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.

Adult↗

PubMedDate not supplied

Plasma concentrations and beta-blocking effects in normal volunteers after intravenous doses of metoprolol and propranolol.

The pharmacokinetics of metoprolol and propranolol in 6 healthy volunteers were compared after an intravenous dose of 10 mg of each drug. The mean t1/2, beta was 3.6 hr for both drugs, but due to a larger volume of distribution, the total body clearance was significantly higher for metoprolol (1.20 liters/min) than for propranolol (0.81 liters/min). The individual pharmacokinetic data were used to calculate the doses required to increase the amount of each drug in the body to 10 and 20 mg at 90 and 180 min respectively after an initial intravenous dose of 5.0 mg. The effect on exercise heart rate was determined 30 min after each dose. After identical doses, the two drugs had similar beta-blocking effects in terms of reducing exercise-induced tachycardia. These effects increased with the dose administered. The plasma levels of propranolol were twice as high as those of metoprolol for identical degrees of beta-blockade. The slope of the regression line for the relationship between the beta-blocking effect and log plasma concentrations was the same for the two drugs.

Adrenergic beta-Antagonists↗

PubMedDate not supplied

Re-evaluation of the antimineralocorticoid effect of the spironolactone metabolite, canrenone, from plasma concentrations determined by a new high-pressure liquid-chromatographic method.

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Adult↗