Effects of terfenadine and diphenhydramine on the CYP2D6 activity in healthy volunteers.

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.