Drug metabolism by the fetal stump-tailed monkey (Macaca arctoides). Hepatic microsomal N-demethylation and glucuronidation as measured by radiometric assays

Abstract

Sensitive radiometric assays were adapted to study the development and kinetics of meperidine and methadone N-demethylation and morphine glucuronidation by microsomes isolated from livers of fetal stump-tailed macaques (Macaca arctoides). Times in development selected for study were midterm, three-quarter term, near term and newborn (0.5 h and 14 days). With appropriate attention to keeping blanks low, hepatic drug metabolism was demonstrable as early as midterm. Vmax for the N-demethylation reactions (nmole product/10 min/mg microsomal protein) increased throughout gestation, whereas the apparent Kms remained constant. With respect to morphine glucuronidation, all kinetic parameters remained constant throughout the last half of gestation.