The Population Pharmacokinetics of Citalopram After Deliberate Self-Poisoning

A Bayesian Approach

L FRIBERG, Geoffrey Isbister, L HACKETT, S DUFFULL

    Research output: Contribution to journalArticleResearchpeer-review

    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. � 2005 Springer Science+Business Media, Inc.
    Original languageEnglish
    Pages (from-to)571-605
    Number of pages35
    JournalJournal of Pharmacokinetics and Pharmacodynamics
    Volume32
    Issue number3-4
    Publication statusPublished - 2005

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    Citalopram
    Bayes Theorem
    Poisoning
    Charcoal
    Pharmacokinetics
    Population
    History
    Drug Overdose
    Decontamination
    Toxicology
    Biological Availability
    Uncertainty
    Research Personnel

    Cite this

    FRIBERG, L ; Isbister, Geoffrey ; HACKETT, L ; DUFFULL, S. / The Population Pharmacokinetics of Citalopram After Deliberate Self-Poisoning : A Bayesian Approach. In: Journal of Pharmacokinetics and Pharmacodynamics. 2005 ; Vol. 32, No. 3-4. pp. 571-605.
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    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. � 2005 Springer Science+Business Media, Inc.",
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    The Population Pharmacokinetics of Citalopram After Deliberate Self-Poisoning : A Bayesian Approach. / FRIBERG, L; Isbister, Geoffrey; HACKETT, L; DUFFULL, S.

    In: Journal of Pharmacokinetics and Pharmacodynamics, Vol. 32, No. 3-4, 2005, p. 571-605.

    Research output: Contribution to journalArticleResearchpeer-review

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    T1 - The Population Pharmacokinetics of Citalopram After Deliberate Self-Poisoning

    T2 - A Bayesian Approach

    AU - FRIBERG, L

    AU - Isbister, Geoffrey

    AU - HACKETT, L

    AU - DUFFULL, S

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    N2 - 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. � 2005 Springer Science+Business Media, Inc.

    AB - 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. � 2005 Springer Science+Business Media, Inc.

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