Pharmacokinetics of quetiapine in overdose and the effect of activated charcoal.
The aim of the study was to investigate the pharmacokinetics of quetiapine overdose and the effect of charcoal. The data set included 204 concentration-time points from 54 quetiapine overdose events (median dose 2,700 mg (300-24,000 mg)). Charcoal was administered 0.5-6 h after 19 overdoses. A fully Bayesian methodology for population pharmacokinetic analysis was used and data were modelled using WinBUGS. Uncertainty in the dose history was considered in model building by estimating dose amount and dose time within a possible range. Inclusion of informative priors stabilized the model and population parameter values could be estimated well. A one-compartment model with first-order input and first-order elimination described the data. The final model included uncertainty in dose time. The median and interquartile range of the half-life for individual patients was 6.6 h (4.9-8.4 h). Charcoal was estimated to reduce fraction absorbed by 35%. Co-ingested CYP3A4 inhibitors appeared to decrease clearance and CYP3A4 inducers increase clearance. Charcoal administration may be beneficial after quetiapine overdose.
Isbister
G K
GK
Department of Clinical Toxicology and Pharmacology, Newcastle Mater Hospital, Newcastle and Tropical Toxinology Unit, Menzies School of Health Research, Charles Darwin University, Darwin, Northern Territory, Australia. gsbite@ferntree.com
Friberg
L E
LE
Hackett
L P
LP
Duffull
S B
SB
D000293:Adolescent; D000328:Adult; D000931:Antidotes / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000493:pharmacokinetics* / Q000506:poisoning; D001499:Bayes Theorem; D002606:Charcoal / Q000627:therapeutic use*; D051544:Cytochrome P-450 CYP3A; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D003987:Dibenzothiazepines / Q000493:pharmacokinetics* / Q000506:poisoning; D004305:Dose-Response Relationship, Drug; D062787:Drug Overdose / Q000188:drug therapy; D020536:Enzyme Activators / Q000494:pharmacology; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D008954:Models, Biological; D000069348:Quetiapine Fumarate; D035501:Uncertainty
D000931:Antidotes; D014150:Antipsychotic Agents; D065607:Cytochrome P-450 Enzyme Inhibitors; D003987:Dibenzothiazepines; D020536:Enzyme Activators; D002606:Charcoal; D000069348:Quetiapine Fumarate; D003577:Cytochrome P-450 Enzyme System; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human