Pharmacokinetics and dose proportionality of domperidone in healthy volunteers.

Domperidone is a potent gastrokinetic agent and antinauseant currently undergoing clinical trials in the United States. The bioequivalence of 20 mg of domperidone given as free-base tablets and maleate salt tablets, and the bioavailability of base and maleate tablets relative to a solution, were studied in 21 fasting men using a crossover design. Plasma samples collected for up to 48 hours were analyzed for domperidone levels, using a sensitive and specific radioimmunoassay (RIA). The absorption of domperidone was very rapid, with mean peak plasma concentration (Cmax) values of 18.8, 15.0, and 20.7 ng/mL attained at 0.9, 1.2, and 0.6 hours after the administration of base tablet, maleate tablet, and solution, respectively. The mean elimination half-life (t1/2) ranged from 12.6 to 16.0 hours. The mean oral clearance (CL/F) after the solution dose was 4,735 +/- 2,017 mL/min and the mean apparent volume of distribution (Vd/F) was 6,272 +/- 5,100 L, indicating an extensive distribution of domperidone in the body. The area under the plasma concentration-time curve (AUC) data demonstrated bioequivalence of base and maleate tablets. The relative bioavailability for base tablet and maleate tablet was 107 +/- 50% and 116 +/- 47%, respectively, of that of the solution. Dose proportionality of domperidone was also studied in 12 subjects at solution doses of 10, 20, and 40 mg. Linear correlations between the dose and Cmax and AUC values were observed. Mean CL/F remained relatively constant after doses of 10, 20, and 40 mg (5,255 +/- 3,159, 4,842 +/- 1,774, and 4,380 +/- 1,289 mL/min, respectively), indicating linear pharmacokinetics of domperidone over the dose range studied.