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

Frontiers in Pharmacology
Rui ChenPei Hu

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, ...Continue Reading

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Citations

Sep 19, 2018·Bioanalysis·Santosh Kumar Sreevatsav AdirajuSussan Ghassabian
Jun 6, 2020·Expert Review of Clinical Pharmacology·G Magliocco, Y Daali
Jun 21, 2019·Bioanalysis·Karine Souza SebaRita de Cássia Elias Estrela

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Methods Mentioned

BETA
PCR
urine sample collection

Software Mentioned

CPIC

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