Labetalol was the first of a new class of antihypertensive drugs with both &agr;- and &bgr;-adrenoceptor blocking properties present in the same molecule. Its efficacy has been confirmed by double-blind studies in the treatment of all grades of hypertension and in angina pectoris. The drug's major dose-related side effect is postural hypotension.The clinical formulation of labetalol consists of equal proportions of 4 optical isomers. One of these (the RR isomer) is probably responsible for the drug's &bgr;-adrenoceptor blockade and another (the SR isomer) produces most of the &agr;-blockade. Most of the presently available pharmacokinetic information concerning labetalol is from studies utilising a fluorimetric assay but this has recently been superceded by more specific high-pressure liquid chromatographic (HPLC) procedures.Labetalol is absorbed rapidly after oral administration with peak plasma concentrations generally being achieved within 2 hours. The bioavailability varies from 10% to over 80% in different subjects. Average bioavailability has been reported to correlate with age, with values of approximately 30% in the 30- to 40-year age group and approximately 65% at 80 years. There is also evidence that the bioavailability increases moderately when the drug is taken with food. About 50% of the drug is bound to protein in the plasma.The apparent volume of distribution at equilibrium varies from approximately 200 to over 800L, suggesting that concentration of labetalol occurs in extravascular sites. Radiochemical analysis in animals has shown high levels of accumulation in the lung, liver and kidney with little present in brain tissue. This is in keeping with the relatively low lipid solubility of labetalol.The half-life of labetalol in plasma is 3 to 3.5 hours. The drug is eliminated mainly by hepatic metabolism with the production of several biologically inactive glucuronides which in turn are excreted in the urine and bile. Approximately 85% of labetalol in the blood is removed during a single passage through the liver; thus, like propranolol, labetalol's clearance is probably flow dependent (i.e. it is sensitive to alterations in hepatic blood flow). Small doses of the drug (i.e. 300mg daily) have been shown to reduce antipyrine clearance by approximately 15%, and further studies are necessary to determine whether high doses produce a greater, possibly clinically significant, inhibition of mixed-function oxidase activity.After both single doses and during long term treatment the plasma concentration-time profile of labetalol shows marked variation between different individuals. A broad relationship exists between the plasma concentration and the fall in blood pressure, particularly in the upright position. However, individual sensitivity to the drug's hypotensive action also plays a major role in determining the response.There is only limited information available concerning the handling of labetalol in pregnancy and in disease states. In newborn infants, plasma labetalol concentrations are 30 to 50% of those of the mother and concentrations in breast milk have been reported to be 22 to 45% of the maternal plasma concentration. In chronic liver disease, bioavailability of the drug is reported to be doubled and plasma concentrations are substantially higher than in normal controls. In chronic renal disease the pharmacokinetic handling is reported to be virtually unaltered.