Urinary excretion of buprenorphine, norbuprenorphine, buprenorphine- glucuronide, and norbuprenorphine-glucuronide in pregnant women receiving buprenorphine maintenance treatment

Sherri L. Kacinko, Hendree E. Jones, Rolley E. Johnson, Robin E. Choo, Marta Concheiro-Guisan, Marilyn A. Huestis

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Buprenorphine (BUP) is under investigation as a medication therapy for opioid-dependent pregnant women.Weinvestigated 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 μg/L for BUP and BUP-Gluc and 25 μg/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.

Original languageEnglish (US)
Pages (from-to)1177-1187
Number of pages11
JournalClinical chemistry
Volume55
Issue number6
DOIs
StatePublished - Jun 1 2009

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Biochemistry, medical

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