The Influence of Two Histamine H2-Receptor Antagonists, Cimetidine and Ranitidine, on the Plasma Levels and Clinical Effect of Nifedipine and Metoprolol

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Abstract
In six healthy volunteers pharmacokinetic and pharmacodynamic interaction of metoprolol and nifedipine with Cimetidine and ranitidine was investigated after 1 week of monotherapy with nifedipine and metoprolol and after 1 week each of combined treatment of these drugs with the H2-receptor antagonists. Ranitidine led to a 50% increase in mean peak plasma levels and in the area under the plasma level time curve (AUC) of metoprolol (p < 0.05) and to an insignificant 30% rise in these parameters of nifedipine (p > 0.05). Cimetidine increased metoprolol’s peak plasma levels of AUC by about 60% (p < 0.05) and those of nifedipine by 80% (p < 0.05). Compared to monotherapy with metoprolol beta blocking activity measured by exercise induced tachycardia was not significantly stronger inhibited under the combined treatment of metoprolol with each of the two H2-receptor antagonists. On the other hand the antihypertensive effect of nifedipine was significantly increased during concurrent administration of Cimetidine in seven hypertensive patients when compared with monotherapy. Thus pharmacokinetic interaction between Cimetidine and nifedipine leads to a clinically relevant pharmacodynamic interference.

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