Clinical Chemistry
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Clinical Chemistry 55: 1177-1187, 2009. First published March 26, 2009; 10.1373/clinchem.2008.113712
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(Clinical Chemistry. 2009;55:1177-1187.)
© 2009 American Association for Clinical Chemistry, Inc.

Drug Monitoring and Toxicology

Urinary Excretion of Buprenorphine, Norbuprenorphine, Buprenorphine-Glucuronide, and Norbuprenorphine-Glucuronide in Pregnant Women Receiving Buprenorphine Maintenance Treatment

Sherri L. Kacinko1, Hendree E. Jones2, Rolley E. Johnson2,3, Robin E. Choo4, Marta Concheiro-Guisan1 and Marilyn A. Huestis1,a

1 Chemistry and Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse, NIH, Baltimore, MD;2 Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD;3 Reckitt Benckiser Pharmaceuticals Inc., Richmond, VA;4 Department of Biology, University of Pittsburgh at Titusville, Titusville, PA.

aAddress correspondence to this author at: 251 Bayview Blvd., Suite 05A-721, Baltimore, MD 21224. Fax 443-740-2823; e-mail mhuestis{at}intra.nida.nih.gov.

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 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. .






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Copyright © 2009 by the American Association for Clinical Chemistry.