کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6015398 1579910 2015 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Brivaracetam and carbamazepine interaction in healthy subjects and in vitro
ترجمه فارسی عنوان
تعامل بلورواستات و کاربامازپین در افراد سالم و در شرایط آزمایشگاهی
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی عصب شناسی
چکیده انگلیسی


- Phase I interaction study (brivaracetam, carbamazepine) in 14 healthy subjects.
- Brivaracetam did not significantly alter carbamazepine exposure.
- Brivaracetam increased carbamazepine-epoxide exposure by 2.6-fold.
- In vitro hydrolysis of carbamazepine-epoxide was inhibited by brivaracetam.
- Enzyme induction by carbamazepine led to modest reduction in brivaracetam exposure.

This phase I, open-label study investigated the effects of steady-state brivaracetam administration on steady-state pharmacokinetics of carbamazepine, and steady-state carbamazepine administration on single-dose and steady-state pharmacokinetics of brivaracetam, in 14 healthy participants who received brivaracetam 200 mg single doses on days 1 and 22, and 200 mg twice daily (bid) on days 24-35; and were titrated to carbamazepine 300 mg bid on days 4-35. Brivaracetam did not significantly alter carbamazepine area under the plasma concentration-time curve (AUC) over a dosing interval, but resulted in a 2.6-fold increase in carbamazepine-epoxide. Carbamazepine decreased brivaracetam AUC by 29%, while hydroxy-brivaracetam metabolite was increased by 17%. Urinary 6β-hydroxycortisol/cortisol ratio was unchanged by brivaracetam, but was increased 3-fold by carbamazepine. In vitro hydrolysis of carbamazepine-epoxide in human hepatocytes was inhibited by brivaracetam, with an IC50 of 8.2 μM. Brivaracetam 200 mg bid was predicted to increase carbamazepine-epoxide by 2.3-fold, in close agreement with the observed value. In conclusion, brivaracetam did not modify carbamazepine exposure but increased carbamazepine-epoxide. Carbamazepine modestly decreased brivaracetam exposure and increased oxidative metabolism.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Epilepsy Research - Volume 113, July 2015, Pages 19-27
نویسندگان
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