Trans-stilbene oxide administration increased hepatic glucuronidation of morphine but decreased biliary excretion of morphine glucuronide in rats

Journal Article · Wed Sep 01 04:00:00 EDT 1982 · J. Pharmacol. Exp. Ther.; (United States)

OSTI ID:6657521

Fuhrman-Lane, C; Fujimoto, J M

The effect of the inducing agent trans-stilbene oxide (TSO) on the metabolism and biliary excretion of (/sup 14/C)morphine was studied in the isolated in situ perfused rat liver. After administration of morphine by intraportal injection or by the segmented retrograde intrabiliary injection technique, the TSO-treated group showed a marked decrease in the biliary recovery of morphine as its glucuronide conjugate (morphine-3-glucuronide (MG)). However, recovery of MG in the venous outflow of the single pass perfusate was greatly increased. These findings suggested that TSO treatment enhanced the formation of MG from morphine and changed the primary route of hepatic elimination of MG. TSO treatment also decreased the excretion of morphine (as MG) in the bile of anesthetized renal-ligated rats. This decreased biliary function required several days to develop and appeared closely associated with the inductive effect of TSO. After i.v. administration of (/sup 14/C)MG itself, biliary recovery was also markedly decreased in TSO-treated rats. It is postulated that the effect of the TSO treatment led to either a decrease in canalicular transport of MG into bile or an increase in the efficiency of transfer of MG to the blood at the sinusoidal side of the hepatocyte. Regardless of the mechanism, the results indicate the need to study compartmentalization of drug transport and metabolism functions.

• Research Organization: Toxicology Laboratory, Research Service, Veterans Administration Center, Wood, Wisconsin
• OSTI ID: 6657521
• Journal Information: J. Pharmacol. Exp. Ther.; (United States), Journal Name: J. Pharmacol. Exp. Ther.; (United States) Vol. 222:3; ISSN JPETA
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
ALDEHYDES
ALKALOIDS
ANALGESICS
ANIMALS
BIOLOGICAL PATHWAYS
BODY
CARBON 14 COMPOUNDS
CARBOXYLIC ACIDS
CENTRAL NERVOUS SYSTEM DEPRESSANTS
CHALCOGENIDES
CLEARANCE
DIGESTIVE SYSTEM
DRUGS
EXCRETION
GLANDS
GLUCURONIC ACID
HYDROXY ACIDS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LIVER
MAMMALS
METABOLISM
MORPHINE
NARCOTICS
OPIUM
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
OXIDES
OXYGEN COMPOUNDS
PHARMACOLOGY
RATS
RESPONSE MODIFYING FACTORS
RODENTS
VERTEBRATES