oral mucosa and normal joint movements. Treatment with acitretin, 25mg/day for three and a half months, followed by 25mg once daily alternating with 50mg once daily for 3 months resulted in significant improvement.

  12. Design, Development and Characterization of Extended Release Multiunit Particulate System of Anti-Inflammatory Drug

    Directory of Open Access Journals (Sweden)

    Dhiren Daslaniya

    2009-07-01

    Full Text Available Multi unit particulate system has long been employed to improve the bioavailability of drugs. Mesalamine pellets were prepared by Coating drug solution on sugar sphere followed by various functional coating. The influence of rate controlling membrane made up of Eudragit RSPO and Eudragit RLPO in combination with delay release polymer coating with Eudragit L100 in different proportions on drug release kinetics was studied. Pellets were for the various parameter like Physical characteristics, assay and in-vitro dissolution profile. The study confirmed that mesalamine can be delivered by multi unit particulate system into lower part of intestine. Optimized formulations were evaluated for In-vitro release profile. The optimized formula was stable at accelerated storage condition 40°C / 75 % RH. Prepared Pellets can be used in the treatment of the ulcerative colitis.

  13. Efficacy of early treatment with infliximab in pediatric Crohn’s disease

    Institute of Scientific and Technical Information of China (English)

    Jong; Seung; Lee; Jee; Hyun; Lee; Ji; Hyuk; Lee; Hye; Jin; Lee; Mi; Jin; Kim; Hae; Jeong; Lee; Yon; Ho; Choe

    2010-01-01

    AIM: To investigate the effectiveness of early infliximab use for induction and maintenance therapy in pediatric Crohn’s disease. METHODS: We performed a retrospective chart review of 36 patients with Crohn’s disease. Ten patients (group A) were treated with mesalamine after induction therapy with oral prednisolone, and 13 patients (group B) were treated with azathioprine after induction therapy with oral prednisolone. Thirteen patients (group C) received infliximab and azathioprine for induction and mainte...

  14. Microscopic Colitis: An Approach to Treatment

    Directory of Open Access Journals (Sweden)

    Nilesh Chande

    2008-01-01

    Full Text Available Microscopic colitis – including collagenous colitis and lymphocytic colitis – causes chronic watery diarrhea, usually in middle-aged or elderly patients. There is an association with celiac disease and certain medications. Medical treatment includes various antidiarrheal agents, mesalamine, corticosteroids and immunosuppressant drugs. Rarely, patients require surgery for refractory disease. An evidence-based and practical approach to treatment should optimize the treatment response while minimizing potential adverse events.

  15. Interstitial Nephritis in a Patient with Inflammatory Bowel Disease

    Directory of Open Access Journals (Sweden)

    Payaswini Vasanth

    2016-01-01

    Full Text Available Tubulointerstitial nephritis in patients with inflammatory bowel disease has been linked to the use of 5-ASA derivatives. Various aspects of this theory have been challenged with a potential role for the underlying autoimmune disorder. Steroids are the mainstay of treatment and mycophenolate mofetil might be an effective alternative. We report a patient who responded well to mycophenolate despite continuing mesalamine, the suspected offending agent.

  16. Interstitial Nephritis in a Patient with Inflammatory Bowel Disease

    Science.gov (United States)

    Vasanth, Payaswini; Parmley, Michelle; Torrealba, Jose

    2016-01-01

    Tubulointerstitial nephritis in patients with inflammatory bowel disease has been linked to the use of 5-ASA derivatives. Various aspects of this theory have been challenged with a potential role for the underlying autoimmune disorder. Steroids are the mainstay of treatment and mycophenolate mofetil might be an effective alternative. We report a patient who responded well to mycophenolate despite continuing mesalamine, the suspected offending agent. PMID:27703822

  17. Mesalazina: profilo farmacologico, terapeutico e farmacoeconomico

    Directory of Open Access Journals (Sweden)

    Mario Eandi

    2003-12-01

    Full Text Available The term inflammatory bowel diseases (IBD refers to two distinct clinical entities: Crohn.s disease and ulcerative cholitis, two chronic and non-specific disorders of unknown origin. Although quite uncommon and usually not life-threatening, IBDs have a strong economical impact, as they tend to affect patients in high productivity ages and require long and demanding therapies, medical and sometimes surgical. The pharmacological approaches to IBD treatment include aminosalicylates, corticosteroids and immunosuppressive agents. Aminosalicylic acids are the most widely used agents for maintaining remission and for the cure of mild-tomoderate forms of IBDs. This paper outlines the main pharmacological and clinical properties of one of these drugs, mesalamine (mesalazine. Mesalamine is the active moiety of sulfasalazine, an effective but not always tolerated agent. Mesalamine is available in several pharmaceutical forms, to be administered either by the oral or by the rectal route. As the therapeutic action of aminosalicylates is ascribed to their topical action on the inflamed intestine, while the adverse effects are believed to be caused by the systemically adsorbed (mainly in the first tract of the small bowel fraction, slow-release formulations are usually preferred. From an economical point of view, mesalamine appears to have a moderate acquisition cost, widely offset by the savings induced on direct sanitary and, most importantly, indirect costs of IBDs. In particular, the availability of a generic drug with advanced colon-delivery technology provides the physician with the opportunity to treat patients with the best available technology at a reasonable price.

