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The Population Pharmacokinetics of Citalopram After Deliberate Self-Poisoning: A Bayesian Approach

Friberg, LE, Isbister, GK, Hackett, LP and Duffull, SB (2005). The Population Pharmacokinetics of Citalopram After Deliberate Self-Poisoning: A Bayesian Approach. Journal of Pharmacokinetics and Pharmacodynamics,32(3-4):571-605.

Document type: Journal Article
Citation counts: Scopus Citation Count Cited 37 times in Scopus Article | Citations

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Title The Population Pharmacokinetics of Citalopram After Deliberate Self-Poisoning: A Bayesian Approach
Author Friberg, LE
Isbister, GK
Hackett, LP
Duffull, SB
Journal Name Journal of Pharmacokinetics and Pharmacodynamics
Publication Date 2005
Volume Number 32
Issue Number 3-4
ISSN 1567-567X   (check CDU catalogue open catalogue search in new window)
Scopus ID 2-s2.0-28444470848
Start Page 571
End Page 605
Total Pages 35
Place of Publication US
Publisher Springer New York LLC
Field of Research 1115 - Pharmacology and Pharmaceutical Sciences
HERDC Category C1 - Journal Article (DEST)
Abstract Defining the pharmacokinetics of drugs in overdose is complicated. Deliberate self-poisoning is generally impulsive and associated with poor accuracy in dose history. In addition, early blood samples are rarely collected to characterize the whole plasma-concentration time profile and the effect of decontamination on the pharmacokinetics is uncertain. The aim of this study was to explore a fully Bayesian methodology for population pharmacokinetic analysis of data that arose from deliberate self-poisoning with citalopram. Prior information on the pharmacokinetic parameters was elicited from 14 published studies on citalopram when taken in therapeutic doses. The data set included concentration-time data from 53 patients studied after 63 citalopram overdose events (dose range: 20-1700 mg). Activated charcoal was administered between 0.5 and 4 h after 17 overdose events. The clinical investigator graded the veracity of the patients' dosing history on a 5-point ordinal scale. Inclusion of informative priors stabilised the pharmacokinetic model and the population mean values could be estimated well. There were no indications of non-linear clearance after excessive doses. The final model included an estimated uncertainty of the dose amount which in a simulation study was shown to not affect the model's ability to characterise the effects of activated charcoal. The effect of activated charcoal on clearance and bioavailability was pronounced and resulted in a 72% increase and 22% decrease, respectively. These findings suggest charcoal administration is potentially beneficial after citalopram overdose. The methodology explored seems promising for exploring the dose-exposure relationship in the toxicological settings.
Keywords informative priors
Bayesian analysis
MCMC
drug overdose
activated charcoal
dosing history
citalopram
toxicity
poisoning
DOI http://dx.doi.org/10.1007/s10928-005-0022-6   (check subscription with CDU E-Gateway service for CDU Staff and Students  check subscription with CDU E-Gateway in new window)
 
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