Comparison of human and rhesus monkey in vitro phase I and phase II hepatic drug metabolism activities.
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.[1]References
- Comparison of human and rhesus monkey in vitro phase I and phase II hepatic drug metabolism activities. Stevens, J.C., Shipley, L.A., Cashman, J.R., Vandenbranden, M., Wrighton, S.A. Drug Metab. Dispos. (1993) [Pubmed]
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