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Semi-empirical anticoagulation model (SAM): INR monitoring during Warfarin therapy

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Abstract

The International Normalized Ratio (INR) monitoring is an essential component to manage thrombotic disease therapy. This study presents a semi-empirical model of INR as a function of time and assigned therapy (Warfarin, k-vitamin). With respect to other methodologies, this model is able to describe the INR using a limited number of parameters and is able to describe the time variation of INR described in the literature. The presented methodology showed great accuracy in model calibration [(trueness (precision)]: 0.2% (0.1%) to 1.2% (0.3%) for coagulation factors, from 5% (9%) to 9.7% (12%) for Warfarin-related parameters and 38% (40%) for K-vitamin-related parameters. The latter value was considered acceptable given the assumptions made in the model. It has two other important results: the first is that it was able to correctly estimate INR with respect to daily therapy doses taken from the literature. The second is that it introduces a single numeric semi-empirical parameter that is able to correlate INR/dose response to physiological and environmental condition of patients.

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Acknowledgements

I would like to thank Dr. Maria Paola Landini and Dr. Milena Fini for their support and encouragement in the preparation of this work. I would also like to thank Eng. Gregorio Marchiori for valuable feedback on the writing of the manuscript. Lastly, my wife my son for ideas and motivation.

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    Marco Bontempi

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Bontempi, M. Semi-empirical anticoagulation model (SAM): INR monitoring during Warfarin therapy. J Pharmacokinet Pharmacodyn 49, 271–282 (2022). https://doi.org/10.1007/s10928-021-09783-8

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