Determinants of the Over-Anticoagulation Response during Warfarin Initiation Therapy in Asian Patients Based on Population Pharmacokinetic-Pharmacodynamic Analyses

Minami Ohara, Harumi Takahashi, Ming Ta Michael Lee, Ming-Shien Wen, Tsong-Hai Lee, Hui-Ping Chuang, Chen-Hui Luo, Aki Arima, Akiko Onozuka, Rui Nagai, Mari Shiomi, Kiyoshi Mihara, Takashi Morita and Yuan-Tsong Chen

PLOS ONE, 2014, vol. 9, issue 8, 1-11

Abstract: : To clarify pharmacokinetic-pharmacodynamic (PK-PD) factors associated with the over-anticoagulation response in Asians during warfarin induction therapy, population PK-PD analyses were conducted in an attempt to predict the time-courses of the plasma S-warfarin concentration, Cp(S), and coagulation and anti-coagulation (INR) responses. In 99 Chinese patients we analyzed the relationships between dose and Cp(S) to estimate the clearance of S-warfarin, CL(S), and that between Cp(S) and the normal prothrombin concentration (NPT) as a coagulation marker for estimation of IC50. We also analyzed the non-linear relationship between NPT inhibition and the increase in INR to derive the non-linear index λ. Population analyses accurately predicted the time-courses of Cp(S), NPT and INR. Multivariate analysis showed that CYP2C9*3 mutation and body surface area were predictors of CL(S), that VKORC1 and CYP4F2 polymorphisms were predictors of IC50, and that baseline NPT was a predictor of λ. CL(S) and λ were significantly lower in patients with INR≥4 than in those with INR

Date: 2014
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Persistent link: https://EconPapers.repec.org/RePEc:plo:pone00:0105891

DOI: 10.1371/journal.pone.0105891

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