Determination of dextromethorphan metabolic phenotype by salivary analysis with a reference to genotype in Chinese patients receiving renal hemodialysis

Clinical Pharmacology and Therapeutics
Z Y HouR L Woosley

Abstract

The polymorphic metabolism of debrisoquin and sparteine by cytochrome P450IID6 (CYP2D6) is genetically determined. Determination of the CYP2D6 metabolic phenotype with conventional urine analytic methods is not feasible in anuric patients with renal failure. The possibility of using salivary analysis, with dextromethorphan as a probe drug, to determine the CYP2D6 metabolic phenotype in patients with renal failure was evaluated. One hundred four Chinese patients with renal failure were recruited. All 104 patients were receiving hemodialysis. Saliva was collected before and at 3 hours after each patient took a capsule of dextromethorphan hydrobromide (30 mg). Four patients were excluded because of insufficient samples of saliva. The distribution of logarithms of the metabolic ratios (log[MR]) in the 100 patients appeared to be normal. Administration of quinidine sulfate (200 mg twice daily) to nine of the patients significantly and markedly increased the dextromethorphan metabolic ratios. The metabolic ratios of nine patients pretreated with quinidine were higher than any of the 100 patients with renal failure who did not receive quinidine pretreatment. A metabolic ratio of 33 separated these two groups. Genomic deoxyribonucleic ...Continue Reading

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Citations

Mar 27, 2001·Annual Review of Pharmacology and Toxicology·H G XieC M Stein
Feb 3, 2007·European Journal of Clinical Pharmacology·D FrankU Fuhr
Aug 5, 2015·Clinical Pharmacokinetics·Pieter M M De KeselChristophe P Stove
Apr 12, 2005·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Silvana BorgesJ Christopher Gorski
Aug 21, 2003·Journal of Biomedical Science·Geng-Chang YehMing-Thau Sheu
Jun 21, 2019·Bioanalysis·Karine Souza SebaRita de Cássia Elias Estrela

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