title: The effect of decontamination procedures on the pharmacokinetics of venlafaxine in overdose.
abstract: The aim of this work was to investigate the pharmacokinetics (PK) of venlafaxine in overdose and the effects of single-dose activated charcoal (SDAC) and whole-bowel irrigation (WBI), alone or in combination, as methods of decontamination. The data included 339 concentration-time points from 76 venlafaxine overdose events (median dose 2,625 (150-13,500 mg)); 69 were slow-release doses. SDAC, WBI, a combination of both, or no decontamination were administered to patients as decided by the treating clinician. The data were modeled using WinBUGS (Windows Bayesian Inference Using Gibbs Sampling). A one-compartment model with first-order input and elimination provided an adequate description of the data. SDAC increased clearance (CL) of venlafaxine by 35%, and SDAC and WBI combined reduced the fraction absorbed by 29%. However, the latter produced a greater reduction in maximum plasma concentration (C(max)) for a similar drop in area under the plasma concentration-time curve (AUC). Both SDAC alone, and a combination of SDAC and WBI, decreased the AUC after venlafaxine overdose, but the combination may be more beneficial because it reduces peak concentrations to a greater extent.
authors.affiliation: School of Pharmacy, University of Otago, Dunedin, New Zealand. pavan.kumar@otago.ac.nz
authors.forename: V V P
authors.initials: VV
authors.lastname: Kumar
authors.forename: S
authors.initials: S
authors.lastname: Oscarsson
authors.forename: L E
authors.initials: LE
authors.lastname: Friberg
authors.forename: G K
authors.initials: GK
authors.lastname: Isbister
authors.forename: L P
authors.initials: LP
authors.lastname: Hackett
authors.forename: S B
authors.initials: SB
authors.lastname: Duffull
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019540:Area Under Curve; D002606:Charcoal / Q000008:administration & dosage / Q000627:therapeutic use*; D003511:Cyclohexanols / Q000493:pharmacokinetics* / Q000506:poisoning*; D003666:Decontamination / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D062787:Drug Overdose / Q000378:metabolism; D005260:Female; D006801:Humans; D041741:Lower Gastrointestinal Tract; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D008954:Models, Biological; D011446:Prospective Studies; D017367:Selective Serotonin Reuptake Inhibitors / Q000493:pharmacokinetics* / Q000506:poisoning*; D007507:Therapeutic Irrigation; D000069470:Venlafaxine Hydrochloride; D055815:Young Adult
chemical_list: D002606:Charcoal; D003511:Cyclohexanols; D017367:Selective Serotonin Reuptake Inhibitors; D000069470:Venlafaxine Hydrochloride