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Purpose:  Asian populations have around 40–60% frequency of reduced function allele  CYP2D6 ∗ 10  compared to 1–2% in Caucasian populations. The wide range of  CYP2D6  enzyme activities in subjects with the  CYP2D6 ∗ 10  variant is a big concern for clinical practice. The quantitative analysis measuring the impact of  CYP2D6  enzyme activity as a result of one  CYP2D6 ∗ 10  allele or two  CYP2D6 ∗ 10  alleles has not been reported in large Asian populations.   Methods:  A total of 421 healthy Chinese subjects were genotyped for  CYP2D6  by polymerase chain reaction and direct DNA sequencing. A total of 235 subjects with  CYP2D6 ∗ 1/ ∗ 1  ( n  = 22),  CYP2D6 ∗ 1/ ∗ 10  ( n  = 93),  CYP2D6 ∗ 10/ ∗ 10  ( n  = 85), and  CYP2D6 ∗ 5/ ∗ 10  ( n  = 35) were phenotyped for  CYP2D6  using dextromethorphan as the probe drug. Metabolic ratios (MR) were calculated as the ratio of parent drug to metabolite in 0–3 h urine, 3 h plasma, and 3 h saliva for each sample type.   Results:  The urinary, plasma, or salivary MRs increased successively in subjects with  CYP2D6 ∗ 1/ ∗ 1 ,   ∗ 1/ ∗ 10 ,   ∗ 10/ ∗ 10 , and   ∗ 5/ ∗ 10  (all  P  < 0.001). In the normal metabolizer group, homozygous  CYP2D6 ∗ 10/ ∗ 10  decreased the  CYP2D6  enzyme activity further than heterozygous  CYP2D6 ∗ 1/ ∗ 10 . Urinary, plasma, and salivary MRs were highly correlated.   Conclusion:  The normal metabolizer group calls for a more detailed classification. The activity score system could more accurately predict enzyme activity than by grouping a number of genotypes into a single phenotype group. Single-point plasma samples and saliva samples could be used as alternative phenotyping methods for clinical convenience.

frontiers in pharmacology

CYP2D6 Phenotyping Using Urine, Plasma, and Saliva Metabolic Ratios to Assess the Impact of CYP2D6∗10 on Interindividual Variation in a Chinese Population