Cytochrome P450 2D6 genotype affects the pharmacokinetics of controlled-release paroxetine in healthy Chinese subjects: comparison of traditional phenotype and activity score systems.
Purpose: This study evaluated the effects of cytochrome P450 (CYP) 2D6 polymorphisms on the pharmacokinetics of controlled-release paroxetine in healthy Chinese subjects and used paroxetine as a tool drug to compare the performance of traditional phenotype and activity score systems. Methods: Pharma...
| Publicado en: | European Journal of Clinical Pharmacology Vol. 71; no. 7; pp. 835 - 842 |
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| Autores principales: | , , , , |
| Formato: | research tables/charts Journal Article |
| Publicado: |
Springer Nature
Jul2015
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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=109798338&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 109798338 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00316970 NP9 jtl: European Journal of Clinical Pharmacology issn: 00316970 maglogo: N pubinfo: dt: Jul2015 vid: 71 iid: 7 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 109798338 103187914 10.1007/s00228-015-1855-6 NLM25967538 109798338 ppf: 835 ppct: 7 formats: fmt: @attributes: type: P tig: atl: Cytochrome P450 2D6 genotype affects the pharmacokinetics of controlled-release paroxetine in healthy Chinese subjects: comparison of traditional phenotype and activity score systems. aug: au: Chen, Rui Wang, Haotian Shi, Jun Shen, Kai Hu, Pei affil: Clinical Pharmacology Research Center, Peking Union Medical College Hospital, 41 Damucang Alley, Xicheng District Beijing 100032 China sug: subj: Genotype Paroxetine Pharmacokinetics Polymorphism, Genetic Delayed-Action Preparations Funding Source P-Value Data Analysis Software Analysis of Variance Phenotype Human Male Female Young Adult Adult Middle Age Body Mass Index Paroxetine Blood Adult: 19-44 years Middle Aged: 45-64 years Male Female ab: Purpose: This study evaluated the effects of cytochrome P450 (CYP) 2D6 polymorphisms on the pharmacokinetics of controlled-release paroxetine in healthy Chinese subjects and used paroxetine as a tool drug to compare the performance of traditional phenotype and activity score systems. Methods: Pharmacokinetic data were evaluated in 24 subjects who received a single oral dose of 25 mg controlled-release paroxetine. Plasma paroxetine concentrations were measured by LC-MS/MS. CYP2D6 genotypes were tested by PCR and direct DNA sequencing. Subjects were classified by two systems of phenotype prediction. In the traditional phenotype system, subjects were classified as extensive metabolizers or intermediate metabolizers; in the activity score system, subjects were divided into four activity groups. Analysis of variance testing was applied to estimate the effects of CYP2D6 polymorphisms on the pharmacokinetics of paroxetine. Results: With the traditional phenotype system, significant differences were observed in the following pharmacokinetic parameters of paroxetine: t, C, AUC, AUC, V/F, and CL/F (all P < 0.05). The AUC or exposure of paroxetine was about 3.5-fold higher in the intermediate metabolizer group than in the extensive metabolizer group. With the activity score system, significant differences were observed in the t, C, AUC, AUC, V/F, and CL/F among the four different activity score groups (all P < 0.05). We found that the AUC of paroxetine decreased by around one half as the activity score increased by 0.5. Conclusion: The pharmacokinetics of controlled-release paroxetine after a single administration was affected by CYP2D6 polymorphisms. Both the traditional phenotype and the activity score systems performed well and distinguished subjects with different drug exposures. The activity score system provided a more detailed classification for the subjects. pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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