1996 Volume 27 Issue 4 Pages 673-681
We evaluated the pharmacokinetics of KW-4679, a new antiallergic agent, in the elderly in single dosing and repeated dosing trials. In, the single dosing trial, the pharmacokinetics of a single dose of 10 mg KW-4679 in elderly male subjects [74±2yrs (mean±SD), n=6] were compared with these in young male subjects (21±1yrs, n=6). In the repeated dosing trial for 6 consecutive days, the pharmacokinetics of the last administration of 10 mg KW-4679 were compared with those of the first administration in elderly male subjects (74±3 yrs, n=6) to determine the accumulation of KW-4679 and/or its metabolites. In the single dosing trial, Cmaxand AUCin the elderly subjects were significantly larger than in the young subjects, while Cl/F was significantly smaller in the elderly subjects. There was no significant difference in the fraction of KW-4679 excreted in the urine between the elderly and the young subjects (69.3 ± 6.3% and 62.5±5.4% in the young and the elderly subjects, respectively). ClR in the elderly subjects (7.52 ± 2.18 L/hr) was significantly smaller than that in the young subjects (14.4± 2.20 L/hr). Although ClR was, correlated with Ccr, ClR was significantly larger than Ccr, implying that this agent undergoes renal tubular secretion. In the repeated dosing trial, all pharmacokinetic parameters examined, except for Cmax, showed no difference between the first and the last administration.
The accumulation of KW-4679 and/or its metabolites could not be detected in the elderly subjects examined in the repeated dosing trial for 6 days, though these results suggested that the dose should be reduced in the elderly subjects who have lower Ccr.
