Pharmacokinetics of sertindole in healthy young and elderly male and female subjects.
OBJECTIVE
The pharmacokinetic disposition of oral sertindole, a new selective antipsychotic compound, in young and elderly male and female subjects was investigated.


METHODS
A total of 46 subjects (12 young males, 11 elderly males, 11 young females, and 12 elderly females) received 4 mg/day sertindole (once a day; days 1 through 3) for 3 consecutive days, 8 mg/day sertindole for 3 consecutive days (days 4 through 6), and 12 mg/day sertindole for 10 consecutive days (days 7 through 16).


RESULTS
Age and gender did not appear to have any effect on the plasma binding of sertindole, despite a lower albumin concentration in elderly subjects. After multiple dosing of 12 mg sertindole, the mean peak plasma concentration (Cmax) values for young and elderly female subjects were 20% and 31% higher than those observed for male subjects of comparable age (p < 0.05). The mean values for area under the plasma concentration-time curve [AUC(0-24)] of female subjects were 29% higher than those observed in male subjects of similar age (p < 0.05). There were no statistically significant age-related differences in Cmax and AUC(0-24) (or apparent total plasma clearance), and there were no gender- or age-related differences for the elimination rate constant or values for apparent volume of distribution during the terminal elimination phase after the last 12 mg dose on day 16 (p > 0.05).


CONCLUSIONS
There are no differences between young and elderly subjects in the absorption and elimination of sertindole. The higher Cmax 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.
Wong
S L
SL
Department of Pharmacokinetics, Abbott Laboratories, Abbott Park, IL 60064-3500, USA. shekman.wong@abbott.com
Cao
G
G
Mack
R J
RJ
Granneman
G R
GR
D000042:Absorption; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism*; D014150:Antipsychotic Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000493:pharmacokinetics*; D007211:Indoles / Q000493:pharmacokinetics*; D008297:Male; D012727:Sex Characteristics
D014150:Antipsychotic Agents; D007093:Imidazoles; D007211:Indoles; C066304:sertindole