The effect of antacid, metoclopramide, and propantheline on the bioavailability of metoprolol and atenolol.

Concomitant administration of antacid increased the maximum concentration (Cpmax) and the area under the plasma concentration-time curve (AUC) of 100 mg oral dose of metoprolol by 25 per cent (p less than 0.05) and 11 per cent (p less than 0.1) respectively. For atenolol the opposite effect was observed and Cpmax and AUC were decreased by 37 and 33 per cent respectively (p less than 0.02). In both cases the antacid did not affect the time-course of atenolol in the plasma or its bioavailability. Propantheline prolonged the absorption phase of atenolol and the time of peaking (tmax) was shifted from 2.1 to 4.5 h. Cpmax of atenolol was essentially unchanged by propantheline pretreatment while the AUC was increased by 36 per cent. It is concluded that the negative effect of the antacid on the bioavailability of atenolol is caused by a reduction in the in vivo dissolution rate due to increased gastric pH. The positive effect of propantheline might be due either to more efficient absorption of atenolol in the upper part of the intestine or more extensive dissolution of the drug as a result of prolonged contact with gastric juice or a combination of these factors.