  18. Exploiting the synergistic effect of chitosan-EDTA conjugate with MSA for the early recovery from colitis.

    Science.gov (United States)

    Singh, Kuldeep; Suri, Rajat; Tiwary, A K; Rana, Vikas

    2013-03-01

    The present study was aimed to exploit the antibacterial/antifungal and film coating potential of Chitosan-EDTA (CH-EDTA) conjugate in combination with mesalamine (anti-inflammatory agent) for the early recovery from TNBS induced coilitis. The results suggested CH:EDTA (1:1) spray coated mesalamine tablets has an ability to transport drug in buffer pH 6.8 with rat caecal content condition. The CH-EDTA shows high level of adhesiveness of coat with core tablet. Further, FTIR, DSC and SEM analysis suggested spray coating of CH-EDTA on tablets was beneficial as compared to ladling method as it enhances interaction density and showed resistance from pH (1.2, 6.8 and 7.4). The pharmacokinetic parameters, AUC and AUMC of spray coated tablets were respectively, 4.70 fold and 2.10 fold increased. A synergistic therapeutic effect with CH-EDTA spray coated mesalamine was observed as evaluated by colon/body weight ratio, clinical activity score and damage score. X ray image study supported that CH-EDTA conjugate successfully delivered MSA tablets to large intestine. Histopathology of colon tissues showed rapid recovery from TNBS induced colitis in rats within 4 days. The findings revealed decreased recovery period was due to combined effect of both CH-EDTA and MSA to treat TNBS induced colitis.

  19. Ultrasound-mediated gastrointestinal drug delivery.

    Science.gov (United States)

    Schoellhammer, Carl M; Schroeder, Avi; Maa, Ruby; Lauwers, Gregory Yves; Swiston, Albert; Zervas, Michael; Barman, Ross; DiCiccio, Angela M; Brugge, William R; Anderson, Daniel G; Blankschtein, Daniel; Langer, Robert; Traverso, Giovanni

    2015-10-21

    There is a significant clinical need for rapid and efficient delivery of drugs directly to the site of diseased tissues for the treatment of gastrointestinal (GI) pathologies, in particular, Crohn's and ulcerative colitis. However, complex therapeutic molecules cannot easily be delivered through the GI tract because of physiologic and structural barriers. We report the use of ultrasound as a modality for enhanced drug delivery to the GI tract, with an emphasis on rectal delivery. Ultrasound increased the absorption of model therapeutics inulin, hydrocortisone, and mesalamine two- to tenfold in ex vivo tissue, depending on location in the GI tract. In pigs, ultrasound induced transient cavitation with negligible heating, leading to an order of magnitude enhancement in the delivery of mesalamine, as well as successful systemic delivery of a macromolecule, insulin, with the expected hypoglycemic response. In a rodent model of chemically induced acute colitis, the addition of ultrasound to a daily mesalamine enema (compared to enema alone) resulted in superior clinical and histological scores of disease activity. In both animal models, ultrasound treatment was well tolerated and resulted in minimal tissue disruption, and in mice, there was no significant effect on histology, fecal score, or tissue inflammatory cytokine levels. The use of ultrasound to enhance GI drug delivery is safe in animals and could augment the efficacy of GI therapies and broaden the scope of agents that could be delivered locally and systemically through the GI tract for chronic conditions such as inflammatory bowel disease.

  20. Clearance of yellow pigments lutein and zeathanxin in channel catfish reared at different water temperatures

    Science.gov (United States)

    A study was conducted to determine clearance time of yellow pigments lutein and zeaxanthin in channel catfish at various temperatures. Fish of initial weight of 13.4 g were stocked into flow-through aquaria and fed once daily with a yellow pigment enhanced diet for 11 weeks when the yellow color be...

  1. The effects of prenatal exposure to atrazine on pubertal and postnatal reproductive indices in the female rat

    Science.gov (United States)

    Atrazine (ATR) is a commonly used herbicide that can exert negative reproductive effects in animals. We examined the effects of vehicle or ATR at 1, 5, 20 and 100 mg/kg/d, administered to Sprague-Dawley rats on gestational days 14-21, once daily or divided into two doses per day,...

  2. Safety and tolerability of montelukast in placebo-controlled pediatric studies and their open-label extensions

    DEFF Research Database (Denmark)

    Bisgaard, H.; Skoner, D.; Boza, M.L.;

    2009-01-01

    Montelukast is a potent leukotriene-receptor antagonist administered once daily that provides clinical benefit in the treatment of asthma and allergic rhinitis in children and adults. Because of its wide use as a pediatric controller, there is a need for a further review of the safety...

  3. Pharmacokinetics and acceptability of once- versus twice-daily lamivudine and abacavir in HIV type-1-infected Ugandan children in the ARROW Trial.

    NARCIS (Netherlands)

    Musiime, V.; Kendall, L.; Bakeera-Kitaka, S.; Snowden, W.B.; Odongo, F.; Thomason, M.; Musoke, P.; Adkison, K.; Burger, D.M.; Mugyenyi, P.; Kekitiinwa, A.; Gibb, D.M.; Walker, A.S.

    2010-01-01

    BACKGROUND: No data on once-daily dosing of nucleoside analogues in African children currently exist. We compared the pharmacokinetics (PK) of once- versus twice-daily lamivudine and abacavir treatment using the World Health Organization recommended weight band dosing of scored adult tablets. METHOD

  4. Phase I/II Clinical Study of Tosedostat, an Inhibitor of Aminopeptidases, in Patients With Acute Myeloid Leukemia and Myelodysplasia

    NARCIS (Netherlands)

    Lowenberg, Bob; Morgan, Gareth; Ossenkoppele, Gert J.; Burnett, Alan K.; Zachee, Pierre; Duehrsen, Ulrich; Dierickx, Daan; Mueller-Tidow, Carsten; Sonneveld, Pieter; Krug, Utz; Bone, Elisabeth; Flores, Nicolas; Richardson, Alison F.; Hooftman, Leon; Jenkins, Chris; Zweegman, Sonja; Davies, Faith

    2010-01-01

    Purpose To identify the maximum-tolerated dose (MTD) and to evaluate the antileukemic activity of tosedostat (formerly CHR-2797), an orally bioavailable aminopeptidase inhibitor. Patients and Methods In phase I, the MTD of once daily oral doses of tosedostat in hematologic malignancies was defined.

