Comparison in young and elderly patients of pharmacodynamics and disposition of labetalol in systemic hypertension

Abstract

Pharmacodynamics and pharmacokinetics of labetalol, a combined α- and β-adrenoceptor antagonist drug, were studied in elderly and young hypertensive patients. After receiving intravenous labetalol, elderly patients had a greater maximal mean decrease in systolic blood pressure (BP) (39 ± 8 vs 25 ± 13 mm Hg, p < 0.02); however, maximal decrease in diastolic BP was similar in elderly (18 ± 10 mm Hg) and young (17 ± 6 mm Hg) patients. After receiving oral labetalol, elderly patients had a greater maximal decrease in standing systolic BP (41 ± 16 vs 16 ± 14 mm Hg, p < 0.001) and similar decreases in standing diastolic BP (21 ± 7 vs 17 ± 9 mm Hg). Sitting maximal BP decreases after oral labetalol treatment were similar in elderly and young patients (12 ± 16 vs 17 ± 7 mm Hg systolic and 24 ± 6 vs 12 ± 7 diastolic). The decrease in heart rate was greater in young patients after intravenous labetalol administration. To evaluate labetalol Pharmacodynamics, a linear model was used. Slope of labetalol concentration vs systolic BP for elderly vs young patients was 0.928 ± 1.05 vs 0.326 ± 0.490 ng/ml · mm Hg −1 (difference not significant). The slope of labetalol concentration vs heart rate for elderly vs young patients was 0.176 ± 0.063 vs 0.406 ± 0.303 ng/ml · beats/min −1 (p < 0.05), with 2 elderly patients showing no decrease in heart rate. Labetalol intravenous elimination half-life was markedly prolonged in the elderly (8.5 ± 4.1 vs 2.9 ±1.3 hours, p < 0.001) because of a decrease in total clearance (13.9 ± 6.4 vs 19.4 ± 6.2 ml/min/kg, p < 0.05). After oral labetalol administration, peak concentration was greater in elderly patients (214 ± 123 vs 109 ± 60 ng/ml, p < 0.05). Labetalol absolute bioavailability was not signficantly different between elderly and young patients (19.6 ± 9.6 vs 14.5 ±10.3%). The combination of increased antihypertensive effect and decreased clearance suggest that smaller labetalol doses may be required in elderly hypertensive persons to achieve antihypertensive effects comparable to those in young hypertensive persons.