Steady-state pharmacokinetics of citalopram in young and elderly subjects.
OBJECTIVE
To compare the steady-state pharmacokinetics of citalopram after multiple-dose administration in elderly and young subjects, and to correlate pharmacokinetic measurements with tolerability.


METHODS
Single-blind, multiple-dose, dose-escalating, randomized, placebo-controlled trial.


METHODS
The Orlando Clinical Research Center, Orlando, Florida.


METHODS
Twenty-four healthy elderly and eight healthy young men and women.


METHODS
Subjects randomized to citalopram received 10 mg once/day for the first week, 20 mg once/day for the second week, and 40 mg once/day for the remaining 3 weeks.


RESULTS
Blood samples were collected weekly to determine steady-state pharmacokinetics of citalopram and its primary metabolites. During dose escalation, samples were collected just before dose increase. After the final dose, blood samples were collected periodically over 480 hours to characterize the terminal elimination phase. In elderly subjects, maximum concentration, time associated with the maximum concentration, area under the concentration versus time curve from 0-24 hours, half-life, and volume of distribution were all slightly increased; oral clearance was slightly decreased. However, only half-life was statistically different between the groups, 30% longer in the elderly. In addition, the frequency and severity of adverse events were comparable between the two age groups and did not appear to be dose related.


CONCLUSIONS
The pharmacokinetics and tolerability of citalopram in elderly subjects are similar to those observed in younger subjects. The slight differences observed in the elderly likely reflect declining liver and kidney function.
Gutierrez
M
M
Department of Pharmacokinetics, Forest Laboratories, Inc., New York, New York 10022, USA.
Abramowitz
W
W
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000375:Aging / Q000097:blood / Q000378:metabolism*; D018687:Antidepressive Agents, Second-Generation / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D015283:Citalopram / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D010919:Placebos; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D016037:Single-Blind Method
D018687:Antidepressive Agents, Second-Generation; D015283:Citalopram; D010919:Placebos; D017367:Selective Serotonin Reuptake Inhibitors