title: Pharmacokinetics of KW-4679 in the elderly: single-dose and multiple-dose trials.
abstract: 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-4679 in elderly male subjects was compared with those in young male subjects. In the multiple-dose trial lasting 6 consecutive days with elderly male subjects, the pharmacokinetics of the last dose of 10 mg KW-4679 were compared with those of the first dose to evaluate the accumulation 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 those 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 the elderly and the young subjects. The renal clearance of KW-4679 in the elderly subjects was significantly lower than that in the young subjects. Although the renal clearance was correlated with the creatinine clearance, the renal clearance was significantly greater than the creatinine clearance, suggesting that this agent undergoes renal tubular secretion. In the multiple-dose trial, all pharmacokinetic parameters examined, 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 creatinine clearance.
authors.affiliation: Department of Pharmacology, St. Marianna University School of Medicine, Kanagawa, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Tateishi
authors.forename: S
authors.initials: S
authors.lastname: Kobayashi
authors.forename: C
authors.initials: C
authors.lastname: Shigeyama
authors.forename: T
authors.initials: T
authors.lastname: Nakamura
authors.forename: H
authors.initials: H
authors.lastname: Kobayashi
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism*; D018926:Anti-Allergic Agents / Q000493:pharmacokinetics*; D003990:Dibenzoxepins / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D015394:Molecular Structure; D000069605:Olopatadine Hydrochloride; D012016:Reference Values
chemical_list: D018926:Anti-Allergic Agents; D003990:Dibenzoxepins; D000069605:Olopatadine Hydrochloride