Zhang_1999_J.Pharmacol.Exp.Ther_290_314

Reference

Title : Binding and hydrolysis of meperidine by human liver carboxylesterase hCE-1 - Zhang_1999_J.Pharmacol.Exp.Ther_290_314
Author(s) : Zhang J , Burnell JC , Dumaual N , Bosron WF
Ref : Journal of Pharmacology & Experimental Therapeutics , 290 :314 , 1999
Abstract :

Human liver carboxylesterases catalyze the hydrolysis of apolar drug or xenobiotic esters into more soluble acid and alcohol products for elimination. Two carboxylesterases, hCE-1 and hCE-2, have been purified and characterized with respect to their role in cocaine and heroin hydrolysis. The binding of meperidine (Demerol) and propoxyphene (Darvon) was examined in a competitive binding, spectrophotometric assay. The hCE-1 and hCE-2 bound both drugs, with Ki values in the 0.4- to 1.3-mM range. Meperidine was hydrolyzed to meperidinic acid and ethanol by hCE-1 but not hCE-2. The Km of hCE-1 for meperidine was 1.9 mM and the kcat (catalytic rate constant) was 0.67 min-1. Hydrolysis of meperidine by hCE-1 was consistent with its specificity for hydrolysis of esters containing simple aliphatic alcohol substituents. Hence, hCE-1 in human liver microsomes may play an important role in meperidine elimination. Propoxyphene was not hydrolyzed by hCE-1 or hCE-2. This observation is consistent with the absence of a major hydrolytic pathway for propoxyphene metabolism in humans.

PubMedSearch : Zhang_1999_J.Pharmacol.Exp.Ther_290_314
PubMedID: 10381793

Related information

Inhibitor Meperidine
Substrate Meperidine    Meperidine

Citations formats

Zhang J, Burnell JC, Dumaual N, Bosron WF (1999)
Binding and hydrolysis of meperidine by human liver carboxylesterase hCE-1
Journal of Pharmacology & Experimental Therapeutics 290 :314

Zhang J, Burnell JC, Dumaual N, Bosron WF (1999)
Journal of Pharmacology & Experimental Therapeutics 290 :314