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

Asian populations have around 40-60% frequency of reduced function allele compared to 1-2% in Caucasian populations. The wide range of enzyme activities in subjects with the variant is a big concern for clinical practice. The quantitative analysis measuring the impact of enzyme activity as a result of one allele or two alleles has not been reported in large Asian populations. A total of 421 healthy Chinese subjects were genotyped for by polymerase chain reaction and direct DNA sequencing. A total of 235 subjects with ( = 22), ( = 93), ( = 85), and ( = 35) were phenotyped for 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. The urinary, plasma, or salivary MRs increased successively in subjects with , , , and (all < 0.001). In the normal metabolizer group, homozygous decreased the enzyme activity further than heterozygous . Urinary, plasma, and salivary MRs were highly correlated. 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.