Extrahepatic glucuronidation of morphine in the dog

E. Jacqz, S. Ward, R. Johnson, S. Schenker, J. Gerkens, R. A. Branch

Research output: Contribution to journalArticlepeer-review

55 Scopus citations

Abstract

The pharmacokinetic disposition of morphine was studied in sham-operated dogs, dogs with hepatic devascularization, and dogs with bile duct and ureter ligation afer iv administration of 1 mg/kg of morphine. In sham-operated dogs, morphine is rapidly distributed and eliminated, with a terminal half-life of 65 ± 30 min. Morphine glucuronide appeared in plasma within 5 min and rose rapidly to levels an order of magnitude higher than morphine levels, before both declined in parallel. In hepatic devascularized dogs, there was a marked delay in morphine elimination due to a 47% reduction in clearance. The appearance of morphine glucuronide in plasma was not delayed, but the AUC of morphine glucuronide was reduced by 56% compared to control for the first 180 min. In bile duct- and ureter-ligated dogs, elimination of morphine was increased and morphine glucuronide elimination from plasma was decreased, suggesting that glucuronide normally excreted in bile is hydrolyzed back to the parent compound and reabsorbed in sham-operated control animals. In conclusion, morphine was glucuronidated by both hepatic and extrahepatic glucuronyltransferases to an approximately equal extent in the dog.

Original languageEnglish (US)
Pages (from-to)627-630
Number of pages4
JournalDrug Metabolism and Disposition
Volume14
Issue number6
StatePublished - 1986
Externally publishedYes

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

Fingerprint

Dive into the research topics of 'Extrahepatic glucuronidation of morphine in the dog'. Together they form a unique fingerprint.

Cite this