Premium
Pharmacokinetic Interaction Between Efavirenz and Carbamazepine After Multiple‐Dose Administration in Healthy Subjects
Author(s) -
Ji Ping,
Damle Bharat,
Xie Jingdong,
Unger Steve E.,
Grasela Dennis M.,
Kaul Sanjeev
Publication year - 2008
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270008319792
Subject(s) - carbamazepine , efavirenz , pharmacokinetics , crossover study , pharmacology , confidence interval , dosing , pharmacokinetic interaction , drug interaction , active metabolite , metabolite , medicine , chemistry , antiretroviral therapy , epilepsy , viral load , human immunodeficiency virus (hiv) , immunology , alternative medicine , pathology , psychiatry , placebo
The effect of efavirenz on the pharmacokinetics of carbamazepine and vice versa was investigated in adult healthy subjects in a randomized, open‐label, 2‐period crossover, multiple‐dose study. Subjects were randomized to receive either efavirenz 600 mg qd for 14 days or carbamazepine titrated to 400 mg qd for 21 days followed with both drugs for another 21 or 14 days. The pharmacokinetics was evaluated for efavirenz, carbamazepine, and the major metabolite of carbamazepine, carbamazepine‐10,11‐epoxide. Coadministration of carbamazepine with efavirenz significantly reduced the exposure of efavirenz (geometric mean ratios [90% confidence interval]: area of plasma concentration‐time curve during the dosing interval of 24 hours [AUCτ], 0.64 [0.60–0.68]; maximum plasma concentration [C max ], 0.79 [0.74, 0.85]) and carbamazepine (AUC τ , 0.73 [0.67–0.80]; C max , 0.80 [0.76, 0.85]) but had minimal impact on the exposure of carbamazepine‐10,11‐epoxide (AUC τ , 0.99 [0.85–1.15]; C max , 1.05 [0.91, 1.22]). In summary, a 2‐way pharmacokinetic interaction between efavirenz and carbamazepine was demonstrated in this study.