Pharmacokinetics of buprenorphine in pregnant sheep after intravenous injection

Henriikka Hakomäki, Hannu Kokki, Marko Lehtonen, Veli-Pekka Ranta, Juha Räsänen, Hanna-Marja Voipio, Merja Kokki

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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 mu g/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 mu g/L and 0.04 mu g/L for buprenorphine and norbuprenorphine, respectively. The pharmacokinetic parameters were calculated using noncompartmental analysis. The pharmacokinetic parameters, median (minimum-maximum), were C-max 4.31 mu g/L (1.93-15.5), AUC(inf) 2.89 h*mu g/L (1.72-40.2), CL 3.39 L/h/kg (0.25-6.02), terminal t1/2 1.75 h (1.07-31.0), V-ss 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.

Original languageEnglish
Article number00726
JournalPharmacology Research & Perspectives
Issue number2
Number of pages7
Publication statusPublished - Apr 2021
MoE publication typeA1 Journal article-refereed

Fields of Science

  • 317 Pharmacy
  • buprenorphine
  • pharmacokinetics
  • pregnancy
  • sheep

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