title: Exposure-outcome analysis in depressed patients treated with paroxetine using population pharmacokinetics.
abstract: OBJECTIVE
  This study investigated population pharmacokinetics of paroxetine, and then performed an integrated analysis of exposure and clinical outcome using population pharmacokinetic parameter estimates in depressed patients treated with paroxetine.
  
  
  METHODS
  A total of 271 therapeutic drug monitoring (TDM) data were retrospectively collected from 127 psychiatric outpatients. A population nonlinear mixed-effects modeling approach was used to describe serum concentrations of paroxetine. For 83 patients with major depressive disorder, the treatment response rate and the incidence of adverse drug reaction (ADR) were characterized by logistic regression using daily dose or area under the concentration-time curve (AUC) estimated from the final model as a potential exposure predictor.
  
  
  RESULTS
  One compartment model was developed. The apparent clearance of paroxetine was affected by age as well as daily dose administered at steady-state. Overall treatment response rate was 72%, and the incidence of ADR was 30%. The logistic regression showed that exposure predictors were not associated with treatment response or ADR in the range of dose commonly used in routine practice. However, the incidence of ADR increased with the increase of daily dose or AUC for the patients with multiple concentrations.
  
  
  CONCLUSIONS
  In depressed patients treated with paroxetine, TDM may be of limited value for individualization of treatment.
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Samsung Medical Center, Seoul, Republic of Korea.
authors.forename: Jung-Ryul
authors.initials: JR
authors.lastname: Kim
authors.affiliation: Department of Laboratory Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Republic of Korea.
authors.forename: Hye In
authors.initials: HI
authors.lastname: Woo
authors.affiliation: Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Mi-Ryung
authors.initials: MR
authors.lastname: Chun
authors.affiliation: Samsung Advanced Institute for Health Sciences and Technology (SAIHST), Sungkyunkwan University, Seoul, Republic of Korea.
authors.forename: Shinn-Won
authors.initials: SW
authors.lastname: Lim
authors.affiliation: Clinical Research Division, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Osong, Chungcheongbuk-do, Republic of Korea.
authors.forename: Hae Deun
authors.initials: HD
authors.lastname: Kim
authors.affiliation: Clinical Research Division, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Osong, Chungcheongbuk-do, Republic of Korea.
authors.forename: Han Sung
authors.initials: HS
authors.lastname: Na
authors.affiliation: Clinical Research Division, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Osong, Chungcheongbuk-do, Republic of Korea.
authors.forename: Myeon Woo
authors.initials: MW
authors.lastname: Chung
authors.affiliation: Department of Psychiatry, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Woojae
authors.initials: W
authors.lastname: Myung
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Samsung Medical Center, Seoul, Republic of Korea ; Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Soo-Youn
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Department of Psychiatry, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Doh Kwan
authors.initials: DK
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018687:Antidepressive Agents, Second-Generation / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D003865:Major Depressive Disorder / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D008954:Models, Biological; D017711:Nonlinear Dynamics; D017374:Paroxetine / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D012189:Retrospective Studies; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018687:Antidepressive Agents, Second-Generation; D017374:Paroxetine; D017367:Selective Serotonin Reuptake Inhibitors
keywords: NONMEM; exposure–outcome relationship; paroxetine; population pharmacokinetics; therapeutic drug monitoring