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

Kortunay S., Bozkurt A., Basci N. E. , Kayaalp S.

EUROPEAN JOURNAL OF DRUG METABOLISM AND PHARMACOKINETICS, vol.27, no.3, pp.171-174, 2002 (Peer-Reviewed Journal) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 27 Issue: 3
  • Publication Date: 2002
  • Doi Number: 10.1007/bf03190453
  • Journal Indexes: Science Citation Index Expanded, Scopus
  • Page Numbers: pp.171-174


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 weekly intervals, followed I It 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.