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Serum disposition of sertraline, N-desmethylsertraline and paroxetine: A pharmacokinetic evaluation of repeated drug concentration measurements during 6 months of treatment for major depression

Reis, Margareta LU ; Aberg-Wistedt, A; Agren, H; Höglund, Peter LU ; Akerblad, AC and Bengtsson, F (2004) In Human Psychopharmacology: Clinical and Experimental 19(5). p.283-291
Abstract
Sertraline and paroxetine are frequently prescribed SSRIs for long-term treatment of major depression. Nevertheless, continuous follow-ups of drug concentrations prevailing in patients during the whole treatment period are not available. Hence, in a large phase IV clinical trial, a total of 353 patients with major depression were enrolled for a 6-month comparison of sertraline (50-150 mg daily) and paroxetine (20-60 mg daily). The present study reports the pharmacokinetic results of up to eight serum samples per patient. 1. A profound variability was found in the interindividual steady state and trough serum levels of sertraline, desmethylsertraline and paroxetine: the coefficient of variation (CV) was 59% for sertraline, 51% for... (More)
Sertraline and paroxetine are frequently prescribed SSRIs for long-term treatment of major depression. Nevertheless, continuous follow-ups of drug concentrations prevailing in patients during the whole treatment period are not available. Hence, in a large phase IV clinical trial, a total of 353 patients with major depression were enrolled for a 6-month comparison of sertraline (50-150 mg daily) and paroxetine (20-60 mg daily). The present study reports the pharmacokinetic results of up to eight serum samples per patient. 1. A profound variability was found in the interindividual steady state and trough serum levels of sertraline, desmethylsertraline and paroxetine: the coefficient of variation (CV) was 59% for sertraline, 51% for desmethylsertraline, 27% for the ratio desmethylsertraline/sertraline (50 mg/day), and 71% for paroxetine (20 mg/day). The intraindividual CV for the ratio desmethylsertraline/sertraline was only 19%, indicating intraindividual metabolizing stability over time. Both sertraline and paroxetine displayed sex differences in the dose-concentration correlation. 2. It was possible to predict sertraline, but not paroxetine, steady state levels. 3. The terminal elimination t1/2 for both drugs after 6 months of treatments was similar to data previously reported from short-term withdrawal studies. 4. No correlation between serum drug concentrations and clinical effect was detected for either sertraline or paroxetine. For the future, continuous efforts are warranted to perform PK investigations in the natural clinical setting in which the drugs are usually prescribed. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
serum concentrations, sertraline, paroxetine
in
Human Psychopharmacology: Clinical and Experimental
volume
19
issue
5
pages
283 - 291
publisher
John Wiley & Sons
external identifiers
  • wos:000222875100001
  • pmid:15252820
  • scopus:4243109692
ISSN
0885-6222
DOI
10.1002/hup.599
language
English
LU publication?
yes
id
a65d85bb-a016-4447-8175-037ef66bfc42 (old id 272473)
date added to LUP
2007-10-26 15:47:16
date last changed
2017-07-23 03:54:46
@article{a65d85bb-a016-4447-8175-037ef66bfc42,
  abstract     = {Sertraline and paroxetine are frequently prescribed SSRIs for long-term treatment of major depression. Nevertheless, continuous follow-ups of drug concentrations prevailing in patients during the whole treatment period are not available. Hence, in a large phase IV clinical trial, a total of 353 patients with major depression were enrolled for a 6-month comparison of sertraline (50-150 mg daily) and paroxetine (20-60 mg daily). The present study reports the pharmacokinetic results of up to eight serum samples per patient. 1. A profound variability was found in the interindividual steady state and trough serum levels of sertraline, desmethylsertraline and paroxetine: the coefficient of variation (CV) was 59% for sertraline, 51% for desmethylsertraline, 27% for the ratio desmethylsertraline/sertraline (50 mg/day), and 71% for paroxetine (20 mg/day). The intraindividual CV for the ratio desmethylsertraline/sertraline was only 19%, indicating intraindividual metabolizing stability over time. Both sertraline and paroxetine displayed sex differences in the dose-concentration correlation. 2. It was possible to predict sertraline, but not paroxetine, steady state levels. 3. The terminal elimination t1/2 for both drugs after 6 months of treatments was similar to data previously reported from short-term withdrawal studies. 4. No correlation between serum drug concentrations and clinical effect was detected for either sertraline or paroxetine. For the future, continuous efforts are warranted to perform PK investigations in the natural clinical setting in which the drugs are usually prescribed.},
  author       = {Reis, Margareta and Aberg-Wistedt, A and Agren, H and Höglund, Peter and Akerblad, AC and Bengtsson, F},
  issn         = {0885-6222},
  keyword      = {serum concentrations,sertraline,paroxetine},
  language     = {eng},
  number       = {5},
  pages        = {283--291},
  publisher    = {John Wiley & Sons},
  series       = {Human Psychopharmacology: Clinical and Experimental},
  title        = {Serum disposition of sertraline, N-desmethylsertraline and paroxetine: A pharmacokinetic evaluation of repeated drug concentration measurements during 6 months of treatment for major depression},
  url          = {http://dx.doi.org/10.1002/hup.599},
  volume       = {19},
  year         = {2004},
}