獣医科学と技術

Buprenorphine Pharmacokinetics Following Intravenous Administration in Gestating Sheep

Abstract

Hari Prasad Sonwani*

Pregnant women who are addicted on opioids are frequently treated with buprenorphine, a semi-synthetic opioid. Pregnancy-related buprenorphine pharmacokinetics is little studied. To find out the pharmacokinetics of intravenous buprenorphine in pregnant sheep, we performed a pharmacokinetic study. An intravenous bolus injection containing 10 μg/kg of buprenorphine was administered to 14 pregnant sheep with late gestation. Plasma samples were taken for up to 48 hours following administration. Using an LC/MS/MS approach, the levels of buprenorphine and its metabolite, nor buprenorphine, were measured in plasma. The lower limits of quantification for each drug were 0.01μg/L and 0.04μg/L, respectively. Noncompartmental analysis was used to calculate the pharma-cokinetic parameters. The median (minimum−maximum) pharmacokinetic characteristics were: Cmax 4.31 μg/L (1.93–15.5), AUCinf 2.89 h*μg/L (1.72–40.2), and CL 3.39 L/h/kg (0.25–Vss 8.04 L/kg (1.05–49.3), terminal t½ 1.75 h (1.07–31.0), and 6.02. Norbuprenorphine was not found in any of the plasma samples. Compared to non-pregnant sheep and male human participants, the median clearance in pregnant sheep was greater. Six subjects had extended terminal half-lives, and a high degree of betweensubject variability was found in the sample population using our sensitive analytical approach. Statement of significance: Pregnant women with opioid use disorder are frequently treated with buprenorphine. Nevertheless, there is a paucity of information regarding the pharmacokinetics of buprenorphine in pregnancy. We performed a study on pregnant sheep because this kind of research cannot be done on humans for ethical reasons. The pharmacokinetic information on buprenorphine in pregnant sheep provided by this study aids in our comprehension of the drug's pharmacokinetics in humans.