NDLI: A population pharmacokinetic model for R- and S-citalopram and desmethylcitalopram in Alzheimer’s disease patients with agitation

Content Provider	Springer Nature Link
Author	Akil, Ayman Bies, Robert R. Pollock, Bruce G. Avramopoulos, Dimitrios Devanand, D. P. Mintzer, Jacobo E. Porsteinsson, Anton P. Schneider, Lon S. Weintraub, Daniel Yesavage, Jerome Shade, David M. Lyketsos, Constantine G.
Copyright Year	2015
Abstract	The citalopram for Alzheimer’s disease trial evaluated citalopram for the management for agitation in Alzheimer’s disease patients. Sparse data was available from this elderly patient population. A nonlinear mixed effects population pharmacokinetic modeling approach was used to describe the pharmacokinetics of R- and S-citalopram and their primary metabolite (desmethylcitalopram). A structural model with 4 compartments (one compartment/compound) with linear oral absorption and elimination described the data adequately. Overall, the model showed that clearance of the R-enantiomer was slower than the clearance of the S-enantiomer. Without accounting for any patient-specific covariates, the population estimate of the metabolic clearance of citalopram was 8.6 (R-citalopram) and 14 L/h (S-citalopram). The population estimate of the clearance of desmethylcitalopram was 23.8 (R-Dcit) and 38.5 L/h (S-Dcit). Several patient-specific covariates were found to have a significant effect on the pharmacokinetics of R,S-citalopram and desmethylcitalopram. A significant difference in the metabolic clearance of R-citalopram between males and females (13 vs 9.05 L/h) was identified in this analysis. Both R- and S-citalopram metabolic clearance decreased with age. Additionally, consistent with literature reports S-citalopram metabolic clearance increased with increasing body weight and was significantly influenced by CYPC19 genotype, with a difference of 5.8 L/h between extensive/rapid and intermediate/poor metabolizers. R,S-desmethylcitalopram clearance increased with increasing body weight. This model may allow for the opportunity to delineate the effect of R- and S-citalopram on pharmacodynamics outcomes related to the management of agitation in Alzheimer’s disease.
Starting Page	99
Ending Page	109
Page Count	11
File Format	PDF
ISSN	1567567X
Journal	Journal of Pharmacokinetics and Pharmacodynamics
Volume Number	43
Issue Number	1
e-ISSN	15738744
Language	English
Publisher	Springer US
Publisher Date	2015-11-26
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Citalopram Pharmacokinetics Agitation Alzheimer’s disease Pharmacology/Toxicology Pharmacy Veterinary Medicine Biomedical Engineering Biochemistry
Content Type	Text
Resource Type	Article
Subject	Pharmacology

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