TY - JOUR T1 - Binding and Hydrolysis of Meperidine by Human Liver Carboxylesterase hCE-1 JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 314 LP - 318 VL - 290 IS - 1 AU - Jing Zhang AU - Joe C. Burnell AU - Natividad Dumaual AU - William F. Bosron Y1 - 1999/07/01 UR - http://jpet.aspetjournals.org/content/290/1/314.abstract N2 - 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, withKi 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. The American Society for Pharmacology and Experimental Therapeutics ER -