Pharmacokinetics of sertraline and its N-demethyl metabolite in elderly and young male and female volunteers.
A nonblinded study was conducted to compare the pharmacokinetic properties of the selective serotonin reuptake inhibitor sertraline in 22 young (aged 18 to 45 years) and 22 elderly (> 65 years) volunteers, of whom half were male and half were female. In this study, sertraline was administered at a dosage of 200mg once daily (the maximum recommended daily dosage) for 21 days after upward dosage titration from 50 mg/day over a 9-day period. Thus, this study was designed to measure the effect of age and gender on the pharmacokinetic properties of sertraline at the maximum dosage recommended for clinical use. The terminal elimination half-life (t1/2 beta ) of sertraline was similar in young females, elderly males and elderly females (mean t1/2 beta ranged from 32.1 to 36.7 hours in these groups) but shorter (22.4 hours) in the young males. The mean maximum plasma sertraline concentration (Cmax) and the mean steady-state area under the plasma concentration-time curve from time zero to 24 hours postdose (AUC24) were also similar between the young females, elderly males and elderly females, but were approximately 25% lower in the young males. The time to Cmax was unaffected by age or gender and ranged from 6.4 to 6.9 hours. N-Demethylsertraline is the principal metabolite of sertraline and does not contribute significantly to its serotonergic actions. The mean values for N-demethylsertraline trough plasma concentrations, AUC24 and Cmax were comparable in elderly males and females and young females but lower in young males. The ratios of mean AUC24 and Cmax for N-demethylsertraline to the AUC24 and Cmax for sertraline were similar between the 4 groups.
Ronfeld
R A
RA
Pfizer Central Research, Groton, Connecticut, USA.
Tremaine
L M
LM
Wilner
K D
KD
D015057:1-Naphthylamine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000928:Antidepressive Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D017367:Selective Serotonin Reuptake Inhibitors / Q000378:metabolism / Q000493:pharmacokinetics*; D020280:Sertraline / Q000031:analogs & derivatives; D012737:Sex Factors
D015057:1-Naphthylamine; D000928:Antidepressive Agents; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline; C065162:desmethylsertraline