Voriconazole greatly increases the exposure to oral buprenorphine

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http://hdl.handle.net/10138/268045

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Fihlman , M , Hemmilä , T , Hagelberg , N M , Backman , J T , Laitila , J , Laine , K , Neuvonen , P J , Olkkola , K T & Saari , T I 2018 , ' Voriconazole greatly increases the exposure to oral buprenorphine ' , European Journal of Clinical Pharmacology , vol. 74 , no. 12 , pp. 1615-1622 . https://doi.org/10.1007/s00228-018-2548-8

Title: Voriconazole greatly increases the exposure to oral buprenorphine
Author: Fihlman, Mari; Hemmilä, Tuija; Hagelberg, Nora M.; Backman, Janne T.; Laitila, Jouko; Laine, Kari; Neuvonen, Pertti J.; Olkkola, Klaus T.; Saari, Teijo I.
Contributor: University of Helsinki, Department of Clinical Pharmacology
University of Helsinki, Department of Clinical Pharmacology
University of Helsinki, Medicum
University of Helsinki, Department of Diagnostics and Therapeutics
Date: 2018-12
Language: eng
Number of pages: 8
Belongs to series: European Journal of Clinical Pharmacology
ISSN: 0031-6970
URI: http://hdl.handle.net/10138/268045
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
Subject: Buprenorphine
Norbuprenorphine
Voriconazole
Pharmacokinetics
Drug-drug interaction
CYP3A4
Transporters
HUMAN LIVER-MICROSOMES
IN-VITRO METABOLISM
P-GLYCOPROTEIN
SUBLINGUAL BUPRENORPHINE
CLINICAL PHARMACOKINETICS
SYSTEMIC ANTIMYCOTICS
MAINTENANCE THERAPY
CYTOCHROME-P450 3A4
OPIOID DEPENDENCE
N-DEALKYLATION
3111 Biomedicine
317 Pharmacy
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