Impacts of High Intra- and Inter-Individual Variability in Tacrolimus Pharmacokinetics and Fast Tacrolimus Metabolism on Outcomes of Solid Organ Transplant Recipients

• Main Authors: Charat Thongprayoon, Panupong Hansrivijit, Karthik Kovvuru, Swetha R. Kanduri, Tarun Bathini, Aleksandra Pivovarova, Justin R. Smith, Wisit Cheungpasitporn
• Format: Article
• Language: English
• Published: MDPI AG 2020-07-01
• Series: Journal of Clinical Medicine
• Subjects: tacrolimus; calcineurin inhibitors; FK506; transplantation; kidney transplantation; immunosuppression
• Online Access: https://www.mdpi.com/2077-0383/9/7/2193

Tacrolimus is a first-line calcineurin inhibitor (CNI) and an integral part of the immunosuppressive strategy in solid organ transplantation. Being a dose-critical drug, tacrolimus has a narrow therapeutic index that necessitates periodic monitoring to maintain the drug’s efficacy and reduce the consequences of overexposure. Tacrolimus is characterized by substantial intra- and inter-individual pharmacokinetic variability. At steady state, the tacrolimus blood concentration to daily dose ratio (C/D ratio) has been described as a surrogate for the estimation of the individual metabolism rate, where a low C/D ratio reflects a higher rate of metabolism. Fast tacrolimus metabolism (low C/D ratio) is associated with the risk of poor outcomes after transplantation, including reduced allograft function and survival, higher allograft rejection, CNI nephrotoxicity, a faster decline in kidney function, reduced death-censored graft survival (DCGS), post-transplant lymphoproliferative disorders, dyslipidemia, hypertension, and cardiovascular events. In this article, we discuss the potential role of the C/D ratio in a noninvasive monitoring strategy for identifying patients at risk for potential adverse events post-transplant.