AUTHOR=Chen Rui , Zheng Xin , Hu Pei TITLE=CYP2D6 Phenotyping Using Urine, Plasma, and Saliva Metabolic Ratios to Assess the Impact of CYP2D6∗10 on Interindividual Variation in a Chinese Population JOURNAL=Frontiers in Pharmacology VOLUME=8 YEAR=2017 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2017.00239 DOI=10.3389/fphar.2017.00239 ISSN=1663-9812 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.