  5. 21 CFR 522.820 - Erythromycin.

    Science.gov (United States)

    2010-04-01

    ...) Indications for use. For the treatment of bacterial pneumonia, upper respiratory infections (tonsillitis... for use. For the treatment of bacterial pneumonia, upper respiratory infections (rhinitis, bronchitis... injection once daily for up to 5 days. (ii) Indications for use. For the treatment of bovine respiratory...

  6. One-year cost-effectiveness of tiotropium versus ipratropium to treat chronic obstructive pulmonary disease

    NARCIS (Netherlands)

    J.B. Oostenbrink (Jan); M.J. Al (Maiwenn); J.A. van Noord; W. Vincken; M.P.M.H. Rutten-van Mölken (Maureen)

    2004-01-01

    textabstractThe aim of this paper is to assess the health economic consequences of substituting ipratropium with the new, once-daily bronchodilator tiotropium in patients with a diagnosis of chronic obstructive pulmonary disease (COPD). This prospective cost-effectiveness analysis

  7. Teriflunomide for multiple sclerosis in real-world setting

    DEFF Research Database (Denmark)

    Elkjær, Maria Louise; Molnar, T; Illes, Z

    2017-01-01

    OBJECTIVES: Teriflunomide 14 mg is a once-daily oral disease-modifying treatment for relapsing-remitting multiple sclerosis. We examined adverse event (AE) profile and efficacy in real life. MATERIALS AND METHODS: In this observational cohort study, we retrospectively examined 1521 blood samples...

  8. Potentiation of Prostate Cancer Radiotherapy Using Antiangiogenic and Antitumor Therapies

    Science.gov (United States)

    2007-10-01

    University of Rochester Rochester, NY 14642 REPORT DATE: October 2007 TYPE OF REPORT: Final PREPARED FOR: U.S. Army Medical...Research and given once daily by gavage in a volume of 0.13 mL. Control animals received 0.5% carboxymethylcellulose drug carrier. Irradiations were

  9. Hypoglycaemia

    Institute of Scientific and Technical Information of China (English)

    Piya Sen Gupta; Andrea N Green; Tahseen A Chowdhury

    2011-01-01

    @@ A 58 year old white man who has had type 2 diabetes for 10 years is concerned about increasingly frequent hypoglycaemic episodes, usually in the late afternoon.He has been taking a stable, once daily dose of basal insulin glargine 14 units for two years, as well as twice daily gliclazide 160 mg and metformin 1000 mg.

  10. Effects of mometasone, fluticasone, and montelukast on bone mineral density in adults with asthma

    DEFF Research Database (Denmark)

    Maspero, Jorge; Backer, Vibeke; Yao, Ruji;

    2014-01-01

    asthma. METHODS: Adults with mild-moderate persistent asthma who did not receive ICS for ≥3 months were randomized to MF 400 μg once daily (QD) in the evening (pm), MF 200 μg QD pm, montelukast sodium (ML) 10 mg QD pm, or fluticasone propionate (FP) 250 μg twice daily. Included patients had 25-hydroxy...

  11. Dose-remission of pulsating electromagnetic fields as augmentation in therapy-resistant depression

    DEFF Research Database (Denmark)

    Straasø, Birgit; Lauritzen, Lise; Lunde, Marianne

    2014-01-01

    OBJECTIVE: To evaluate to what extent a twice daily dose of Transcranial Pulsating ElectroMagnetic Fields (T-PEMF) was superior to once daily in patients with treatment-resistant depression as to obtaining symptom remission after 8 weeks of augmentation therapy. METHODS: A self-treatment set...

  12. Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia

    DEFF Research Database (Denmark)

    Llibre, Josep M; Bravo, Isabel; Ornelas, Arelly

    2015-01-01

    BACKGROUND: Switching subjects with persistently undetectable HIV-1 viremia under antiretroviral treatment (ART) to once-daily tenofovir/emtricitabine (or lamivudine) + nevirapine is a cost-effective and well-tolerated strategy. However, the effectiveness of this approach has not been established...

  13. Rapid response of Trichophyton tonsurans-induced onychomycosis after treatment with terbinafine.

    Science.gov (United States)

    Aly, Raza; Hafeez, Zeba Hasan; Rodwell, Carmen; Frieden, Ilona J; Abrams, Beatrice

    2002-06-01

    We describe an 8-year-old Hispanic female who presented with distal subungual onychomycosis and tinea capitis. Both foci of infection yielded Trichophyton tonsurans upon culture, and were clinically and mycologically cured with terbinafine 125 mg, once daily for 1 week [DOSAGE ERROR CORRECTED]. This aspect of treatment with terbinafine has not previously been reported.

  14. Effect of montelukast on excessive airway narrowing response to methacholine in adult asthmatic patients not on controller therapy

    DEFF Research Database (Denmark)

    Ulrik, Charlotte Suppli; Diamant, Zuzana

    2009-01-01

    2-agonists p.r.n. only with a twice-documented absence of dose-response plateau, participated in a double-blind, parallel study with Mont (10 mg) or placebo once daily for 12 weeks. Mtc dose-response curves (0.03-256 mumol or >40% FEV(1) decline) were repeated every 4 weeks. The primary objective...

