University of Oulu

Hakomäki, H., Kokki, H., Lehtonen, M., Ranta, V.‐P., Räsänen, J., Voipio, H.‐M. and Kokki, M. (2021), Pharmacokinetics of buprenorphine in pregnant sheep after intravenous injection. Pharmacol Res Perspect, 9: e00726. https://doi.org/10.1002/prp2.726

Pharmacokinetics of buprenorphine in pregnant sheep after intravenous injection

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Author: Hakomäki, Henriikka1; Kokki, Hannu2; Lehtonen, Marko1;
Organizations: 1School of Pharmacy, University of Eastern Finland, Kuopio, Finland
2School of Medicine, University of Eastern Finland, Kuopio, Finland
3Department of Obstetrics and Gynecology, Helsinki University Hospital, Helsinki, Finland
4Department of Experimental Surgery, Oulu Laboratory Animal Centre, Oulu University Hospital and University of Oulu, Oulu, Finland
5Department of Anesthesia and Intensive Care, Kuopio University Hospital, Kuopio, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.6 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe2021050629059
Language: English
Published: John Wiley & Sons, 2021
Publish Date: 2021-05-06
Description:

Abstract

Buprenorphine is a semi‐synthetic opioid, widely used in the maintenance treatment for opioid‐dependent pregnant women. Limited data exist on the pharmacokinetics of buprenorphine in pregnancy. We conducted a pharmacokinetic study to determine the pharmacokinetics of intravenous buprenorphine in pregnant sheep. Fourteen pregnant sheep in late gestation received 10 µg/kg of buprenorphine as an intravenous bolus injection. Plasma samples were collected up to 48 h after administration. Buprenorphine and its metabolite, norbuprenorphine, were quantified from plasma using a LC/MS/MS method, with lower limits of quantification of 0.01 µg/L and 0.04 µg/L for buprenorphine and norbuprenorphine, respectively. The pharmacokinetic parameters were calculated using noncompartmental analysis. The pharmacokinetic parameters, median (minimum−maximum), were Cmax 4.31 µg/L (1.93–15.5), AUCinf 2.89 h*µg/L (1.72–40.2), CL 3.39 L/h/kg (0.25–6.02), terminal t½ 1.75 h (1.07–31.0), Vss 8.04 L/kg (1.05–49.3). Norbuprenorphine was undetected in all plasma samples. The median clearance in pregnant sheep was higher than previously reported for nonpregnant sheep and human (male) subjects. Our sensitive analytical method was able to detect long terminal half‐lives for six subjects, and a wide between‐subject variability in the study population.

Significance statement: Buprenorphine is widely used for the treatment of opioid use disorder in pregnancy. However, limited data exist on the pharmacokinetics of buprenorphine during pregnancy. As this type of study cannot be done in humans due to ethical reasons, we conducted a study in pregnant sheep. This study provides pharmacokinetic data on buprenorphine in pregnant sheep and helps us to understand the pharmacokinetics of the drug in humans.

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Series: Pharmacology research & perspectives
ISSN: 2052-1707
ISSN-E: 2052-1707
ISSN-L: 2052-1707
Volume: 9
Issue: 2
Article number: e00726
DOI: 10.1002/prp2.726
OADOI: https://oadoi.org/10.1002/prp2.726
Type of Publication: A1 Journal article – refereed
Field of Science: 317 Pharmacy
Subjects:
Funding: OLVI‐Säätiö. Grant Number: 201820259; The Finnish Concordia Fund. Grant Number: 20200226.
Copyright information: © 2021 The Authors. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
  https://creativecommons.org/licenses/by/4.0/