Premium
The interaction between H2‐receptor antagonists and beta‐adrenoceptor blockers.
Author(s) -
Mutschler E,
Spahn H,
Kirch W
Publication year - 1984
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 - 10.1111/j.1365-2125.1984.tb02428.x
Subject(s) - cimetidine , atenolol , pindolol , metoprolol , pharmacology , propranolol , drug interaction , ranitidine , chemistry , pharmacokinetics , glucuronide , medicine , endocrinology , metabolite , blood pressure
The degrees of interactions between the H2‐receptor antagonists, cimetidine and ranitidine, and several beta‐adrenoceptor blockers were investigated in healthy volunteers following 7 days of oral monotherapy with penbutolol, propranolol, metoprolol, pindolol and atenolol, and after co‐administration with each of the H2‐receptor antagonists. The kinetic parameters of unmetabolised penbutolol and penbutolol glucuronide were unaffected, whereas the levels of 4‐hydroxypenbutolol and 4‐hydroxypenbutolol glucuronide were significantly reduced. Furthermore, cimetidine led to a marked increase in propranolol and metoprolol plasma levels. During co‐administration with cimetidine, pindolol plasma levels were only slightly raised, whereas the pharmacokinetics of atenolol were not affected. With regard to pharmacodynamics, the inhibition of exercise‐induced tachycardia by each of the beta‐adrenoceptor blockers was not affected by cimetidine. Ranitidine did not alter atenolol plasma levels, but did raise the peak plasma concentration of metoprolol by about 30%. It is concluded that cimetidine interactions do occur and can be predicted for substances metabolised by the cytochrome P‐450 pathway.