  15. Darifenacin for the treatment of overactive bladder

    NARCIS (Netherlands)

    B.F.M. Blok (Bertil); T. Corcos

    2007-01-01

    textabstractDarifenacin hydrobromide is a muscarinic receptor antagonist for once-daily treatment of overactive bladder (urinary urgency with or without urge incontinence, which may be associated with increased frequency of voiding and nocturia). Consistent with its high affinity for muscarinic M3

  16. Plasma pharmacokinetics of once- versus twice-daily lamivudine and abacavir: simplification of combination treatment in HIV-1-infected children (PENTA-13).

    NARCIS (Netherlands)

    Bergshoeff, A.S.; Burger, D.M.; Verweij, C.; Farrelly, L.; Flynn, J.; Prevost, M. Le; Walker, S.; Novelli, V.; Lyall, H.; Khoo, S.; Gibb, D.

    2005-01-01

    BACKGROUND: There are few data on plasma and intracellular pharmacokinetics (PK) of once-daily (q24h) nucleoside analogues in HIV-infected children. METHODS: Children aged 2-13 years receiving combination treatment containing lamivudine (3TC) (4 mg/kg) and/or abacavir (ABC) (8 mg/kg) twice daily (q1

  17. 21 CFR 520.903e - Febantel tablets.

    Science.gov (United States)

    2010-04-01

    ... kittens or 163.3 milligrams of febantel for use in dogs, puppies, and cats. (b) Sponsor. See 000859 in... kilogram body weight. Administer once daily for 3 consecutive days. (ii) Puppies and kittens fewer than 6...) For removal of hookworms (Ancylostoma tubaeforme) and ascarids (Toxocara cati) in cats and kittens....

  18. Significant one week efficacy of a calcipotriol plus betamethasone dipropionate scalp formulation

    DEFF Research Database (Denmark)

    Jemec, G.B.E.; Van De Kerkhof, P.C.M.; Enevold, A.;

    2011-01-01

    of the two-compound scalp formulation after 1 week of treatment. Methods Pooled data from two large pivotal phase III trials with 2920 patients receiving once-daily treatment for up to 8 weeks with either the two-compound scalp formulation (n = 1108), betamethasone dipropionate (n = 1118), calcipotriol (n...

  19. Comparative evaluation of fluoride release from PRG-composites and compomer on application of topical fluoride: An in-vitro study

    Directory of Open Access Journals (Sweden)

    Dhull K

    2009-03-01

    Full Text Available Aims and Objective: To determine the fluoride release from Giomer and Compomer, using different topical fluoride regimes, and to compare the amount of fluoride release from giomer with that of compomer. Materials and Method: Forty-eight specimens of each giomer and compomer were divided into four treatment groups, namely, control group, fluoridated dentifrice (500 ppm once daily group, fluoridated dentifrice (500 ppm twice daily group, fluoridated dentifrice (500 ppm once daily + fluoridated mouthwash (225 ppm group. Each specimen was suspended in demineralizing solution for six hours and remineralizing solution for 18 hours. Fluoride release was measured in both the demineralizing solution and remineralizing solution daily for seven days. Total daily fluoride release for each specimen was calculated by adding the amount released in the demineralizing solution to that released in remineralizing solution. Results and Conclusion: The fluoride release (ppm was found to be more in Giomer when compared to Compomer. The fluoride released from Giomer and Compomer was significantly greater in the acidic demineralizing solution than in the neutral remineralizing solution. It was found that increasing fluoride exposure significantly increased fluoride release from the giomer and compomer. It was found that the fluoride release from the subgroups of giomer and compomer was in the following order: fluoridated dentifrice twice daily > fluoridated dentifrice once daily + fluoridated mouthwash > fluoridated dentifrice once daily > control group. It was found that the giomer showed a greater fluoride uptake than the compomer.

  20. Reducing supplementation frequency for Nellore beef steers grazing tropical pastures

    Directory of Open Access Journals (Sweden)

    Roberta Carrilho Canesin

    2014-04-01

    Full Text Available Reduced supplementation frequency is a broadly applied management practice. Ruminants consuming low quality forages/pastures, supplemented less than once daily are able to maintain body weight gain (BWG, efficiency of use of dry matter, nitrogen and other nutrients, as compared with animals supplemented once daily. We evaluated the feeding behavior, dry matter intake (DMI, dry matter and organic matter digestibility (DMD and OMD, BWG, Longissimus muscle area and backfat depth of Nellore steers raised on Brachiaria brizantha cv. Marandu pastures during the dry season, with different supplementation patterns. Thirty six animals (338 ± 40.7 kg were distributed over nine paddocks according to a completely randomized design. Treatments were based on supplementation frequency: once daily (OD, once daily except Saturdays and Sundays (SS, or on alternate days (AD, at 1.0 %, 1.4 % and 2.0 % BW, respectively. Average total DMI accounted for 1.6 % BW day-1, with no effect of supplementation frequency. Supplementation frequency had no effect on BWG or grazing time during the day. There was no difference in Longissimus muscle area animals supplemented daily, SS and AD. The backfat depth was thinner in animals supplemented AD, but even in this case, it was within the standards considered satisfactory for a finishing steer. Reducing supplementation frequency seems a good option to lower labor costs without affecting feed efficiency or carcass quality in beef cattle grazing tropical pastures.

  1. Update of monotherapy trials with the new anti-androgen, Casodex (ICI 176,334). International Casodex Investigators

    DEFF Research Database (Denmark)

    Iversen, P

    1994-01-01

    Casodex (ICI 176,334) is a non-steroidal anti-androgen, which has a half-life compatible with once-daily oral dosing. In an open, phase II study on 267 patients given Casodex, 50 mg/day, an overall objective response (i.e. partial regression) was seen in 55.5% of patients (146 of 263) with a furt...

