Pharmacokinetics of labetalol in healthy volunteers.

The pharmacokinetics of labetalol, a combined alpha- and beta-receptor blocking agent, were studied in eight healthy volunteers. After intravenous injections (n = 4) of 1.5 mg/kg, the drug was rapidly distributed (mean T 1/2 = 4.9 min) and quite rapidly eliminated (mean T 1/2 = 4.9 hrs). The mean total plasma clearance value was 24.80 ml/min/kg. The values for Vdc (mean 1.1 l/kg) and Vdss (mean 9.41 l/kg) indicate extensive extravascular distribution of labetalol. The systemic availability was about 18%. There was a significant correlation between the calculated drug concentrations in the hypothetical compartment 2 and the percentage decreases in blood pressure after the intravenous injection. After a single 200 mg oral dose (solution, non-coated and coated tablets), the tablet formulation had no significant effect on the gastrointestinal absorption. After repeated oral doses of 200 mg twice daily (n = 4), no accumulation in plasma was observed.