Clinical pharmacology of labetalol.

The clinical pharmacology of labetalol has been evaluated using pharmacological and physiological test methods. Labetalol displaces the log dose-response curves to the right of isoprenaline-induced increases in heart rate, cardiac output and decreases in diastolic BP. The similarity in the displacements of these curves suggests labetalol has non-selective β-adrenoceptor-blocking properties. Labetalol inhibits exercise-induced increases in heart rate and systolic BP, inhibits tilt tachycardia and that associated with Valsalva's manoeuvre. Direct comparison with propranolol using the methods above have shown that the β-adrenoceptor-blocking effect of labetalol is qualitatively similar to that of propranolol but that propranolol is more potent weight for weight to the order of 4 to 6:1 propranolol:labetalol. In respect of their effects on respiratory function, labetalol and propranolol are qualitatively different; whereas propranolol increases airways resistance in equipotent β-adrenoceptor-blocking doses, labetalol does not. Labetalol displaces the log dose-response curves of phenylephrine and noradrenaline-induced increases in systolic and diastolic BPs to the right consistent with an α-adrenoceptor-blocking action. Labetalol inhibits increases in BP due to a cold stimulus, whereas propranolol does not. The combined α- and β-adrenoceptor-blocking effect of labetalol after acute and chronic administration leads to reductions in BP and peripheral resistance but little change in heart rate or cardiac output at rest. During exercise, increases in BP and heart rate are attenuated but cardiac output increases are only significantly diminished at high levels of exercise. Labetalol is less lipophylic than propranolol, with a partition coefficient of 1.2. It is almost completely metabolized being extensively conjugated.