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

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


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Analgesics, Opioid / metabolism*
  • Biotransformation
  • Carboxylic Ester Hydrolases / metabolism*
  • Chromatography, High Pressure Liquid
  • Dextropropoxyphene / metabolism
  • Enzyme Inhibitors / pharmacology
  • Gas Chromatography-Mass Spectrometry
  • Half-Life
  • Humans
  • Hydrolysis
  • In Vitro Techniques
  • Isoenzymes / metabolism
  • Kinetics
  • Liver / enzymology
  • Liver / metabolism*
  • Meperidine / metabolism*


  • Analgesics, Opioid
  • Enzyme Inhibitors
  • Isoenzymes
  • Meperidine
  • Carboxylic Ester Hydrolases
  • Dextropropoxyphene