The racemic metoprolol H2-antagonist interaction.

The effects of concomitant administration of cimetidine and ranitidine on the pharmacokinetics and pharmacodynamics of multiple-dose metoprolol were investigated in 12 normal, healthy male volunteers. The pharmacokinetics of metoprolol were assessed in terms of racemic metoprolol and the individual (R)- and (S)-enantiomers with a stereoselective assay. Ranitidine had no effect on the pharmacodynamics or pharmacokinetics of metoprolol. Although not affecting the pharmacodynamics of metoprolol, cimetidine did produce an increase in the bioavailability of metoprolol through inhibition of enzymes responsible for the first-pass elimination of the beta-blocker. The effect was stereoselective, with the major effect being on the less pharmacologically active (R)-enantiomer.