Pharmacokinetic interaction between efavirenz and rifampicin in healthy volunteers

Objective: Rifampicin induces the metabolism of efavirenz in humans. This study evaluated efavirenz bioavailability after rifampicin administration to healthy volunteers. Methods: A 3-week, before-and-after trial was performed on 8 healthy volunteers. The pharmacokinetic parameters were: plasma drug concentration-time profile from 0 to 72 h (AUC(0-72)), plasma drug concentration-time profile from 0 h to infinity (AUC(0-inf)), maximal drug concentration (C-max), time to reach maximal drug concentration (t(max)), and time to reach half the initial drug concentration in elimination phase (t(1/2)). After an overnight fast, the volunteers ingested one efavirenz 600 mg tablet, then blood samples were drawn to evaluate plasma efavirenz levels at 0, 2, 3, 4, 5, 6, 24, 72, 120, and 168 h. The procedure was repeated after a 1-week induction period of 450 mg/day. Paired-t test and Wilcoxon matched-pairs test were used for differences between mean concentrations. Results: Baseline mean AUC(0-72) was 46.80 +/- 9.27 mu g/ml.h, AUC(0-inf) was 96.38 +/- 38.10 mu g/ml.h, C-max 2.19 +/- 0.68 mu g/ml.h, t(max) 4.50 +/- 0.93 h, and t(1/2), 96.60 +/- 42.38 h. Post-induction values were significantly increased: AUC(0-72) 9.53 +/- 11.26 mu g/ml.h (p < 0.05; CI95% = 0.112 - 18.940), AUC(0-inf) 37.24 +/- 42.43 (p < 0.05; CI95% = 0.021 - 0.406) mu g/ml.h, and t(max) 1.13 +/- 0.99 h (p < 0.05; CI95% = 0.296 - 1.953). No significant reduction occurred in post-rifampicin induction means of C-max and t(1/2). Conclusion: Co-administration of a single dose of efavirenz 600 mg/day with 1-week rifampicin 450 mg/day significantly reduced efavirenz bioavailability in healthy volunteers.