Modelling the atypical absorption of menatetrenone and the metabolism to its epoxide: effect of VKORC1 polymorphism.
Level 4 - case-series / case-control
Single-arm pharmacokinetic and pharmacogenetic study in healthy volunteers
PubMed 21545618 · doi:10.1111/j.1365-2710.2010.01183.x
What was done
Twenty-six healthy volunteers were administered a single 30 mg dose of menatetrenone. Plasma concentrations of menatetrenone and its epoxide metabolite were measured via LC-MS/MS, and participants were genotyped for single nucleotide polymorphisms in the VKORC1 gene (evaluating H1/H1 wild-type vs. H1/H7). Pharmacokinetic parameters were modeled using the ADAPT II program.
What was found
A two-compartment model featuring Weibull-type absorption and saturable elimination successfully described the pharmacokinetics. Plasma concentrations of menatetrenone and its epoxide metabolite tended to be lower in the H1/H7 genotype group compared to the wild-type H1/H1 group. The abstract did not report numerical values, effect sizes, or p-values.
Why it matters
This provides a structural pharmacokinetic model for menatetrenone absorption and metabolism, while indicating that VKORC1 genotyping is unlikely to be clinically useful for dose individualization due to high inter-individual variation.
Limits
The sample size was small (n = 26 healthy subjects) and the abstract lacks quantitative pharmacokinetic parameters and statistical testing details. As a single-dose study in healthy subjects, findings may not generalize to chronic dosing or clinical populations.
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