title: The pharmacokinetics of sertraline in overdose and the effect of activated charcoal.
abstract: OBJECTIVE
  To investigate the pharmacokinetics (PK) of sertraline in overdose and the effect of single dose activated charcoal (SDAC).
  
  
  METHODS
  Patients presenting to a toxicology unit with sertraline overdoses had demographic and clinical information recorded, and serial serum collected for measurement of sertraline concentrations. Monolix® version 4.2 was used to develop a population PK model of sertraline overdose and the effect of SDAC. Uncertainty in dose time was accounted for by shifting dose time using lag time with between subject variability (BSV). BSV on relative fraction absorbed was used to model uncertainty in dose.
  
  
  RESULTS
  There were 77 timed sertraline concentrations measured in 28 patients with sertraline overdoses with a median dose of 1550 mg (250-5000 mg). SDAC was given to seven patients between 1.5 and 4 h post-overdose. A one compartment model with lag time of 1 h and first order input and elimination adequately described the data. Including BSV on both lag time and relative fraction absorbed improved the model. The population PK parameter estimates for absorption rate constant, volume of distribution and clearance were 0.895 h(-1) , 5340 l and 130 l h(-1) , respectively. The calculated half-life of sertraline following overdose was 28 h (IQR 19.4-30.6h). When given up to 4 h post-overdose, SDAC significantly increased the clearance of sertraline by a factor of 1.9, decreased the area under the curve and decreased the maximum plasma concentration (Cmax ).
  
  
  CONCLUSIONS
  Sertraline had linear kinetics in overdose with parameter values similar to those in therapeutic use. SDAC is effective in increasing clearance when given 1.5 to 4 h post-overdose.
authors.affiliation: Faculty of Health & Medicine, University of Newcastle, Newcastle, New South Wales, Australia.
authors.forename: Joyce M
authors.initials: JM
authors.lastname: Cooper
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Duffull
authors.forename: Ana S
authors.initials: AS
authors.lastname: Saiao
authors.forename: Geoffrey K
authors.initials: GK
authors.lastname: Isbister
mesh_terms: D000293:Adolescent; D000328:Adult; D000931:Antidotes / Q000008:administration & dosage*; D019540:Area Under Curve; D002606:Charcoal / Q000008:administration & dosage*; D062787:Drug Overdose; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D011446:Prospective Studies; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics; D020280:Sertraline / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013997:Time Factors; D035501:Uncertainty; D055815:Young Adult
chemical_list: D000931:Antidotes; D002606:Charcoal; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline
keywords: activated charcoal; overdose; pharmacokinetics; poisoning; sertraline