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

ABSTRACT: 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.

SUBMITTER: Chen R 

PROVIDER: S-EPMC5411458 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature