The non-human primate: a possible model for human genetically determined polymorphisms in oxidative drug metabolism.
The non-human primate: a possible model for human genetically determined polymorphisms in oxidative drug metabolism.
复制标题
非人类灵长类动物：氧化药物代谢中人类遗传决定的多态性的可能模型。
作者：
E. Jacqz;C. Billante;F. Moysan;H. Mathieu
药物氧化的遗传多态性是药物反应和毒性个体间差异的主要决定因素。许多动物模型，包括大鼠，已被用于药物遗传学的临床研究。然而，由于物种间的巨大差异，这些数据很难外推到人类身上。因此，我们对64只非人灵长类动物进行异喹胍和美芬妥英多态性的表型分析，并确定了这两种药物的弱代谢者。异喹胍和美芬妥英的弱代谢者频率分别为14%（95%置信限，6.5-25%）和3%（95%置信限，0.5-10%）。如果家系研究证明两种独立缺陷的遗传基础，则该动物种属可用于体内和体外药物遗传学研究。
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.