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A pharmacokinetic and pharmacodynamic interaction study between nebivolol and the H 2 ‐receptor antagonists cimetidine and ranitidine
Author(s) -
Kamali F.,
Howes A.,
Thomas S. H. L.,
Ford G. A.,
Snoeck E.
Publication year - 1997
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1046/j.1365-2125.1997.54212.x
Subject(s) - nebivolol , cimetidine , ranitidine , pharmacology , pharmacokinetics , pharmacodynamics , placebo , drug interaction , chemistry , medicine , blood pressure , alternative medicine , pathology
Aims The study was designed to investigate the effects of the H 2 ‐receptor antagonists, cimetidine and ranitidine on the pharmacokinetics and pharmacodynamics of nebivolol in healthy volunteers. Methods Twelve healthy volunteers took part in a randomized placebo‐controlled cross‐over study. Each subject received on three separate occasions placebo, cimetidine (400 mg twice daily) or ranitidine (150 mg twice daily) for 24 h before and 48 h after a single oral dose of nebivolol (5 mg). Nebivolol and its individual (+) and (−) enantiomers were determined tby h.p.l.c. Results Ranitidine had no significant effect on nebivolol pharmacokinetics. Cimetidine, however, resulted in a 21–23% increase in C max of unchanged nebivolol and of each enantiomer plus its hydroxylated metabolites. Cimetidine significantly ( P <0.05) increased the AUC [mean±s.d. (95% C.I. of differences in mean)] for unchanged (±)‐nebivolol [7.76±3.07 ng ml −1 h with placebo; 11.50±5.40 (1.75, 8.76) ng ml −1 h with cimetidine], (+)‐nebivolol plus its hydroxylated metabolites [73.0±18.0 ng ml −1 h with placebo; 91.5±25.7 (1.0, 23.1) ng ml −1 h with cimetidine] and (−)‐nebivolol plus its hydroxylated metabolites [101±32 ng ml −1 h with placebo; 123±38 (3.3, 27.0) ng ml −1 h with cimetidine]. Statistical analysis of the resting blood pressure and heart rate and exercise data did not suggest any consistent effects of ranitidine or cimetidine upon the pharmacodynamic effects of nebivolol. Conclusions There was no interaction between ranitidine and nebivolol. Although cimetidine inhibited nebivolol metabolism, it did not have a significant influence on the pharmacodynamics of the drug.