{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T17:19:31Z","timestamp":1782321571836,"version":"3.54.5"},"reference-count":27,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,2,22]],"date-time":"2021-02-22T00:00:00Z","timestamp":1613952000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012691","name":"OLVI-S\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","award":["201820259"],"award-info":[{"award-number":["201820259"]}],"id":[{"id":"10.13039\/501100012691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacology Res &amp; Perspec"],"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Buprenorphine is a semi\u2010synthetic opioid, widely used in the maintenance treatment for opioid\u2010dependent 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\u00a0\u00b5g\/kg of buprenorphine as an intravenous bolus injection. Plasma samples were collected up to 48\u00a0h 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\u00a0\u00b5g\/L and 0.04\u00a0\u00b5g\/L for buprenorphine and norbuprenorphine, respectively. The pharmacokinetic parameters were calculated using noncompartmental analysis. The pharmacokinetic parameters, median (minimum\u2212maximum), were C<jats:sub>max<\/jats:sub> 4.31\u00a0\u00b5g\/L (1.93\u201315.5), <jats:italic>AUC<\/jats:italic><jats:sub>inf<\/jats:sub> 2.89\u00a0h*\u00b5g\/L (1.72\u201340.2), <jats:italic>CL<\/jats:italic> 3.39\u00a0L\/h\/kg (0.25\u20136.02), terminal t\u00bd 1.75\u00a0h (1.07\u201331.0), V<jats:sub>ss<\/jats:sub> 8.04 L\/kg (1.05\u201349.3). 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\u2010lives for six subjects, and a wide between\u2010subject variability in the study population.<\/jats:p><jats:p>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.<\/jats:p>","DOI":"10.1002\/prp2.726","type":"journal-article","created":{"date-parts":[[2021,2,23]],"date-time":"2021-02-23T02:04:57Z","timestamp":1614045897000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Pharmacokinetics of buprenorphine in pregnant sheep after intravenous injection"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8930-6951","authenticated-orcid":false,"given":"Henriikka","family":"Hakom\u00e4ki","sequence":"first","affiliation":[{"name":"School of Pharmacy University of Eastern Finland Kuopio Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannu","family":"Kokki","sequence":"additional","affiliation":[{"name":"School of Medicine University of Eastern Finland Kuopio Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marko","family":"Lehtonen","sequence":"additional","affiliation":[{"name":"School of Pharmacy University of Eastern Finland Kuopio Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veli\u2010Pekka","family":"Ranta","sequence":"additional","affiliation":[{"name":"School of Pharmacy University of Eastern Finland Kuopio Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juha","family":"R\u00e4s\u00e4nen","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Helsinki University Hospital Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna\u2010Marja","family":"Voipio","sequence":"additional","affiliation":[{"name":"Department of Experimental Surgery Oulu Laboratory Animal Centre Oulu University Hospital and University of Oulu Oulu Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merja","family":"Kokki","sequence":"additional","affiliation":[{"name":"Department of Anesthesia and Intensive Care Kuopio University Hospital Kuopio Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,2,22]]},"reference":[{"issue":"2","key":"e_1_2_9_2_1","first-page":"688","article-title":"Comparison of pharmacological activities of buprenorphine and norbuprenorphine: norbuprenorphine is a potent opioid agonist","volume":"297","author":"Huang P","year":"2001","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/00008877-200211000-00005"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0196-9781(00)00252-7"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3723-08.2009"},{"key":"e_1_2_9_6_1","unstructured":"Clarke\u2019s Analysis of Drugs and Poisons: Buprenorphine.https:\/\/www.medicinescomplete.com\/#\/content\/clarke\/c\u2010d1e168521?hspl=buprenorphine. Published 2019. Accessed March 10 2020."},{"issue":"5","key":"e_1_2_9_7_1","first-page":"577","article-title":"The metabolism and excretion of buprenorphine in humans","volume":"12","author":"Cone EJ","year":"1984","journal-title":"Drug Metab Dispos"},{"key":"e_1_2_9_8_1","unstructured":"Electronic Medicines Compendium (EMC).SmPC Temgesic Injection.https:\/\/www.medicines.org.uk\/emc\/product\/1141\/smpc#gref. Published 2016. 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