Strategies for individualized dosing of clotting factor concentrates and desmopressin in hemophilia A and B

Therapeutic Drug Monitoring
Tim PreijersRon A A Mathôt

Abstract

Hemophilia A and B are hereditary bleeding disorders, caused by a deficiency of clotting factor VIII or clotting factor IX, respectively. To treat and prevent bleedings, patients can administer clotting factor concentrates (hemophilia A and B) or desmopressin (hemophilia A). Both clotting factor concentrates and desmopressin are currently dosed according to the patients' body weight. However, clotting factor concentrates exhibit considerable pharmacokinetic (PK) variability. Therefore, several alternative dosing strategies to individualize dosing of clotting factor concentrates and desmopressin in hemophilia A and B have been proposed. In this study, a review of the existing literature on the individualization of dosing based on PK-guidance was performed. In total, 79 articles were included. The methods to individualize dosing were divided into three categories: (i) methods using clinical parameters, (ii) empirical individual PK-guided methods, and (iii) maximum a posteriori (MAP) Bayesian estimation methods. The clinical parameter mainly used to individualize dosing is bleeding phenotype. Dosing based on bleeding phenotype may decrease clotting factor consumption. However, with this method, it is not possible to individualize ...Continue Reading

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Sep 17, 2020·Clinical Pharmacokinetics·Tim PreijersRon A A Mathôt

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