Binding and hydrolysis of meperidine by human liver carboxylesterase hCE-1.

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Zhang J, Burnell JC, Dumaual N, Bosron WF

Binding and hydrolysis of meperidine by human liver carboxylesterase hCE-1.

J Pharmacol Exp Ther. 1999 Jul;290(1):314-8.

PubMed ID
10381793 [ View in PubMed
]
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.

DrugBank Data that Cites this Article

Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
DextropropoxypheneLiver carboxylesterase 1ProteinHumans
Unknown
Not AvailableDetails
MeperidineLiver carboxylesterase 1ProteinHumans
Unknown
Not AvailableDetails