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

Autor: Atila Bozkurt, S. Oguz Kayaalp, Nursabah E. Basci, Selim Kortunay
Rok vydání: 2002
Předmět:
Zdroj: European journal of drug metabolism and pharmacokinetics. 27(3)
ISSN: 0378-7966
Popis: 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 metabolisers. The volunteers took increasing single oral doses of one of the two antihistaminic drugs in randomized order, at weeklyy intervals, followed 1 h later by debrisoquine test. Terfenadine and diphhenhydramine 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.
Databáze: OpenAIRE
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