Pharmacokinetic studies of acute oral doses of d,1-methadone (25 mg kg('-1)) were carried out on adult non-pregnant, pregnant and lactating female guinea pigs, quantitating the blood plasma methadone levels by gas-liquid chromatography following solvent extraction. The mean (beta) t(, 1/2) of methadone in these animals were 7.7 h, 14.6 h and 11.6 h, respectively. Differences in plasma t(, 1/2) were attributable to difference in drug metabolism. Repeated administration of methadone neither significantly altered the (beta) t(, 1/2) nor had any significant influence on the in vitro hepatic microsomal monooxygenases (nitroanisole O-demethylase (OD) and aniline hydroxylase (AH)). In contrast, methadone treatment markedly reduced the hepatic microsomal glucuronosyltransferase (GT) activity in adult and in perinatal animals. / Methadone (25 mg kg('-1) every 12 h for 2 days) administered to pregnant (60-65 days of gestation) or nursing (0 to 8 days of post-partum) dams resulted in the acquisition of higher tissue levels of the drug in pups by transplacental passage than that obtained via the milk. The pattern distribution of methadone in the pup was different from that observed in the dam, exceedingly high levels of methadone being found in the brain of the perinatal individual.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.68578 |
| Date | January 1980 |
| Creators | Pak, Raphael C. K. |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Department of Pharmacology and Therapeutics) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 000092294, proquestno: AAINK52066, Theses scanned by UMI/ProQuest. |
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