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

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.