  2. Randomised study of Casodex 50 MG monotherapy vs orchidectomy in the treatment of metastatic prostate cancer. The Scandinavian Casodex Cooperative Group

    DEFF Research Database (Denmark)

    Iversen, P; Tveter, K; Varenhorst, E

    1996-01-01

    The effect of Casodex (ICI 176,334), a new, once-daily, selective antiandrogen, given as 50 mg monotherapy, was compared with orchidectomy in a randomised, multicentre, open study in 376 patients with metastatic prostate cancer. At 3 months, PSA was reduced by 86% in the Casodex group and by 96% ...

  3. Penile vibratory stimulation in the recovery of urinary continence and erectile function after nerve-sparing radical prostatectomy

    DEFF Research Database (Denmark)

    Fode, Mikkel; Borre, Michael; Ohl, Dana A

    2013-01-01

    were instructed in using a PVS device (FERTI CARE(®) vibrator). Stimulation was performed at the frenulum once daily by the patients in their own homes for at least 1 week before surgery. After catheter removal, daily PVS was re-initiated for a period of 6 weeks. Participants were evaluated at 3, 6...

  4. Anagrelide treatment in 52 patients with chronic myeloproliferative diseases

    DEFF Research Database (Denmark)

    Penninga, E; Jensen, B A; Hansen, P B

    2004-01-01

    In this retrospective multi-centre study, we report our experience with anagrelide in the treatment of thrombocytosis in patients with chronic myeloproliferative diseases. Our study included 52 patients (age 20-78 years). The initial anagrelide dose was, in general, 0.5 mg once daily and mean...

  5. The impact of treatment with indacaterol in patients with COPD : A post-hoc analysis according to GOLD 2011 categories A to D

    NARCIS (Netherlands)

    Kerstjens, Huib A. M.; Deslee, Gaetan; Dahl, Ronald; Donohue, James F.; Young, David; Lawrence, David; Kornmann, Oliver

    Background: Indacaterol is an inhaled, once-daily, ultra-long-acting beta(2)-agonist for the treatment of chronic obstructive pulmonary disease (COPD). We report on the effectiveness of indacaterol and other bronchodilators compared with placebo in patients across the Global Initiative for Chronic

  6. Open comparative trial of formestane versus megestrol acetate in postmenopausal patients with advanced breast cancer previously treated with tamoxifen

    NARCIS (Netherlands)

    Freue, M; Kjaer, M; Boni, C; Joliver, J; Janicke, F; Willemse, PHB; Coombes, RC; Van Belle, S; Perez-Carrion, R; Zieschang, J; de Palacios, PI; Rose, C

    2000-01-01

    The aim of the trial was to compare efficacy and safety of the aromatase inhibitor formestane (250 mg i.m. given every 2 weeks) with the progestin megestrol acetate (160 mg administered orally once daily), as second-line therapy in postmenopausal patients with advanced breast cancer previously treat

  7. Effect of low-concentration daily topical fluoride application on fluoride release of giomer and compomer: An in vitro study

    Directory of Open Access Journals (Sweden)

    K S Dhull

    2011-01-01

    Full Text Available Aims and Objective: To determine the effect of low-concentration daily topical fluoride application on fluoride release of Giomer and Compomer and to compare the amount of fluoride release from Giomer to that of Compomer. Materials and Methods: Forty-eight specimens of each Giomer and Compomer were divided into four treatment groups, namely, control group, fluoridated dentifrice (500 ppm once-daily group, fluoridated dentifrice (500 ppm twice-daily group and fluoridated dentifrice (500 ppm once-daily + fluoridated mouthwash (225 ppm group. Each specimen was suspended in demineralising solution for 6 h and remineralising solution for 18 h. Fluoride release was measured in both the demineralising solution and the remineralising solution daily for 21 days. Total daily fluoride release for each specimen was calculated by adding the amount released in the demineralising solution to that released in the remineralising solution. Results and Conclusion: The fluoride release (ppm was found to be higher in Giomer when compared with Compomer. The fluoride released from Giomer and Compomer was significantly higher in the acidic demineralising solution than in the neutral remineralising solution. It was found that increasing fluoride exposure significantly increased fluoride release from Giomer and Compomer. It was found that the fluoride release from the subgroups of Giomer and Compomer was in the following order: fluoridated dentifrice twice-daily > fluoridated dentifrice once-daily + fluoridated mouthwash > fluoridated dentifrice once-daily > control group. It was found that Giomer showed a greater fluoride uptake Compomer.

  8. Oral fingolimod (FTY720) in multiple sclerosis: two-year results of a phase II extension study

    DEFF Research Database (Denmark)

    O'Connor, P; Comi, G; Montalban, X;

    2009-01-01

    OBJECTIVE: To report the results of a 24-month extension of a phase II trial assessing the efficacy, safety, and tolerability of the once-daily oral sphingosine-1-phosphate receptor modulator, fingolimod (FTY720), in relapsing multiple sclerosis (MS). METHODS: In the randomized, double-blind, pla...

  9. Extended-Interval Aminoglycoside Use in Cystic Fibrosis Exacerbation in Children and Young Adults

    Science.gov (United States)

    Safi, Khalid H.; Damiani, Justina M.; Sturza, Julie; Nasr, Samya Z.

