- Title
- Population pharmacokinetics and pharmacodynamics of escitalopram in overdose and the effect of activated charcoal
- Creator
- van Gorp, Freek; Duffull, Stephen; Hackett, L. Peter; Isbister, Geoffrey K.
- Relation
- British Journal of Clinical Pharmacology Vol. 73, Issue 3, p. 402-410
- Publisher Link
- http://dx.doi.org/10.1111/j.1365-2125.2011.04091.x
- Publisher
- Wiley-Blackwell Publishing
- Resource Type
- journal article
- Date
- 2012
- Description
- Aims: To describe the pharmacokinetics and pharmacodynamics (PKPD) of escitalopram in overdose and its effect on QT prolongation, including the effectiveness of single dose activated charcoal (SDAC). Methods: The data set included 78 escitalopram overdose events (median dose, 140 mg [10–560 mg]). SDAC was administered 1.0 to 2.6 h after 12 overdoses (15%). A fully Bayesian analysis was undertaken in WinBUGS 1.4.3, first for a population pharmacokinetic (PK) analysis followed by a PKPD analysis. The developed PKPD model was used to predict the probability of having an abnormal QT as a surrogate for torsade de pointes. Results: A one compartment model with first order input and first-order elimination described the PK data, including uncertainty in dose and a baseline concentration for patients taking escitalopram therapeutically. SDAC reduced the fraction absorbed by 31% and reduced the individual predicted area under the curve adjusted for dose (AUCi/dose). The absolute QT interval was related to the observed heart rate with an estimated individual heart rate correction factor (a = 0.35). The heart rate corrected QT interval (QTc) was linearly dependent on predicted escitalopram concentration [slope = 87 ms/(mg l–1)], using a hypothetical effectcompartment (half-life of effect-delay, 1.0h). Administration of SDAC significantly reduced QT prolongation and was shown to reduce the risk of having an abnormal QT by approximately 35% for escitalopram doses above 200 mg. Conclusions: There was a dose-related lengthening of the QT interval that lagged the increase in drug concentration. SDAC resulted in a moderate reduction in fraction of escitalopram absorbed and reduced the risk of the QT interval being abnormal.
- Subject
- escitalopram; overdose; pharmacodynamics; pharmacokinetics; QT interval
- Identifier
- http://hdl.handle.net/1959.13/1046007
- Identifier
- uon:14561
- Identifier
- ISSN:0306-5251
- Rights
- The definitive version is available at www.onlinelibrary.wiley.com
- Language
- eng
- Full Text
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