The effect of decontamination procedures on the pharmacokinetics of venlafaxine in overdose.
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.
Kumar
V V P
VV
School of Pharmacy, University of Otago, Dunedin, New Zealand. pavan.kumar@otago.ac.nz
Oscarsson
S
S
Friberg
L E
LE
Isbister
G K
GK
Hackett
L P
LP
Duffull
S B
SB
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
D002606:Charcoal; D003511:Cyclohexanols; D017367:Selective Serotonin Reuptake Inhibitors; D000069470:Venlafaxine Hydrochloride