title: Effects of terfenadine and diphenhydramine on the CYP2D6 activity in healthy volunteers.
abstract: The aim of this study was to investigate the effects of two antihistaminic drugs, terfenadine and diphenhydramine on CYP2D6 activity by using debrisoquine as a model substrate. The study was carried out as an in vivo single-dose study in 12 young, healthy men. All volunteers had previously been identified as debrisoquine-extensive metabolizers. The volunteers took increasing single oral doses of one of the two antihistaminic drugs in randomized order, at weekly intervals, followed 1 h later by debrisoquine test. Terfenadine and diphenhydramine were given in the doses of 60 and 120 mg; 100 and 150 mg, respectively. The 8-hr urinary concentrations of debrisoquine and 4-hydroxydebrisoquine were determined by high-performance liquid chromatography (HPLC). With increasing doses of terfenadine and diphenhydramine, there was no statistically significant increase in the debrisoquine metabolic ratios (P > 0.05, Page's test for trend). The difference between the median debrisoquine metabolic ratios before and after treatments with terfenadine or diphenhydramine were not statistically significant (Wilcoxon's test). This investigation indicates that single-dose administration of diphenhydramine or terfenadine has no effect on the CYP2D6-mediated hydroxylation of debrisoquine in healthy volunteers.
mesh_terms: D000328:Adult; D019389:Cytochrome P-450 CYP2D6 / Q000378:metabolism*; D003647:Debrisoquin / Q000652:urine; D004155:Diphenhydramine / Q000494:pharmacology*; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006801:Humans; D008297:Male; D018709:Statistics, Nonparametric; D016593:Terfenadine / Q000494:pharmacology*
chemical_list: D006634:Histamine H1 Antagonists; D016593:Terfenadine; D004155:Diphenhydramine; D019389:Cytochrome P-450 CYP2D6; D003647:Debrisoquin