title: Urinary excretion of buprenorphine, norbuprenorphine, buprenorphine-glucuronide, and norbuprenorphine-glucuronide in pregnant women receiving buprenorphine maintenance treatment.
abstract: BACKGROUND
  Buprenorphine (BUP) is under investigation as a medication therapy for opioid-dependent pregnant women. We investigated BUP and metabolite disposition in urine from women maintained on BUP during the second and third trimesters of pregnancy and postpartum.
  
  
  METHODS
  We measured BUP, norbuprenorphine (NBUP), buprenorphine glucuronide (BUP-Gluc), and NBUP-Gluc concentrations in 515 urine specimens collected thrice weekly from 9 women during pregnancy and postpartum. Specimens were analyzed using a fully validated liquid chromatography-mass spectrometry method with limits of quantification of 5 microg/L for BUP and BUP-Gluc and 25 microg/L for NBUP and its conjugated metabolite. We examined ratios of metabolites across trimesters and postpartum to identify possible changes in metabolism during pregnancy.
  
  
  RESULTS
  NBUP-Gluc was the primary metabolite identified in urine and exceeded BUP-Gluc concentrations in 99% of specimens. Whereas BUP-Gluc was identified in more specimens than NBUP, NBUP exceeded BUP-Gluc concentrations in 77.9% of specimens that contained both analytes. Among all participants, the mean BUP-Gluc:NBUP-Gluc ratio was significantly higher in the second trimester compared to the third trimester, and there were significant intrasubject differences between trimesters in 71% of participants. In 3 women, the percent daily dose excreted was higher during pregnancy than postpregnancy, consistent with other data indicating increased renal elimination of drugs during pregnancy.
  
  
  CONCLUSIONS
  These data are the first to evaluate urinary disposition of BUP and metabolites in a cohort of pregnant women. Variable BUP excretion during pregnancy may indicate metabolic changes requiring dose adjustment during later stages of gestation.
authors.affiliation: Chemistry and Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse, NIH, Baltimore, MD, USA.
authors.forename: Sherri L
authors.initials: SL
authors.lastname: Kacinko
authors.forename: Hendree E
authors.initials: HE
authors.lastname: Jones
authors.forename: Rolley E
authors.initials: RE
authors.lastname: Johnson
authors.forename: Robin E
authors.initials: RE
authors.lastname: Choo
authors.forename: Marta
authors.initials: M
authors.lastname: Concheiro-Guisan
authors.forename: Marilyn A
authors.initials: MA
authors.lastname: Huestis