title: The effect of decontamination procedures on the pharmacodynamics of venlafaxine in overdose.
abstract: OBJECTIVE
  To investigate the relationship between decontamination procedures and seizure events caused by venlafaxine overdose and to estimate the time at which 90% of patients would have had their first seizure in the presence and absence of decontamination.
  
  
  METHODS
  Data were collected from 319 patients who took an overdose of venlafaxine on 436 occasions. Seizures occurred on 24 of 436 occasions (5%). Patients received one of single dose activated charcoal (SDAC), whole bowel irrigation (WBI), a combination of either (SDAC/WBI) or no decontamination. Logistic regression and time to event analysis were used to investigate the influence of dose and decontamination on the probability of seizures and time to 90% (t(90) ) of seizure, respectively.
  
  
  RESULTS
  A linear logistic regression model described the data. Simulation from the model showed that the probability of seizure was 0.05 (0.03-0.08), 0.19 (0.09-0.35) and 0.75 (0.30-0.96) at 1000, 5000 and 10 000 mg, respectively (median and 95% credible interval). At the mean dose of 2100 mg the odds ratios (OR) in the presence of SDAC, WBI and SDAC/WBI were 0.48 (0.25-0.89), 0.71 (0.35-1.22) and 0.25 (0.08-0.62), respectively. A modified Gompertz model described the time to seizure events. Simulations from the Gompertz model showed that the t(90) values for first seizure was 26 h and was not affected by dose or decontamination procedure.
  
  
  CONCLUSIONS
  SDAC/WBI provided greater benefits than the sum of the independent effects of SDAC and WBI. Patients should be observed for at least 24 h for seizures based on the dose and risk of seizure occurring.
authors.affiliation: School of Pharmacy, University of Otago, Dunedin, New Zealand. pavan.kumar@otago.ac.nz
authors.forename: Venkata V Pavan
authors.initials: VV
authors.lastname: Kumar
authors.forename: Geoffrey K
authors.initials: GK
authors.lastname: Isbister
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Duffull
mesh_terms: D000328:Adult; D000931:Antidotes / Q000008:administration & dosage*; D001499:Bayes Theorem; D001682:Biological Availability; D002606:Charcoal / Q000008:administration & dosage*; D015331:Cohort Studies; D003511:Cyclohexanols / Q000493:pharmacokinetics* / Q000506:poisoning; D003666:Decontamination / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D062787:Drug Overdose; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008657:Metabolic Clearance Rate; D012640:Seizures / Q000139:chemically induced*; D017367:Selective Serotonin Reuptake Inhibitors / Q000493:pharmacokinetics* / Q000506:poisoning; D007507:Therapeutic Irrigation / Q000379:methods*; D013997:Time Factors; D000069470:Venlafaxine Hydrochloride
chemical_list: D000931:Antidotes; D002606:Charcoal; D003511:Cyclohexanols; D017367:Selective Serotonin Reuptake Inhibitors; D000069470:Venlafaxine Hydrochloride