Estimation of CYP2 D6*10 genotypes on citalopram disposition in Chinese subjects by population pharmacokinetic assay.
What is known and objective 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...
| Publicado en: | Journal of Clinical Pharmacy & Therapeutics Vol. 38; no. 6; pp. 504 - 512 |
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| Autores principales: | , , , , , , , , , |
| Formato: | equations & formulas research tables/charts randomized controlled trial Journal Article |
| Publicado: |
Wiley-Blackwell
Dec2013
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=104150457&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 104150457 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 02694727 EV4 jtl: Journal of Clinical Pharmacy & Therapeutics issn: 02694727 maglogo: Y pubinfo: dt: Dec2013 vid: 38 iid: 6 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 104150457 91673870 10.1111/jcpt.12029 104150457 ppf: 504 ppct: 8 formats: fmt: @attributes: type: P tig: atl: Estimation of CYP2 D6*10 genotypes on citalopram disposition in Chinese subjects by population pharmacokinetic assay. aug: au: Chen, B. Xu, Y. Jiang, T. Feng, R. Sun, J. Zhang, W. Yang, W. Li, J. Adeniyi, O. Chen, H. affil: Department of Pharmacy, Ruijin Hospital School of Medicine Shanghai Jiaotong University sug: subj: Oxidoreductases Genotype Biological Assay Citalopram Pharmacokinetics Human Citalopram Blood Biological Availability Models, Statistical Chromatography, Liquid Methods Mass Spectrometry Methods Descriptive Statistics Goodness of Fit Chi Square Test Randomized Controlled Trials Crossover Design China Male Adult Polymerase Chain Reaction Data Analysis Software Post Hoc Analysis Kruskal-Wallis Test Mann-Whitney U Test Analysis of Variance Confidence Intervals Funding Source Adult: 19-44 years Male ab: What is known and objective 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. Methods Blood samples of 23 healthy subjects were collected after administration of CIT; plasma concentration of CIT was analysed using LC/ MS- MS. CYP2 C19 and CYP2 D6*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. Results and discussion 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 CYP2 C19 and CYP2 D6 genotypes have impacts on CIT pharmacokinetics. There is about 5.5% decrement of CL/ F for each CYP2 C19*2 or CYP2 D6*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. What is new and conclusion The PPK of CIT is best characterized by a one-compartment disposition model with first-order absorption. CYP2 C19 and CYP2 D6 genotypes have impacts on the CL/F of CIT. Bioequivalence of CIT can be estimated by both NCA and PPK model. pubtype: Academic Journal doctype: equations & formulas research tables/charts randomized controlled trial Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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