Pharmacogenetic entities extensively studied and showing an interethnic difference in the drug-metabolizing enzyme activity include N-acetyltransferase (NAT2) and cytochromes P450 (CYP) 2C (i.e., CYP2C9 and 19) and CYP2D6. Individuals are classified to rapid and slow acetylators in NAT2 phenotyping or genotyping test, whereas those are classified to extensive and poor metabolizers in CYP-related phenotyping or genotyping test. On a theoretical basis, a drug that is metabolized via a genetically determined enzyme should show an interethnic difference and intraethnic difference in the therapeutic consequences (e.g., therapeutic effectiveness, development of adverse drug reactions) of that drug. However, this theoretical consideration has not been proved, because 1) no prospective parallel study using the same research protocol has been conducted in the different ethnic patient groups; and 2) pharmacogenetic-oriented studies have been conducted within the same ethnic patient groups. I will discuss the given topics on NAT2 and CYP2C subfamily (CYP2C9 and 19) and CYP2D6 in light of the impacts on 1) therapeutic effectiveness ; 2) development of adverse drug reaction(s) ; 3) individualized or optimized drug therapy.

In conclusion, I am tempted to emphasize the ethnic differences in drug-metabolizing enzyme activity to be clinically important for not only inter- and intraethnic patient clinical cares but also drug development process applicable to worldwide humanistic therapeutic benefits.