In healthy normal subjects following the administration of labetalol the pharmacological effects were measured and compared with the plasma concentrations achieved. The inhibition of exercise induced tachycardia and inhibition of exercise induced increases in systolic pressure were significantly related to the administered dose of labetalol. Labetalol was rapidly absorbed from the gastrointestinal tract and peak plasma concentrations occurred two hours after oral administration. There was a linear correlation (r = 0.84) between the logarithm of the plasma concentration and the maximum inhibition of exercise tachycardia at two hours. After intravenous administration there was an immediate reduction in systolic and diastolic blood pressure with a concomitant small increase in heart rate. There was a rapid decline in the associated plasma concentration but the pharmacological effects were maintained in excess of two hours. Our findings are consistent with those of others who have studied the relationship between pharmacological events and plasma concentrations after single doses of other adrenoceptor blocking drugs.

Changes in the British Pharmacopoeia dissolution time requirements have necessitated reformulation of warfarin sodium ('Marevan'). The old and new formulations were compared with each other in eight healthy volunteers given a single 15 mg dose of each in a cross-over study and also in 19 patients receiving warfarin therapy. In the volunteer study, a significant but small increase in bioavailability was observed for the new formulation. However, the effects of the two formulations on the prothrombin ratio and on clotting factors II, VII, IX and X were not significantly different. Irrespective of formulation, the greatest changes in factors II, VII and X were observed after the first dose of warfarin. With factor IX, the greatest response was observed after the second dose. The clinical study in patients confirmed that the old and new formulations of Marevan are interchangeable on a dose for dose basis. A sensitive semi-automated warfarin assay technique is described.

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An automated continuous flow liquid-liquid extraction procedure is described for the separation of the H2-antagonist loxtidine from plasma samples containing two metabolites which interfere in the radioimmunoassay of the drug. The extraction of the bronchodilator salbutamol was studied using the DuPont Prep I automated liquid solid extraction apparatus, with a 12 cartridge capacity, and a vacuum extraction box designed in this laboratory to hold 30 Sep-pak C-18 (Waters Associates) cartridges. Twenty-four plasma samples per hour can be automatically processed with the Prep I. Although the vacuum box is not fully automated 45 plasma samples per hour can be processed. The Prep I can only be used with DuPont XAD, strong cation and anion exchange cartridges. Cartridges containing alumina, silica, florisil, cation and anion exchange resins and reverse phase packings can all be used with the vacuum extraction box. The latter costs only a fraction of the Prep I and therefore each analyst can have his own unit.