THE SINGLE AND MULTIPLE-DOSE PHARMACOKINETICS OF PRANLUKAST IN HEALTHY-VOLUNTEERS

Objective: The pharmacokinetics of pranlukast, a leukotriene LTD(4) an tagonist, were studied in 48 young, healthy subjects after single and repeated oral doses (given every 12 h) ranging from 112.5 to 675 mg. T he doses were administered 30 minutes after a light breakfast. Results : Maximal drug concentrations generally occurred between 2 and 6 h aft er dosing, and there was some evidence of an absorption lag-time. Seco ndary peaks were observed in the plasma concentration vs. time profile s of many of the study subjects after both single and repeated doses, particularly during the period of maximum drug absorption. In general, after both single and repeated doses, there were related increases in the corresponding C-max and AUC with a rise in dose, although the inc rease was diminished at doses above 450 mg. With repeated dosing of pr anlukast the mean AUC was generally higher (up to 1.6-fold), and the h igher plasma concentrations allowed characterisation of a longer mean tin than after single dose administration. The mean steady-state troug h plasma concentrations attained after evening doses were considerably higher (up to 14-fold) than those obtained after the morning dose. Co nclusion: The data suggested that the pharmacokinetics of pranlukast a re influenced by the time of dosing. Based on analysis of urinary 6 be ta-hydroxycortisol excretion, there was no evidence that pranlukast mo dified the metabolic activity of cytochrome P-450 3A isoenzymes.