抄録
The CYP2D subfamily has received much attention during the past decade due largely to the involvement of CYP2D6 in human, particularly as the enzyme metabolizes over 50 clinically important drugs. More than 40 genetic polymorphisms exist in human CYP2D6. The frequency of the poor metabolizer (PM) with deficient CYP2D6 activity is reported to be 5% to 10% in Caucasians and less than 1% in Japanese. The CYP2D6*10 allele, which includes both the CYP2D6*10A and CYP2D6*10B variants, is widely observed in Japanese (38%; our data) and Chinese (50%), and has two amino acid changes Pro34→Ser and Ser486→Thr.
We have found a significant influence on the pharmacokinetics of venlafaxine by CYP2D6*10 allele in a Japanese population, and have emphasized a clinical significance of CYP2D6*10 allele in addition to PM-related alleles in a Japanese population. Recently, several studies on the relationship between CYP2D6*10 and pharmacokinetic of CYP2D6 substrates have reported. We have also expressed CYP2D6.10 using yeast expression systems to determine its metabolic specificity.
In this review, we introduce our findings in vivo and in vitro on CYP2D6*10 and prospects of its clinical relevance in the future.
