The interaction between H2-receptor antagonists and beta-adrenoceptor blockers.
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.
D000319:Adrenergic beta-Antagonists / Q000378:metabolism / Q000494:pharmacology*; D001262:Atenolol / Q000494:pharmacology; D002927:Cimetidine / Q000494:pharmacology; D004347:Drug Interactions; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D008790:Metoprolol / Q000494:pharmacology; D010394:Penbutolol / Q000494:pharmacology; D010869:Pindolol / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011899:Ranitidine / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D006635:Histamine H2 Antagonists; D001262:Atenolol; D010394:Penbutolol; D002927:Cimetidine; D011899:Ranitidine; D011433:Propranolol; D010869:Pindolol; D008790:Metoprolol