薬効・安全性評価に及ぼす人種差要因

概要

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Ethnic difference is considered to be a major barrier in world-wide drug development. There seem to be many ethnic factors, genetic, environmental and cultural differences. There exists genetic polymorphism in drug metabolism especially for <I>N</I>-acetylation, debrisoquine hydroxylation and S-mephenytoin hydroxylation. The frequency of slow acetylator, poor metabolizer of debrisoquine and S-mephenytoin are 10 %, less than 1 % and 20 % in Japanese and 50 %, 10 % and 5 % in Caucasians respectively. Clinical responses and adverse effect of drugs are associated with these phenotypes. A retrospective study was conducted to determine whether inter-ethnic pharmacokinetic difference is larger than intra-ethnic variability. Individual pharmacokinetic parameters for most drugs were found to be extremely variable, but similarities of pharmacokinetic parameters were observed for C<SUB>max</SUB>, and AUC between Japanese and other races. The results suggest that intra-ethnic variability is larger than inter-ethnic difference. The knowledge of genetic polymorphisms must find its way into clinical practice in order to achieve rational drug therapy that is more effective and safer for the benefit of the patient.
社団法人日本薬理学会の論文