Pharmacokinetic interaction between efavirenz and carbamazepine after multiple-dose administration in healthy subjects.
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 [AUCtau], 0.64 [0.60-0.68]; maximum plasma concentration [C(max)], 0.79 [0.74, 0.85]) and carbamazepine (AUC(tau), 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(tau), 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.
Ji
Ping
P
Bristol-Myers Squibb Research and Development, Mail Stop E1215, Route 206 & Province Line Road, Princeton, NJ 08543, USA. pingji@bms.com
Damle
Bharat
B
Xie
Jingdong
J
Unger
Steve E
SE
Grasela
Dennis M
DM
Kaul
Sanjeev
S
D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000927:Anticonvulsants / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D048588:Benzoxazines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001711:Biotransformation; D002220:Carbamazepine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D003521:Cyclopropanes; D004347:Drug Interactions; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D018401:Sample Size
D000480:Alkynes; D019380:Anti-HIV Agents; D000927:Anticonvulsants; D048588:Benzoxazines; D003521:Cyclopropanes; D002220:Carbamazepine; C098320:efavirenz; C012227:carbamazepine epoxide