These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: A PK-PD model for predicting the impact of age, CYP2C9, and VKORC1 genotype on individualization of warfarin therapy.
    Author: Hamberg AK, Dahl ML, Barban M, Scordo MG, Wadelius M, Pengo V, Padrini R, Jonsson EN.
    Journal: Clin Pharmacol Ther; 2007 Apr; 81(4):529-38. PubMed ID: 17301738.
    Abstract:
    The aim of this study was to characterize the relationship between warfarin concentrations and international normalized ratio (INR) response and to identify predictors important for dose individualization. S- and R-warfarin concentrations, INR, and CYP2C9 and VKORC1 genotypes from 150 patients were used to develop a population pharmacokinetic/pharmacodynamic model in NONMEM. The anticoagulant response was best described by an inhibitory E(MAX) model, with S-warfarin concentration as the only exposure predictor for response. Delay between exposure and response was accounted for by a transit compartment model with two parallel transit compartment chains. CYP2C9 genotype and age were identified as predictors for S-warfarin clearance, and VKORC1 genotype as a predictor for warfarin sensitivity. Predicted INR curves indicate important steady-state differences between patients with different sets of covariates; differences that cannot be foreseen from early INR assessments alone. It is important to account for CYP2C9 and VKORC1 genotypes and age to improve a priori and a posteriori individualization of warfarin therapy.
    [Abstract] [Full Text] [Related] [New Search]