Modelling the atypical absorption of menatetrenone and the metabolism to its epoxide: effect of VKORC1 polymorphism

Title
Modelling the atypical absorption of menatetrenone and the metabolism to its epoxide: effect of VKORC1 polymorphism
Author(s)
백인환[백인환]강원구윤휘열[윤휘열]이상섭[이상섭]권광일[권광일]
Keywords
VITAMIN-K; REDUCTASE; HAPLOTYPES; GENE; ANTICOAGULATION; REQUIREMENTS; CARBOXYLASE; RESISTANCE; PROTEIN; HUMANS
Issue Date
201106
Publisher
WILEY-BLACKWELL
Citation
JOURNAL OF CLINICAL PHARMACY AND THERAPEUTICS, v.36, no.3, pp.390 - 398
Abstract
P>What is known and Objective: 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. Methods: 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. Results and Discussion: 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. What is new and Conclusion: 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.
URI
http://hdl.handle.net/YU.REPOSITORY/25085http://dx.doi.org/10.1111/j.1365-2710.2010.01183.x
ISSN
0269-4727
Appears in Collections:
약학대학 > 약학부 > Articles
Files in This Item:
There are no files associated with this item.
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE