Strategies for Individualized Dosing of Clotting Factor Concentrates and Desmopressin in Hemophilia A and B

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 3 categories: (1) methods using clinical parameters, (2) empirical individual PK-guided methods, and (3) 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 on-demand dosing during bleeding events or in the perioperative setting. Empirical individual PK-guided methods can be used both for prevention and treatment of bleedings. These methods include dose individualization using a nomogram and individualized in vivo recovery. In the perioperative setting, adjustment of the rate of continuous infusion can be applied to obtain a specific target level. The final category, MAP Bayesian estimation methods, relies on the availability of a population PK model. In total, 22 population PK models describing clotting factor concentrate or desmopressin dosing are currently available in literature. MAP Bayesian estimates can be used to calculate the individualized doses required to achieve or maintain a target level in every setting. The application of PK-guided and pharmacodynamic-guided dosing of clotting factor concentrates and desmopressin seems promising,...
Source: Therapeutic Drug Monitoring - Category: Drugs & Pharmacology Tags: Review Articles: Focus on Pharmacodynamic Drug Monitoring Source Type: research