The non-human primate: a possible model for human genetically determined polymorphisms in oxidative drug metabolism.
Genetic polymorphisms of drug oxidation are major determinants of interindividual variations in drug response and toxicity. Many animal models, including rats, have been used for clinical investigations of pharmacogenetics. However, because of large interspecies differences, these data are difficult to extrapolate to humans. We therefore phenotyped 64 non-human primates for debrisoquine and mephenytoin polymorphisms and identified poor metabolizers of both drugs. The frequency of poor metabolizers was 14% for debrisoquine (95% confidence limits, 6.5-25%) and 3% for mephenytoin (95% confidence limits, 0.5-10%). If family studies demonstrate a genetic basis for the two independent defects, this animal species could be used for in vivo and in vitro pharmacogenetic investigations.
Jacqz
E
E
INSERM U.120, Le Vésinet, France.
Billante
C
C
Moysan
F
F
Mathieu
H
H
D000818:Animals; D001711:Biotransformation; D003647:Debrisoquin / Q000378:metabolism*; D005260:Female; D006827:Hydantoins / Q000378:metabolism*; D007546:Isoquinolines / Q000378:metabolism*; D008251:Macaca / Q000378:metabolism*; D008252:Macaca fascicularis / Q000378:metabolism*; D008297:Male; D008617:Mephenytoin / Q000378:metabolism*; D010084:Oxidation-Reduction; D011110:Polymorphism, Genetic
D006827:Hydantoins; D007546:Isoquinolines; D008617:Mephenytoin; D003647:Debrisoquin