TY - JOUR T1 - Comparison of human and rhesus monkey in vitro phase I and phase II hepatic drug metabolism activities. JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 753 LP - 760 VL - 21 IS - 5 AU - J C Stevens AU - L A Shipley AU - J R Cashman AU - M Vandenbranden AU - S A Wrighton Y1 - 1993/09/01 UR - http://dmd.aspetjournals.org/content/21/5/753.abstract N2 - Twelve human and six rhesus monkey liver samples were analyzed in vitro for phase I metabolism and phase II conjugation activity. Of the eight P-450-dependent activities measured, only N-nitrosodimethylamine N-demethylase activity was not significantly different between the two species. Coumarin 7-hydroxylase activity was greater in the human as compared with the rhesus monkey samples, whereas erythromycin N-demethylase, benzphetamine N-demethylase, pentoxyresorufin O-dealkylase, ethoxycoumarin O-deethylase, and ethoxyresorufin O-deethylase activities were significantly greater in rhesus monkey microsome samples (p < or = 0.01). Cimetidine S-oxygenation and chlorpromazine N-oxygenation were 2.1- and 2.6-fold higher in rhesus monkey samples. Of the seven microsomal and cytosolic phase II activities measured, only 17 alpha-ethynylestradiol glucuronidation was significantly higher in the human samples. The genetic polymorphism for isoniazid acetylation was evident only in the human samples, with activities varying 200-fold. This study shows that, although the rhesus monkey is often used by the pharmaceutical industry as a representative mammalian species for drug testing, the in vitro metabolic capabilities of the human and rhesus monkey drug metabolizing enzymes are different. ER -