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

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 of 800 mg,threetimes a day,was compared to 2400 mg given once a day.Under ideal conditions,the predicted maximum drug in the total colon and individual colonic segments over 100 d differed by less than 3%between single and multiple doses.Despite changes in motility and defection rates,the predicted maximum and average 5-ASA concentrations in the total colon and individual colonic segments differed by less than 10%between dosing regimens.Asymmetric distribution of 5-ASA in the colon was influenced by frequency of bowel movements and colonic transit rate.In active colitis,sigmoid 5-ASA concentration becomes negligible.Our model supports once daily administration of Asacol as standard treatment for ulcerative colitis.

Safety and Efficacy of Once-Daily Administration of Mycophenolate Mofetil in Kidney Transplant Patients—A New Treatment Option for Non-Adherence

Non-adherence to immunosuppressive therapy is associated with reduced graft survival. Fifteen long-term follow up kidney transplant patients with stable post-transplant clinical courses were enrolled in the study. All patients were prescribed to tacrolimus prolonged release, mycophenolate mofetil (MMF) and corticosteroid at the time of enrolment. Twice-daily administration of MMF was then converted to a single daily dose. As a result, all immunosuppressive agents were administered simultaneously at one time in the morning. The daily total doses of the three immunosuppressants were identical during the study period. No acute rejection or adverse event was observed during the study period. Blood urea nitrogen and estimated glomerular filtration rate did not change significantly after conversion to once-daily administration. The blood tacrolimus trough level and the Mycophenolic acid (MPA) trough level also did not change significantly after conversion to once-daily administration. Interestingly, the meanmedian MPA trough level remained >3 μg/ml even after conversion to once-daily administration. A sufficient plasma MPA level was maintained after conversion to once-daily administration, and no acute rejection was observed during the study period. To our knowledge, this study is the first to report that the plasma MPA concentration can be maintained after once-daily administration of MMF in long-term kidney transplant patients. Once-daily administration of immunosuppressive agents may improve long-term graft survival because of better treatment adherence due to the reduced dosing frequency. The safety or efficacy of conversion to once-daily administration of MMF should be evaluated in a future randomized controlled large-scale clinical study.

Evaluation of the long-term safety and effectiveness of tadalafil once daily in Chinese men with erectile dysfunction： interim results of a multicenter, randomized, open-label trial

Once-daily tadalafil administration has been well established; however, studies about tadalafil once-daily treatment in the Chinese population are lacking. In this phase 4, postmarketing study, we ascertained the long-term safety and effectiveness of tadalafil 2.5 mg and 5.0 mg once daily in Chinese men with erectile dysfunction （n = 635）. The primary endpoint of the study was safety at 12 months as assessed by the proportion of patients experiencing at least one treatment-emergent adverse event （serious or nonserious）. The secondary endpoints included safety and effectiveness, measured by the International Index of Erectile Function-Erectile Function （IIEF-EF） domain scores. Similar adverse events to the known safety profile of tadalafil, such as nasopharyngitis, upper respiratory tract infection, headache, and dizziness, were detected. No new cardiovascular safety concerns were observed. After 3 months of treatment, significant increases in IIEF-EF domain scores were detected for both 2.5-mg （least squares [LS] mean change： 6.3; 95% confidence interval [CI]： 5.4-7.1; P 〈 0.001） and 5.0-mg （LS mean change： 7.4; 95% CI： 6.8-7.9; P 〈 0.001） tadalafil doses, and significance was maintained up to 12 months. In addition, approximately 40% of patients regained normal erectile function （IIEF-EF 〉26） following 1 year of tadalafil once-daily treatment. The findings in this study provide evidence for the extended effectiveness and tolerability of tadalafil, demonstrating no new safety concerns, in a Chinese population and make once-daily tadalafil administration a viable option for improving sexual performance and satisfaction in Chinese men with erectile dysfunction.

Long-term tadalafil once daily in Chinese men witherectile dysfunction:a 2-year final analysis of apost-marketing,multicenter,randomized,open-labeltrial

The long-term safety and effectiveness of once-daily tadalafil is crucial,but limited data are available in Chinese patients witherectile dysfunction(ED).In this post-marketing,multicenter,randomized,open-label trial with 2-year follow-up,635 ED caseswere randomized to receive daily oral tadalafil 2.5 mg or 5 mg for 3 months,of whom 580 continued once-daily tadalafil 5 mg for21 months.Treatment-emergent adverse events in the 12-month and 24-month period were similar,with the most common beingviral upper respiratory tract infection,upper respiratory tract infection,and headache.Significant improvement from baseline inthe International Index of Erectile Function-Erectile Function(IIEF-EF)score was detected at month 12(least squares mean[LSM]change:7.9,95%confidence interval[CI]:7.5–8.4,P<0.001)and was maintained to month 24(LSM change:8.6,95%CI:8.1–9.0,P<0.001).The proportions of patients regaining normal erectile function(IIEF-EF score≥26)were 43.7%and 48.0%at months 12 and 24,respectively.Global Assessment Questionnaire results showed improved erection function in 97.5%ofpatients and improved ability to engage in sexual activity in 95.9%of patients at month 12;these values were 96.1%and 95.0%at month 24,respectively.The quality of sexual life score based on the Sexual Life Quality Questionnaire(SLQQ)was increased by52.2%at month 12 and by 55.3%at month 24(both P<0.001).The treatment satisfaction score determined by SLQQ(mean±standard deviation)was 62.4±21.0 at month 12 versus 65.9±20.2 at month 24.Two-year daily application of tadalafil 5mg in Chinese men with ED showed a favorable safety profile and durable improvement in sexual performance and satisfaction.