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 < 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 < 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 < 0.01) in blood pressure with pretreatment levels (163/108), reaching a minimum at 5 hr (133/89). During long‐term therapy incremental 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. Clinical Pharmacology and Therapeutics (1980) 27 , 756–762; doi: 10.1038/clpt.1980.106