To investigate the effects of aging on the pharmacokinetics of MCI-186, a novel agent for cerebrovascular disease, we performed a comparative study in parallel groups of young and elderly subjects. The subjects were 14 healthy male volunteers, 7 forming the elderly group (age 65-71 years) and 7 in the young group (age 25-34 years). Five subjects of each group received 100 ml of saline containing 0.5 mg/kg of MCI-186 intravenously via a 30-minute drip infusion, while the remaining 2 subjects in each group received only 100 ml of saline as placebo. The preparations were given twice a day (8: 00 and 20: 00) for two days; 4 times in total. Plasma and urinary concentrations of MCI-186 and its metabolites (glucuronide conjugate, MG and sulfate conjugate, MS) were determined. MCI-186 was well tolerated in all except for one elderly subject who complained of chest discomfort during the first administration. This problem was resolved quickly without treatment during the infusion and was not reproducible. Plasma concentrations of MCI-186 were almost identical in each group and statistical differences were not found among the calculated pharmacokinetic parameters such as maximum concentration (Cmax), minimum concentration (Cmin), area under the curve (AUC) or elimination half life (t1/2). Although there was no statistically significant difference, Cmax in the elderly group was slightly higher than in the young group (1040.7±105.8 ng/ml vs 887.6±171.3 ng/ml, elderly vs young, mean±SD, p=0.127), which could reflect a decrease in the volume of distribution in the elderly group.Ratios of the plasma concentration of the parent drug and the metabolites were almost the same in both groups. Thus, a modification of the dose of MCI-186 for elderly subjects is not required, although a minimum increase of Cmax was found.
