The effects of ranitidine and cimetidine on the pharmacokinetics and pharmacodynamics of metoprolol

Abstract

SUMMARY The impact of cimetidine, ranitidine and placebo on the pharmacokinetics of metoprolol, given either as a single dose (100 mg) or for 7 days (100 mg b.d.), has been evaluated in two separate studies. The doses used were 800 mg cimetidine daily and 300 mg ranitidine daily. The subjects were all young, healthy volunteers. In the single dose study, cimetidine produced a marked increase in the peak plasma concentration of metoprolol and in the area under the plasma concentration‐time curve; ranitidine had less effect, though the area under the curve was significantly greater than placebo. In the chronic dosing study, the area under the curve for metoprolol was also significantly higher on cimetidine (1796 ng h/ml; P < 0.001) whereas the area under the curve on ranitidine (1258 ng h/ml) was comparable to that on placebo (1183 ng h/ml). Despite these drug‐induced changes in plasma metoprolol concentration, neither cimetidine nor ranitidine altered the change in exercise‐induced heart rate during dosing with metoprolol.

Development and validation of an HPLC‐UV method for the simultaneous determination of the antipsychotics clozapine, olanzapine and quetiapine, several beta‐blockers and their metabolites

“…Inhibition of these isoenzymes slows down the metabolism of the drugs, eventually resulting in increased serum concentrations and increased risk of side effects. Altered serum concentrations and increased occurrence of adverse effects caused by the CYP2D6 inhibitors cimetidine and quinidine are described for MET (Chellingsworth, Laugher, Akhlaghi, Jack, & Kendall, ; Kirch, Spahn, Kohler, Ohnhaus, & Mutschler, ; Leemann, Devi, & Dayer, ; Mutschler, Spahn, & Kirch, ; Toon et al . , ), PRO (Kirch et al .…”