PHARMACOKINETICS OF THE ACTIVE METABOLITE OF THE PRODRUG REPIRINAST IN HEALTHY CAUCASIAN VOLUNTEERS AFTER A SINGLE ORAL DOSE

The pharmacokinetics of BAY w 8199, the active metabolite of the prodrug repirinast (BAY u 2372), has been investigated after oral administration of 150,300 and 450 mg repirinast to twelve healthy male Caucasians. Plasma BAY w 8199 concentrations were very variable between subjects. The mean peak level (geom. mean; 1s-range) was 0.14 (0.08-0.25), 0.19 (0.13-0.29) and 0.24 (0.14-0.42) mg/l after the 150, 300 and 450 mg doses, respectively. Peak levels were reached 0.5-2.5 h after drug intake. Terminal half-lives were calculated as 5.9 h (150 mg), 8.0 h (300 mg) and 9.8 h (450 mg). The dose proportionality of the plasma profiles of BAY w 8199 and of its excretion in urine was demonstrated by testing several parameters. About 7.4% of each dose (calculated as BAY w 8199) was excreted in urine over 36 h. The renal clearance of about 27 l/h suggests that BAY w 8199 is excreted by tubular secretion in addition to glomerular filtration.