    2016-01-01

    This is a prospective quality improvement project for patients with cystic fibrosis who are 5 years of age and older who were admitted for intravenous antibiotic administration as part of treatment of cystic fibrosis exacerbation. The goal of this project was to compare the pharmacokinetics of once-daily versus thrice-daily aminoglycoside use when treating cystic fibrosis exacerbation in different age groups. Of the total of 119 patient encounters, 82.4% were started on once-daily dosing, and the remainder were started on thrice-daily dosing. Patients with pharmacokinetics allowing the continuation of once-daily dosing differed from patients who required a switch to thrice-daily dosing in terms of baseline forced expiratory volume in 1 second, forced expiratory flow from 25% to 75% of vital capacity, age, and body mass index (BMI) but were similar in BMI percentiles. The once-daily dosing group had higher mean 18-hour level, higher mean half-life, higher mean area under the curve, and lower mean elimination constant. This study showed that aminoglycoside clearance is higher in younger children. PMID:27336007

  10. The efficacy and safety of enoxaparin versus unfractionated heparin for prevention of deep vein thrombosis in elective cancer surgery. A double blind randomized multicentre trail with venographic assesment

    DEFF Research Database (Denmark)

    Bergkvist, A; Eldor, A; Thorlacius-Ussing, O.

    1997-01-01

    BACKGROUND: Surgery for malignant disease carries a high risk of deep vein thrombosis. The aim of this study was to evaluate the prophylactic effect of a low molecular weight heparin, enoxaparin, 40 mg once daily, beginning 2 h before surgery, compared with that of unfractionated low-dose heparin...

  11. Long-acting methylphenidate-OROS in youths with attention-deficit hyperactivity disorder suboptimally controlled with immediate-release methylphenidate : a study of cost effectiveness in The Netherlands

    NARCIS (Netherlands)

    Faber, Adrianne; van Agthoven, Michel; Kalverdijk, Luuk J; Tobi, Hiltje; de Jong-van den Berg, Lolkje T W; Annemans, Lieven; Postma, Maarten J

    2008-01-01

    Background: Attention-deficit hyperactivity disorder (ADHD) is the most common mental health disorder in youths. Stimulants are the drugs of first choice in the treatment of ADHD. It has been suggested that full costs associated with the treatment of ADHD may be reduced by once-daily administration

  12. Recurrent Cardiovascular Events Despite Antiplatelet Therapy in a Patient with Polycythemia Vera and Accelerated Platelet Turnover

    DEFF Research Database (Denmark)

    Pedersen, Oliver Heidmann; Larsen, Mads Lamm; Kristensen, Steen Dalby

    2017-01-01

    who suffered 6 episodes of cerebral infarctions and 1 myocardial infarction, despite treatment with clopidogrel. Following his last ischemic event, the antiplatelet therapy was intensified from initially clopidogrel monotherapy to dual antiplatelet therapy with aspirin 75 mg once daily and ticagrelor...

  13. A practical thrice weekly ertapenem dosage regime for chronic hemodialysis patients

    NARCIS (Netherlands)

    Bosma, M.; De Man, P.; Rietveld, A.; Touw, D.; Geerlings, C.

    2013-01-01

    Background: Ertapenem is a parenteral carbapenem. In patients undergoing hemodialysis a dosage reduction of 50%, as a dose of 0.5 gram once daily, is advised. Hospital admission or specialised home care is needed to administer ertapenem. As these patients are already visiting the hospital 3 times a

  14. Additional lunchtime basal insulin during insulin lispro intensive therapy in a randomized, multicenter, crossover study in adults - A real-life design

    NARCIS (Netherlands)

    Stades, AME; Hoekstra, JBL; van den Tweel, [No Value; Erkelens, DW; Holleman, F

    2002-01-01

    OBJECTIVE - This study vas performed to evaluate whether an additional dose of NPH insulin at lunchtime might overcome the deleterious effects of waning basal insulinemia on pre-dinner and evening glucose values during insulin lispro intensive therapy with once daily basal insulin at night, RESEARCH

  15. The tyrosine kinase inhibitor sunitinib affects ovulation but not ovarian reserve in mouse: A preclinical study

    NARCIS (Netherlands)

    V. Bernard (Valérie); J. Bouilly (Justine); P. Kramer (Piet); N. Carré (Nadège); M. Schlumberger (Martin); J.A. Visser (Jenny A.); J. Young (Jacques); N.B. Binart (Nadine Binart)

    2016-01-01

    textabstractThe aim of the study was to evaluate ovarian toxicity of tyrosine kinase inhibitor (TKI) sunitinib, since only scarce data are available on gonadal function after this treatment. Six-weekold female mice received orally, once daily, vehicle or sunitinib (50 mg/kg/d) during 5 weeks.

  16. Everolimus pharmacokinetics and its exposure-toxicity relationship in patients with thyroid cancer

    NARCIS (Netherlands)

    Wit, D. de; Schneider, T.C.; Moes, D.J.; Roozen, C.F.; Hartigh, J. den; Gelderblom, H.; Guchelaar, H.J.; Hoeven, J.J.M. van der; Links, T.P.; Kapiteijn, E.; Erp, N. van

    2016-01-01

    BACKGROUND: Everolimus is a mTOR inhibitor used for the treatment of different solid malignancies. Many patients treated with the registered fixed 10 mg dose once daily are in need of dose interruptions, reductions or treatment discontinuation due to severe adverse events. This study determined the

  17. Growth comparison of Nile tilapia (Oreochromis niloticus) and Blue ...

    African Journals Online (AJOL)

    Administrator

    2011-09-26

    Sep 26, 2011 ... the effect of interspecific hybridization and genetically modified breeding by introducing a fragmented .... de-chlorinated water and adequate aeration system, cleaned once daily by .... characteristics of both species, being more cold tolerant .... breeding: production of highly immune genetically modified Nile.

