PHARMACOKINETICS OF SERTINDOLE IN HEALTHY-YOUNG AND ELDERLY MALE AND FEMALE SUBJECTS

Objective: The pharmacokinetic disposition of oral sertindole, a new s elective antipsychotic compound, in young and elderly male and female subjects was investigated. Study design: A total of 46 subjects (12 yo ung males, 11 elderly males, II young females, and 12 elderly females) received 4 mg/day sertindole (once a day; days 1 through 3) for 3 con secutive days, 8 mg/day sertindole for 3 consecutive days (days 4 thro ugh 6), and 12 mg/day sertindole for 10 consecutive days (days 7 throu gh 16). Results: Age and gender did not appear to have any effect on t he plasma binding of sertindole, despite a lon er albumin concentratio n in elderly subjects. After multiple dosing of 12 mg sertindole, the mean peak plasma concentration (C-max) values for young and elderly fe male subjects were 20% and 31% higher than those observed for male sub jects of comparable age (p < 0.05). The mean values for area under the plasma concentration-time curve [AUC(0-24)] of female subjects were 2 9% higher than those observed in male subjects of similar age (p < 0.0 5). There were no statistically significant age-related differences in C-max and AUC(0-24) (or apparent total plasma clearance), and there w ere no gender-or age-related differences for the elimination rate cons tant or values for apparent volume of distribution during the terminal elimination phase after the last 12 mg dose on day 16 (p > 0.05). Con clusions: There are no differences between young and elderly subjects in the absorption and elimination of sertindole. The higher C-max and AUC values in females may be a result of a higher extent of absorption or a dependence of sertindole clearance on lean body mass.