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Title:
Application of pharmacokinetic-pharmacodynamic modelling in management of QT abnormalities after citalopram overdose | Intensive Care Medicine
Description:
Objective To develop guidelines for the management of QT prolongation after citalopram overdose, including decontamination with single-dose activated charcoal (SDAC) and cardiac monitoring. Design Simulation study using a previously developed pharmacokinetic-pharmacodynamic (PKPD) model which predicted the time-course of QT prolongation and the effect of citalopram dose and use of SDAC on QT prolongation. Main measures and results The previously developed PKPD model was used to address the following in patients following citalopram overdose: (1) Above what dose should patients be decontaminated? (2) Above what dose should patients have cardiac monitoring? (3) For what period of time should patients be monitored? The primary outcome was QT,RR combinations above an abnormal threshold as a surrogate predictor of torsades de pointes. Simulations were performed using MATLAB for an overdose patient with typical demographics: 30-year-old female with a heart rate of 79 bpm taking citalopram therapeutically. The simulations showed: (1) There was significant benefit associated with the administration of SDAC to patients following citalopram overdose ingesting > 600 mg; (2) With citalopram overdoses > 1,000 mg it was advisable to give SDAC and cardiac monitor the patient; (3) The risk of developing future abnormal QT,RR combinations was less than 1% in patients with normal QT,RR combinations up to 13 h post-dose, so the minimum monitoring time for citalopram overdoses > 1,000 mg should be 13 h. Recommended dose levels for intervention should be lowered in older patients and patients with tachycardia, while men are less sensitive to QT prolongation. Conclusions Guidelines for the management of QT prolongation after citalopram overdose were developed. We believe the model will help clinicians to decide which patients to decontaminate and monitor.
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article, citalopram, google, scholar, pubmed, cas, overdose, isbister, patients, prolongation, toxicol, clinical, pharmacokineticpharmacodynamic, management, friberg, interval, clin, privacy, cookies, content, data, research, modelling, duffull, dose, qtrr, drug, information, publish, search, geoffrey, sdac, cardiac, study, model, pointes, heart, access, subjects, med, pharmacol, log, journal, intensive, care, lena, guidelines, activated, charcoal, monitoring,
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month download article/chapter undertook pharmacokinetic-pharmacodynamic modelling previously developed pharmacokinetic-pharmacodynamic pharmacokinetic-pharmacodynamic modelling qt-rr interval relationship steady-state pharmacokinetics full article pdf clinical toxicology le couteur dg privacy choices/manage cookies related gene inhibition oral drug overdose multiple drug interactions randomized clinical trial single-dose activated charcoal article isbister related subjects qt interval prolongation european economic area torsades de pointes hospital pharmacist interventions chronic kidney disease relative toxicity acute coronary syndromes breast fed infants torsade de pointes balit cr high intrasubject stability alice wallenberg foundation newcastle mater hospital qt-rr relationship healthy subjects conditions privacy policy national data elements acta pharmacol toxicol recommended dose levels cardiac arrest [abstract] isbister gk accepting optional cookies heart rate correction citalopram overdose—review clinical study article log check access instant access journal finder publish develop guidelines conclusions guidelines population pharmacokinetics article cite
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- The previously developed PKPD model was used to address the following in patients following citalopram overdose: (1) Above what dose should patients be decontaminated?
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headline:Application of pharmacokinetic-pharmacodynamic modelling in management of QT abnormalities after citalopram overdose
description:To develop guidelines for the management of QT prolongation after citalopram overdose, including decontamination with single-dose activated charcoal (SDAC) and cardiac monitoring. Simulation study using a previously developed pharmacokinetic-pharmacodynamic (PKPD) model which predicted the time-course of QT prolongation and the effect of citalopram dose and use of SDAC on QT prolongation. The previously developed PKPD model was used to address the following in patients following citalopram overdose: (1) Above what dose should patients be decontaminated? (2) Above what dose should patients have cardiac monitoring? (3) For what period of time should patients be monitored? The primary outcome was QT,RR combinations above an abnormal threshold as a surrogate predictor of torsades de pointes. Simulations were performed using MATLAB for an overdose patient with typical demographics: 30-year-old female with a heart rate of 79 bpm taking citalopram therapeutically. The simulations showed: (1) There was significant benefit associated with the administration of SDAC to patients following citalopram overdose ingesting > 600 mg; (2) With citalopram overdoses > 1,000 mg it was advisable to give SDAC and cardiac monitor the patient; (3) The risk of developing future abnormal QT,RR combinations was less than 1% in patients with normal QT,RR combinations up to 13 h post-dose, so the minimum monitoring time for citalopram overdoses > 1,000 mg should be 13 h. Recommended dose levels for intervention should be lowered in older patients and patients with tachycardia, while men are less sensitive to QT prolongation. Guidelines for the management of QT prolongation after
citalopram overdose were developed. We believe the model will
help clinicians to decide which patients to decontaminate and
monitor.
datePublished:2006-05-10T00:00:00Z
dateModified:2006-05-10T00:00:00Z
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Citalopram
Clinical guidelines
Overdose
Pharmacokinetic-pharmacodynamic modelling
Simulation
Toxicity
Intensive / Critical Care Medicine
Anesthesiology
Emergency Medicine
Pneumology/Respiratory System
Pain Medicine
Pediatrics
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headline:Application of pharmacokinetic-pharmacodynamic modelling in management of QT abnormalities after citalopram overdose
description:To develop guidelines for the management of QT prolongation after citalopram overdose, including decontamination with single-dose activated charcoal (SDAC) and cardiac monitoring. Simulation study using a previously developed pharmacokinetic-pharmacodynamic (PKPD) model which predicted the time-course of QT prolongation and the effect of citalopram dose and use of SDAC on QT prolongation. The previously developed PKPD model was used to address the following in patients following citalopram overdose: (1) Above what dose should patients be decontaminated? (2) Above what dose should patients have cardiac monitoring? (3) For what period of time should patients be monitored? The primary outcome was QT,RR combinations above an abnormal threshold as a surrogate predictor of torsades de pointes. Simulations were performed using MATLAB for an overdose patient with typical demographics: 30-year-old female with a heart rate of 79 bpm taking citalopram therapeutically. The simulations showed: (1) There was significant benefit associated with the administration of SDAC to patients following citalopram overdose ingesting > 600 mg; (2) With citalopram overdoses > 1,000 mg it was advisable to give SDAC and cardiac monitor the patient; (3) The risk of developing future abnormal QT,RR combinations was less than 1% in patients with normal QT,RR combinations up to 13 h post-dose, so the minimum monitoring time for citalopram overdoses > 1,000 mg should be 13 h. Recommended dose levels for intervention should be lowered in older patients and patients with tachycardia, while men are less sensitive to QT prolongation. Guidelines for the management of QT prolongation after
citalopram overdose were developed. We believe the model will
help clinicians to decide which patients to decontaminate and
monitor.
datePublished:2006-05-10T00:00:00Z
dateModified:2006-05-10T00:00:00Z
pageStart:1060
pageEnd:1065
sameAs:https://doi.org/10.1007/s00134-006-0183-9
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Citalopram
Clinical guidelines
Overdose
Pharmacokinetic-pharmacodynamic modelling
Simulation
Toxicity
Intensive / Critical Care Medicine
Anesthesiology
Emergency Medicine
Pneumology/Respiratory System
Pain Medicine
Pediatrics
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