  18. Nifedipine gastrointestinal therapeutic system versus atenolol in stable angina pectoris

    NARCIS (Netherlands)

    deVries, RJM; vandenHeuvel, AFM; Lok, DJA; Claessens, RJJ; Bernink, PJLM; Pasteuning, WH; Kingma, JH; Dunselman, PHJM

    1996-01-01

    The gastrointestinal therapeutic system formulation of nifedipine enables a once-daily dosing resulting in predictable, relatively constant plasma concentrations. To evaluate the efficacy and safety of this formulation and to compare this with the beta-blocker atenolol, we conducted a double-blind,

  19. Safety and efficacy of an 8-week regimen of grazoprevir plus ruzasvir plus uprifosbuvir compared with grazoprevir plus elbasvir plus uprifosbuvir in participants without cirrhosis infected with hepatitis C virus genotypes 1, 2, or 3 (C-CREST-1 and C-CREST-2, part A)

    DEFF Research Database (Denmark)

    Gane, Edward J; Pianko, Stephen; Roberts, Stuart K

    2017-01-01

    BACKGROUND: New hepatitis C virus (HCV) therapies with pan-genotypic efficacy are needed. The goals of part A of C-CREST-1 and C-CREST-2 were to compare the efficacies of two doses (300 mg or 450 mg once daily) of uprifosbuvir (MK-3682; NS5B inhibitor) in an 8-week regimen combined with grazoprev...

  20. Pharmacokinetic interaction study of indinavir/ritonavir and the enteric-coated capsule formulation of didanosine in healthy volunteers.

    NARCIS (Netherlands)

    Porte, C.J.L. la; Verweij-van Wissen, C.P.W.G.M.; Ewijk, N. van; Aarnoutse, R.E.; Koopmans, P.P.; Reiss, P.; Stek Jr, M.; Hekster, Y.A.; Burger, D.M.

    2005-01-01

    Didanosine enteric-coated should be taken on an empty stomach, but the once-daily combination of indinavir/ritonavir can be taken with food. Because these drugs are frequently included in 1 regimen, the food effects on the pharmacokinetics were evaluated. This was a randomized, 4-way crossover study

  1. A randomised, open-label study of umeclidinium versus glycopyrronium in patients with COPD

    Directory of Open Access Journals (Sweden)

    Tara Rheault

    2016-04-01

    Full Text Available This study compared the efficacy and safety of once-daily umeclidinium 62.5 µg with once-daily glycopyrronium 50 µg in patients with moderate-to-severe chronic obstructive pulmonary disease. This was a 12-week, multicentre, randomised, open-label, parallel-group study (Clinicaltrials.gov: NCT02236611. Patients were randomised 1:1 to umeclidinium 62.5 µg or glycopyrronium 50 µg administered via Ellipta or Breezhaler dry powder inhaler, respectively. The primary endpoint was trough forced expiratory volume in 1 s (FEV1 at day 85 in the per-protocol population. Other endpoints included: weighted mean FEV1 over 0–24 h and patient-reported outcomes (transition dyspnoea index score and St George's Respiratory Questionnaire total score. Adverse events were also assessed. A total of 1037 patients were randomised to treatment. Umeclidinium was non-inferior (margin: −50 mL to glycopyrronium (trough FEV1 at day 85 treatment difference: 24 mL, 95% confidence intervals: −5–54. Improvements in other endpoints were similar between treatments. Adverse event incidences were similar for umeclidinium (37% and glycopyrronium (36%. Once-daily umeclidinium was non-inferior to once-daily glycopyrronium in patients with chronic obstructive pulmonary disease in trough FEV1 at day 85. Patient-reported outcomes and safety profiles were similar for both treatments.

  2. A randomised, open-label study of umeclidinium versus glycopyrronium in patients with COPD.

    Science.gov (United States)

    Rheault, Tara; Khindri, Sanjeev; Vahdati-Bolouri, Mitra; Church, Alison; Fahy, William A

    2016-04-01

    This study compared the efficacy and safety of once-daily umeclidinium 62.5 µg with once-daily glycopyrronium 50 µg in patients with moderate-to-severe chronic obstructive pulmonary disease. This was a 12-week, multicentre, randomised, open-label, parallel-group study (Clinicaltrials.gov: NCT02236611). Patients were randomised 1:1 to umeclidinium 62.5 µg or glycopyrronium 50 µg administered via Ellipta or Breezhaler dry powder inhaler, respectively. The primary endpoint was trough forced expiratory volume in 1 s (FEV1) at day 85 in the per-protocol population. Other endpoints included: weighted mean FEV1 over 0-24 h and patient-reported outcomes (transition dyspnoea index score and St George's Respiratory Questionnaire total score). Adverse events were also assessed. A total of 1037 patients were randomised to treatment. Umeclidinium was non-inferior (margin: -50 mL) to glycopyrronium (trough FEV1 at day 85 treatment difference: 24 mL, 95% confidence intervals: -5-54). Improvements in other endpoints were similar between treatments. Adverse event incidences were similar for umeclidinium (37%) and glycopyrronium (36%). Once-daily umeclidinium was non-inferior to once-daily glycopyrronium in patients with chronic obstructive pulmonary disease in trough FEV1 at day 85. Patient-reported outcomes and safety profiles were similar for both treatments.

  3. A Preference Study of Two Placebo Dry Powder Inhalers in Adults with COPD: ELLIPTA® Dry Powder Inhaler (DPI) versus DISKUS® DPI.

