Importance of using a pharmacogenetic approach to predict individual pharmacokinetics and safety profile of apixaban

In recent years, there has been a trend towards increased prescribing of direct-acting oral anticoagulants (DOACs) due to favourable pharmacokinetics and pharmacodynamics without the need for regular coagulation monitoring. However, recent studies have documented individual variability in plasma DOAC levels. DOAC pharmacogenetics is a relatively new area of research. There is a need to understand the role of pharmacogenetics in the adaptation of anticoagulant therapy according to a patient’s genetic characteristics. This scientific review of current data on the impact of different gene polymorphisms on apixaban pharmacokinetics broadens the understanding of the clinical relevance of genotyping for treatment efficacy and safety.

Using pharmacokinetics to individualize hemophilia therapy

Prevention and treatment of bleeding in hemophilia requires that plasma clotting factor activity of the replaced factor exceeds a defined target level. Most clinical decisions in hemophilia are based on implicit or explicit application of pharmacokinetic measures. The large interindividual variability in pharmacokinetics of factor concentrates suggests that relying on the average pharmacokinetic characteristics of factor concentrates would not allow optimizing the treatment of individual patients; for example, adjusting the frequency of infusions and targeting a specific clotting factor activity level on a case-by-case basis. However, individual pharmacokinetic profiles are seldom assessed as part of routine clinical care. Population pharmacokinetics provide options for precise and convenient characterization of pharmacokinetics characteristics of factor concentrates, simplified individual pharmacokinetic profiling, and individualized dosing. Population pharmacokinetics allow for the incorporation of determinants of interpatient variability and reduces the need for extensive postinfusion plasma sampling. Barriers to the implementation of population pharmacokinetics are the need for concentrate-specific pharmacokinetic models, Bayesian calculation power, and specific expertise for production, validation, and appraisal of forecasted estimates. Population pharmacokinetics provide an important theoretical and practical contribution to tailoring the treatment of hemophilia. The need remains for prospective exploration of the clinical impact of tailoring hemophilia treatment based on individual pharmacokinetics, and for the systematic validation of existing software solutions and concentrate-specific models.

Therapeutic Drug Monitoring in Rheumatic Diseases

The ultimate goal of treating rheumatic disease is to achieve rapid suppression of inflammation, while at the same time minimizing the toxicities from rheumatic drugs. Different patients have different individual pharmacokinetics that can affect the drug level. Moreover, different factors, such as renal function, age or even different underlying diseases, can affect the drug level. Therefore, giving the same dosage of drugs to different patients may result in different drug levels. This article will review the usefulness of therapeutic drug monitoring in maximizing drug efficacy, while reducing the risk of toxicities in Hydroxychloroquine, Mycophenolate Mofetil, Tacrolimus and Tumor Necrosis Factor inhibitors (TNF Inhibitors).