T. Tateishi et al., PHARMACOKINETICS OF KW-4679 IN THE ELDERLY - SINGLE-DOSE AND MULTIPLE-DOSE TRIALS, Drugs under experimental and clinical research, 24(1), 1998, pp. 1-7
We evaluated the pharmacokinetics of KW-4679, a new antiallergic agent
, in the elderly in trials of both single and multiple dosing. In the
single-dose trial, the pharmacokinetics of a single dose of 10 mg KW-4
679 in elderly male subjects was compared with those in young male sub
jects. in the multiple-dose trial lasting 6 consecutive days with elde
rly male subjects, the pharmacokinetics of the last dose of 10 mg KW-4
679 were compared with those of the first dose to evaluate the accumul
ation of KW-4679 and/or its metabolites. In the single-dose trial, the
maximum concentration and the area under the concentration time curve
of KW-4679 in the elderly subjects were significantly greater than th
ose in the young subjects while the apparent total body clearance was
significantly lower in the elderly subjects. There was no significant
difference in the fraction of KW-4679 excreted in the urine between th
e elderly and the young subjects. The renal clearance of KW-4679 in th
e elderly subjects was significantly lower than that in the young subj
ects. Although the renal clearance was correlated with the creatinine
clearance the renal clearance was significantly greater than the creat
inine clearance, suggesting that this agent undergoes renal tubular se
cretion. In the multiple-dose trial, all pharmacokinetic parameters ex
amined, except the maximum concentration, showed no difference between
the first and the last administration. No accumulation of KW-4679 or
its metabolites could be detected in the elderly subjects examined in
the 6-day multiple-dose trial, though the present results suggest the
dose should be reduced in the elderly subjects who have lower creatini
ne clearance.