caa a22 4500 445313854 CHVBK 20180317142639.0 cr unu---uuuuu 170323e20110501xx s 000 0 eng 10.1007/s11095-011-0369-x doi (NATIONALLICENCE)springer-10.1007/s11095-011-0369-x Development of a Bayesian Forecasting Method for Warfarin Dose Individualisation [Elektronische Daten] [Daniel Wright, Stephen Duffull] ABSTRACT: Purpose: The aim of this study was to develop a Bayesian dose individualisation tool for warfarin. This was incorporated into the freely available software TCIWorks (www.tciworks.info) for use in the clinic. Methods: All pharmacokinetic and pharmacodynamic (PKPD) models for warfarin in the medical literature were identified and evaluated against two warfarin datasets. The model with the best external validity was used to develop an optimal design for Bayesian parameter control. The performance of this design was evaluated using simulation-estimation techniques. Finally, the model was implemented in TCIWorks. Results: A recently published warfarin KPD model was found to provide the best fit for the two external datasets. Optimal sampling days within the first 14days of therapy were found to be days 3, 4, 5, 11, 12, 13 and 14. Simulations and parameter estimations suggested that the design will provide stable estimates of warfarin clearance and EC50. A single patient example showed the potential clinical utility of the method in TCIWorks. Conclusions: A Bayesian dose individualisation tool for warfarin was developed. Future research to assess the predictive performance of the tool in warfarin patients is required. Springer Science+Business Media, LLC, 2011 anticoagulation nationallicence optimal design nationallicence population pharmacokinetic-pharmacodynamic modelling nationallicence therapeutic drug monitoring nationallicence warfarin nationallicence BSV : between-subject variability nationallicence CL : clearance nationallicence CYP : cytochrome P450 nationallicence diag : diagonal nationallicence EC50 : the drug concentration at 1/2 of maximum effect nationallicence FIM : Fisher information matrix nationallicence INR : international normalised ratio nationallicence J : Jacobian matrix nationallicence KPD : kinetic-pharmacodynamic nationallicence MAP : maximum a posterior nationallicence MTT : mean transit time nationallicence PCA : prothrombin complex activity nationallicence PKPD : pharmacokinetic-pharmacodynamic nationallicence PT : prothrombin time nationallicence RSE : relative standard error nationallicence RUV : residual unexplained variability nationallicence SE : standard error nationallicence VKORC1 : vitamin K epoxide reductase nationallicence VPC : visual predictive check (external [e] or internal [i]) nationallicence Wright Daniel School of Pharmacy, University of Otago, PO Box56, 9054, Dunedin, New Zealand aut Duffull Stephen School of Pharmacy, University of Otago, PO Box56, 9054, Dunedin, New Zealand aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/5(2011-05-01), 1100-1111 0724-8741 28:5<1100 2011 28 11095 https://doi.org/10.1007/s11095-011-0369-x text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-011-0369-x text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Wright Daniel School of Pharmacy, University of Otago, PO Box56, 9054, Dunedin, New Zealand aut NATIONALLICENCE 700 1- Duffull Stephen School of Pharmacy, University of Otago, PO Box56, 9054, Dunedin, New Zealand aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/5(2011-05-01), 1100-1111 0724-8741 28:5<1100 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer