کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6015679 1186075 2014 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Reassessment of stiripentol pharmacokinetics in healthy adult volunteers
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی عصب شناسی
پیش نمایش صفحه اول مقاله
Reassessment of stiripentol pharmacokinetics in healthy adult volunteers
چکیده انگلیسی


- We assessed the pharmacokinetics of stiripentol in 12 healthy volunteers.
- No concentration rebound was observed during its disposition phase.
- The elimination half-life could be estimated for the first time.
- The non-linear pharmacokinetics of stiripentol was confirmed.

SummaryBecause children who have been receiving stiripentol for the treatment of Dravet syndrome for more than 10 years are now becoming young adults, it is important to accurately characterize stiripentol pharmacokinetics in this age range. A double-blind placebo-controlled dose ranging study was therefore conducted to investigate the pharmacokinetics and tolerability of stiripentol in 12 healthy volunteers. Each subject received 3 single doses of stiripentol (500, 1000, and 2000 mg) separated by a wash-out period of 1 week. Pharmacokinetics of stiripentol was analyzed for each dose by non-compartmental analysis. Median area under the curve (AUC), terminal elimination half-life (t1/2,z) and maximal concentration (Cmax) were calculated for between-dose comparison. Safety was evaluated based on both clinical and biological criteria. Oppositely to previous results, there was no concentration rebounds in the elimination phase, which could be the consequence of the food intake. A more than proportional increase in the AUC was observed, associated with a significant increase in the t1/2,z, for increasing doses (median AUC of 8.3, 31 and 88 mg h/L, and median t1/2,z of 2, 7.7 and 10 h for the 500, 1000, and 2000 mg doses respectively), which confirmed the Michaelis-Menten pharmacokinetics of Stiripentol. However, dose-normalized Cmax did not significantly vary between doses. Median Michaelis-Menten parameters were 117 mg/h for Vmax and 1.9 mg/L for Km. No safety concern was observed during the study. The present study allowed a better characterization of the disposition phase of stiripentol and confirmed its non-linear pharmacokinetic behaviour. Further pharmacokinetic/pharmacodynamic studies would be useful to determine the optimal dose of stiripentol for the treatment of Dravet patients in adulthood.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Epilepsy Research - Volume 108, Issue 5, July 2014, Pages 909-916
نویسندگان
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