Clinical inhibition of CYP2D6‐catalysed metabolism by the antianginal agent perhexiline

Aims Perhexiline is an antianginal agent that displays both saturable and polymorphic metabolism via CYP2D6. The aim of this study was to determine whether perhexiline produces clinically significant inhibition of CYP2D6‐catalysed metabolism in angina patients. Methods The effects of perhexiline on CYP2D6‐catalysed metabolism were investigated by comparing urinary total dextrorphan/dextromethorphan metabolic ratios following a single dose of dextromethorphan (16.4 mg) in eight matched control patients not taking perhexiline and 24 patients taking perhexiline. All of the patients taking perhexiline had blood drawn for CYP2D6 genotyping as well as to measure plasma perhexiline and cis‐OH‐perhexiline concentrations. Results Median (range) dextrorphan/dextromethorphan metabolic ratios were significantly higher (P