Voriconazole greatly increases the exposure to oral buprenorphine

Abstract

PurposeBuprenorphine has low oral bioavailability. Regardless of sublingual administration, a notable part of buprenorphine is exposed to extensive first-pass metabolism by the cytochrome P450 (CYP) 3A4. As drug interaction studies with buprenorphine are limited, we wanted to investigate the effect of voriconazole, a strong CYP3A4 inhibitor, on the pharmacokinetics and pharmacodynamics of oral buprenorphine.MethodsTwelve healthy volunteers were given either placebo or voriconazole (orally, 400mg twice on day 1 and 200mg twice on days 2-5) for 5days in a randomized, cross-over study. On day 5, they ingested 0.2mg (3.6mg during placebo phase) oral buprenorphine. We measured plasma and urine concentrations of buprenorphine and norbuprenorphine and monitored their pharmacological effects. Pharmacokinetic parameters were normalized for a buprenorphine dose of 1.0mg.ResultsVoriconazole greatly increased the mean area under the plasma concentration-time curve (AUC(0-18)) of buprenorphine (4.3-fold, P