Model-based individualized treatment

Siv Jönsson, Mats Karlsson, Elisabet Nielsen

Large unexplained inter-patient variability in pharmacokinetics (PK) and pharmacodynamics (PD) may be a cause for suboptimal treatment in the individual patient. We aim to facilitate the use of and advance the methodologies for model-based treatment individualization using therapeutic drug monitoring (TDM) data. Ongoing projects relate to dose individualization of antibiotics in critically ill patients and factor VIII replacement therapy in hemophilia A patients.

Intensive care units (ICU) has a high prevalence of infections and a vulnerable and heterogeneous patient population. ICU patients exhibit extreme PK variability resulting in wide variations in drug exposures. Furthermore, the causative organisms in the ICU show a large variability in drug susceptibility, accordingly the drug exposure to target also needs to be personalised. We aim to develop and evaluate novel methods for dose individualization of antibiotics based on PK and PD modelling with the ultimate goal to improve patient outcome and minimize the emergence of resistance in the ICU.

Hemophilia are genetic disorders impairing blood coagulation due to deficiency of coagulation factor VIII (hemophilia A) and IX (hemophilia B), whereof hemophilia A is the more common although rare: in Sweden 14 of 100 000 boys and men have hemophilia,  (80 % hemophilia A). In prophylactic treatment with factor VIII and IX, pharmacokinetic (PK) tailored dose individualization is promoted, and is indicated to reduce the total doses administered. However, extensive unexplained variability is present in the bleeding risk and there is a need to consider the bleeding phenotype when individualising the dose. We aim to develop model-based dose individualisation strategies/methods in haemophilia accounting for the patient’s PK and bleeding characteristics.