    Science.gov (United States)

    Yun Kirby, Suyong; Zhu, Chang-Qing; Kerwin, Edward M; Stanford, Richard H; Georges, George

    2016-01-01

    Patients' preference is an important factor in selecting an inhaler treatment for COPD. The DISKUS® dry powder inhaler (DPI), which has been available to deliver several COPD medications for a decade, and the ELLIPTA® DPI, developed for the delivery of newer once-daily medications for patients with COPD, were studied in terms of patient preference and inhaler-specific attributes. We conducted a randomized, open-label, crossover study in patients with COPD. Patients used placebo ELLIPTA DPI once daily and placebo DISKUS DPI twice daily, for ∼1 week each, while continuing their COPD medications. Endpoints were: inhaler preference based on size of the numbers on the dose-counter (primary); the number of steps needed and inhaler size (secondary); and based on comfort of the mouthpiece, ease of opening, overall preference, and dosing regimen preference ('other'). Safety assessments included adverse events (AEs). A total of 287 patients were randomized. A significantly (p ELLIPTA DPI over DISKUS DPI for each of the tested attributes and overall, and preferred once-daily over twice-daily dosing. AEs were reported for 36 patients (13%); one (dry mouth) was considered to be related to the placebo-containing DISKUS DPI. Three patients had five non-fatal serious AEs, none were deemed inhaler-related. This study demonstrated that more patients with COPD preferred five specific inhaler attributes of the ELLIPTA DPI over DISKUS DPI and overall, and preferred once-daily versus twice-daily dosing. Safety profiles were consistent with those expected for COPD.

  4. Phase II study of oral fingolimod (FTY720) in multiple sclerosis: 3-year results

    DEFF Research Database (Denmark)

    Comi, G; O'Connor, P; Montalban, X;

    2010-01-01

    In a 6-month, placebo-controlled trial, oral fingolimod (FTY720) 1.25 or 5.0 mg, once daily, significantly reduced MRI inflammatory activity and annualized relapse rate compared with placebo in patients with relapsing multiple sclerosis (MS). The objectives were to monitor the 36-month, interim e...

  5. Liraglutide as adjunct to insulin treatment in type 1 diabetes does not interfere with glycaemic recovery or gastric emptying rate during hypoglycaemia

    DEFF Research Database (Denmark)

    Frandsen, Christian Seerup; Dejgaard, Thomas Fremming; Andersen, Henrik Ullits

    2017-01-01

    .2 mg once daily or placebo as add-on to insulin treatment. Before and at end of treatment a hypoglycaemic clamp (plasma glucose target 2.5 mmol/l) was carried out followed by a liquid meal. Primary endpoint was change in GE rate (evaluated by area under the paracetamol curve and time to peak...

  6. A randomized, controlled trial of 3.0 mg of Liraglutide in weight management

    DEFF Research Database (Denmark)

    Pi-Sunyer, Xavier; Astrup, Arne; Fujioka, Ken

    2015-01-01

    Background Obesity is a chronic disease with serious health consequences, but weight loss is difficult to maintain through lifestyle intervention alone. Liraglutide, a glucagon-like peptide-1 analogue, has been shown to have potential benefit for weight management at a once-daily dose of 3.0 mg, ...

  7. Renal hemodynamic effects of candesartan in normal and impaired renal function in humans

    NARCIS (Netherlands)

    Buter, H; Navis, G; deZeeuw, D; deJong, PE

    1997-01-01

    The effects of angiotensin II type I receptor antagonist candesartan cilexitil, 8 mg once daily, were studied after single dose and after five days treatment in 17 hypertensive patients [median mean arterial pressure (MAP) 118 mm Hg, range 84 to 134] with renal function impairment of different sever

  8. Angiotensin receptor blockade in acute stroke. The Scandinavian Candesartan Acute Stroke Trial

    DEFF Research Database (Denmark)

    Sandset, Else Charlotte; Murray, Gordon; Boysen, Gudrun

    2010-01-01

    ≥140 mmHg. The recruited patients are randomly assigned to candesartan or placebo for 7-days (doses increasing from 4 to 16 mg once daily). Randomisation is performed centrally via a secure web interface. The follow-up period is 6-months. Patients are included from the following nine North...

  9. Angiotensin receptor blockade in acute stroke. The Scandinavian Candesartan Acute Stroke Trial: rationale, methods and design of a multicentre, randomised- and placebo-controlled clinical trial (NCT00120003)

    DEFF Research Database (Denmark)

    Sandset, Else Charlotte; Murray, Gordon; Boysen, Gudrun Margrethe

    2010-01-01

    Hg. The recruited patients are randomly assigned to candesartan or placebo for 7-days (doses increasing from 4 to 16 mg once daily). Randomisation is performed centrally via a secure web interface. The follow-up period is 6-months. Patients are included from the following nine North-European countries: Norway...

  10. Safety and Proof-of-Concept Study of Oral QLT091001 in Retinitis Pigmentosa Due to Inherited Deficiencies of Retinal Pigment Epithelial 65 Protein (RPE65) or Lecithin:Retinol Acyltransferase (LRAT): e0143846

    National Research Council Canada - National Science Library

    Hendrik P N Scholl; Anthony T Moore; Robert K Koenekoop; Yuquan Wen; Gerald A Fishman; Ingeborgh van den Born; Ava Bittner; Kristen Bowles; Emily C Fletcher; Frederick T Collison; Gislin Dagnelie; Simona Degli Eposti; Michel Michaelides; David A Saperstein; Ronald A Schuchard; Claire Barnes; Wadih Zein; Ditta Zobor; David G Birch; Janine D Mendola; Eberhart Zrenner

    2015-01-01

    ...). Safety and visual outcomes of a once-daily oral dose of 40 mg/m2/day QLT091001 for 7 consecutive days was investigated in an international, multi-center, open-label, proof-of-concept study in 18...