Modelling the atypical absorption of menatetrenone and the metabolism to its epoxide: effect of VKORC1 polymorphism.
This study aimed to model the atypical absorption of menatetrenone and its epoxide metabolite and to examine the influence of the single nucleotide polymorphism (SNP) of vitamin K2 epoxide reductase complex subunit 1 (VKORC1) on the pharmacokinetics. After the administration of 30 mg of menatetrenon...
| Publicado en: | Journal of Clinical Pharmacy & Therapeutics Vol. 36; no. 3; pp. 390 - 399 |
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| Autores principales: | , , , , |
| Formato: | equations & formulas pictorial research tables/charts Journal Article |
| Publicado: |
Wiley-Blackwell
Jun2011
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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=104893170&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 104893170 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 02694727 EV4 jtl: Journal of Clinical Pharmacy & Therapeutics issn: 02694727 maglogo: Y pubinfo: dt: Jun2011 vid: 36 iid: 3 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 104893170 60419315 10.1111/j.1365-2710.2010.01183.x NLM21545618 104893170 ppf: 390 ppct: 9 formats: fmt: @attributes: type: P tig: atl: Modelling the atypical absorption of menatetrenone and the metabolism to its epoxide: effect of VKORC1 polymorphism. aug: au: Baek, I. H. Kang, W. Yun, H. Y. Lee, S. S. Kwon, K. I. affil: College of Pharmacy, Chungnam National University, Daejeon sug: subj: Polymorphism, Genetic Vitamin K Pharmacokinetics Vitamin K Blood Models, Biological Vitamin K Administration and Dosage Vitamin K Metabolism Mass Spectrometry Methods Genotype Human Male South Korea Descriptive Statistics Young Adult Adult Chromatography, High Pressure Liquid Linear Regression Intestinal Absorption Polymerase Chain Reaction Mann-Whitney U Test Biological Availability Funding Source Adult: 19-44 years Male ab: This study aimed to model the atypical absorption of menatetrenone and its epoxide metabolite and to examine the influence of the single nucleotide polymorphism (SNP) of vitamin K2 epoxide reductase complex subunit 1 (VKORC1) on the pharmacokinetics. After the administration of 30 mg of menatetrenone to 26 healthy subjects, the plasma concentrations of menatetrenone and its epoxide were measured using LC-MS/MS. For the haplotype analysis, the SNP of the VKORC1 gene was investigated in the 26 volunteers. The model parameters were estimated using the ADAPT II program. A two-compartment model with Weibull-type absorption and saturable elimination described the pharmacokinetics of menatetrenone and its epoxide. The plasma concentrations of both tended to be lower in the H1/H7 genotype group than in the wild-type H1/H1 group. We present the first detailed pharmacokinetic modelling of menatetrenone in relation to VKORC1 genotype. This study suggests that VKORC1 genotype is unlikely to be helpful in dose-selection because of the very high inter-individual variation in systemic exposure within each genotype group, and the small inter-group difference observed. pubtype: Academic Journal doctype: equations & formulas pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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