Intrapatient Variability of Tacrolimus Exposure in Solid Organ Transplantation: A Novel Marker for Clinical Outcome

Abstract

The calcineurin-inhibitor tacrolimus (Tac) provides an acceptable balance between prevention of allograft rejection and drug-related adverse effects, making it the standard of care in all types of solid organ transplantation for the last 2 decades. Recent data have demonstrated that high intrapatient variability (IPV) in Tac predose trough concentrations has deleterious effects on allograft survival. The underlying mechanisms by which a high Tac IPV shortens allograft survival are acute and chronic rejection, donor-specific anti-HLA antibodies, and progressive fibrotic damage to the graft. Modifiable causes of high Tac IPV include medication nonadherence (MNA), drug interactions, nutritional interferences, and concurrent diseases. Recognizing high Tac IPV as an important prognostic risk factor after solid organ transplantation requires understanding of the definitions, the use of correct diagnostic metrics, and methodology. Therapeutic interventions aimed at reducing Tac IPV are targeted on improving MNA, avoiding or adjusting drug interactions, drug dosing assists, and educational support of recipients.