Metabolic Drug Interactions with Immunosuppressants

Abstract

Organ transplantation has become a routine clinical practice for patients with end- stage disease of liver, kidney, heart, or lung. Although improved immunosuppressant therapy substantially contributes to the success of transplantation, clinicians continue to face challenges because of wide interindividual variations in blood concentrations resulting in subtherapeutic or supratherapeutic levels. Many undesired side-efects or therapeutic failure of immunosuppressants as a consequence are the results of difer- ences or changes in drug metabolism. Considering genetic and nongenetic factors, such as co-medication, can reine the immunosuppressant therapy, facilitating personalized treatments to individual recipients. This review provides an up-to-date summary of functional polymorphisms of enzymes involved in the metabolism of immunosuppres- sants with low molecular weight and of the clinical signiicance of metabolic drug inter- actions between immunosuppressive agents and other drugs in therapeutic regimens of transplant recipients. Keywords: drug metabolism, genetic polymorphism, phenoconversion, calcineurin inhibitors, mTOR inhibitors, corticosteroids, inosine monophosphate dehydrogenase inhibitors 1.