Pharmacogenetics of immunosuppressant drugs: A new aspect for individualized therapy

Abstract

In recent years, pharmacogenetics has emerged as an important tool for choosing the right immunosuppressant drug and its appropriate dose. Indeed, pharmacogenetics may exert its action on immunosuppressant drugs at three levels. Pharmacogenetics identifies and studies the genes involved in encoding the proteins involved in drug pharmacokinetics and in encoding the enzymes involved in drug degradation. Pharmacogenetics is also relevant in encoding the enzymes and proteins involved in codifying the transmembrane proteins involved in transmembrane passage favoring the absorption and intracellular action of several immunosuppressants. Pharmacogenetics concern the variability of genes encoding the proteins involved as immunosuppressant triggers in the pharmacodynamic pathways. Of course, not all genes have been discovered and studied, but some of them have been clearly examined and their relevance together with other factors such as age and race has been defined. Other genes on the basis of relevant studies have been proposed as good candidates for future studies. Unfortunately, to date, clear conclusions may be drawn only for those drugs that are metabolized by CYP3A5 and its genotyping before kidney, heart and lung transplantation is recommended. The conclusions of the studies on the recommended candidate genes, together with the development of omics techniques could in the future allow us to choose the right dose of the right immunosuppressant for the right patient.

Keywords: Immunosuppressant pharmacokinetics; Immunosuppressant pharmacodynamics; Immunosuppressant pharmacogenetics; Immunosuppressant pharmacogenomics; Transplantation; Immunosuppressant drugs

Core tip: The most common factors associated with drug response include age, sex, ancestry, concomitant drugs and liver or kidney diseases and drug pharmacogenetics. In general pharmacogenetics is the study of the variability of the response of a drug related to the complex gene arrays. More recently, the term pharmacogenomics has been introduced. This term in particular is related to omics studies. In recent years, pharmacogenetics that evaluates the drug response to genetic variations has emerged as an important tool for choosing the right therapeutic dose. According to the aim of the Precision Medicare Initiative, pharmacogenomics may contribute to providing the right drug at the right dose for the right patient.