Metoprolol kinetics and dose response in hypertensive patients

The kinetics and dose-response characteristics of metoprolol were examined in a series of hypertensive patients. In 14 the elimination half-life of metoprolol after single 100-mg doses (4.1 +/- 0.6 hr) was prolonged (p less than 0.05) after 6 to 12 wk of therapy (5.6 +/- 0.7 hr). In 5 patients receiving 100 mg twice daily evidence of nonlinear metoprolol kinetics emerged, because the area under the concentration-time curve at steady state was 86.8% more (p less than 0.02) than predicted from a single dose. Kinetic data from single doses of metoprolol appear to be a poor predictor of steady-state kinetics. Single metoprolol dosage also induced a fall (p less than 0.01) in blood pressure with pretreatment levels (163/108), reaching a minimum at 5 hr (133/189). During long-term therapy incremented doses of metoprolol between 100 and 600 mg/day in 34 hypertensive patients resulted in a relatively horizontal dose-response curve at doses above 200 mg/day.