title: Gender differences in pharmacokinetics of maintenance dosed buprenorphine.
abstract: OBJECTIVE
  Gender differences are known to occur in the pharmacokinetics of many drugs. Mechanisms may include differences in body composition, body weight, cardiac output, hormonal status, and use of different co-medications. Recently subtle gender-dependent differences in cytochrome P450 (CYP) 3A-dependent metabolism have been demonstrated. Buprenorphine N-dealkylation to norbuprenorphine is primarily performed by CYP3A. We therefore asked whether gender-dependent differences occur in the pharmacokinetics of buprenorphine.
  
  
  METHODS
  A retrospective examination was made of control (buprenorphine/naloxone-only) sessions from a number of drug interaction studies between buprenorphine and antiretroviral drugs. Twenty males and eleven females were identified who had a negative cocaine urine test prior to participation in the control session and were all on the same maintenance dose (16/4 mg) of sublingual buprenorphine/naloxone. Pharmacokinetic data from their control sessions (buprenorphine/naloxone only) were sorted by gender and compared using the two-sample t-test.
  
  
  RESULTS
  Females had significantly higher area under the plasma concentration curve (AUC) and maximum plasma concentrations for buprenorphine, norbuprenorphine and norbuprenorphine-3-glucuronide. AUCs relative to dose per body weight and surface area were significantly higher for only norbuprenorphine. AUCs relative to lean body mass were, however, not significantly different.
  
  
  CONCLUSIONS
  Gender-related differences exist in the pharmacokinetics of buprenorphine; differences in body composition appear to have a major impact; differences in CYPA-dependent metabolism may also contribute.
authors.affiliation: Center for Human Toxicology, Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT 84108, USA. david.moody@utah.edu
authors.forename: David E
authors.initials: DE
authors.lastname: Moody
authors.forename: Wenfang B
authors.initials: WB
authors.lastname: Fang
authors.forename: Jerdravee
authors.initials: J
authors.lastname: Morrison
authors.forename: Elinore
authors.initials: E
authors.lastname: McCance-Katz
mesh_terms: D000328:Adult; D002047:Buprenorphine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009294:Narcotics / Q000008:administration & dosage / Q000493:pharmacokinetics*; D012189:Retrospective Studies; D012727:Sex Characteristics
chemical_list: D009294:Narcotics; D002047:Buprenorphine