Pharmacogenetics and tacrolimus administration in stem cell transplantation

Abstract

Tacrolimus is the gold standard immunosuppressant administered in solid organ and stem cell transplantation to avoid graft rejection post-transplant. Despite its widespread use, there is a large variation in response to therapy, likely due to high inter-individual pharmacokinetic variability. Therapeutic drug monitoring is employed to improve clinical response and reduce toxicity. There is substantial evidence that pharmacogenetics influences drug exposure and response. CYP3A5 genotype significantly impacts oral tacrolimus concentrations and response after solid organ transplantation. There are fewer studies in stem cell transplantation and with intravenous tacrolimus dosing. This report highlights recent evidence suggesting genes such as CYP3A4 and ABCB1 play a larger role after intravenous dosing compared with CYP3A5, and the role for novel genes on tacrolimus outcomes.