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Journal of Clinical Pharmacy and Therapeutics
Article . 2013 . Peer-reviewed
License: Wiley Online Library User Agreement
Data sources: Crossref
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Estimation of CYP2D6*10 genotypes on citalopram disposition in Chinese subjects by population pharmacokinetic assay

Authors: Chen, B.; Xu, Y.; Jiang, T.; Feng, R.; Sun, J.; Zhang, W.; Yang, W.; +3 Authors

Estimation of CYP2D6*10 genotypes on citalopram disposition in Chinese subjects by population pharmacokinetic assay

Abstract

There is great interindividual variability in citalopram (CIT) pharmacokinetics. We attempted to establish a population pharmacokinetic (PPK) model of CIT in Chinese healthy subjects, to evaluate the effect of genetic polymorphism on CIT pharmacokinetics and to compare the PPK and non-compartmental (NCA) assays in the estimation of CIT bioequivalence.Blood samples of 23 healthy subjects were collected after administration of CIT; plasma concentration of CIT was analysed using LC/MS-MS. CYP2C19 and CYP2D6*10 genotypes were determined. PPK model was established by using nonlinear mixed-effect modelling (NONMEM). The model was evaluated using goodness-of-fit plots and relative error measurements. Bioequivalence of CIT was evaluated by both PPK and NCA method.The estimated population absorption rate constant (ka ), clearance (CL/F) and volume of distribution (Vd/F) in Chinese healthy subjects are 0.64 L/h, 12.7 L/h and 705 L, respectively. Different CYP2C19 and CYP2D6 genotypes have impacts on CIT pharmacokinetics. There is about 5.5% decrement of CL/F for each CYP2C19*2 or CYP2D6*10 allele. The 90% confidence interval of CIT bioavailability obtained from NCA and PPK model were 96.4-105.4% and 92.5-103.4%, respectively.The PPK of CIT is best characterized by a one-compartment disposition model with first-order absorption. CYP2C19 and CYP2D6 genotypes have impacts on the CL/F of CIT. Bioequivalence of CIT can be estimated by both NCA and PPK model.

Country
United States
Related Organizations
Keywords

Adult, Male, Genotype, Chemistry, Pharmaceutical, Population, Citalopram, Young Adult, Asian People, Pharmacy and Pharmacology, Health Sciences, Humans, Non‐Compartment, Bioequivalence, Cross-Over Studies, Models, Statistical, Polymorphism, Genetic, Population Pharmacokinetic, Antidepressive Agents, Cytochrome P-450 CYP2C19, Cytochrome P-450 CYP2D6, Therapeutic Equivalency, CYP 2 C 19, Aryl Hydrocarbon Hydroxylases, CYP 2 D 6

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    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
6
Top 10%
Average
Average
bronze