Tacrolimus Concentration/Dose Ratio: A Tool for Guiding Tacrolimus Dosage Post-renal Transplantation

Background The calcineurin inhibitor, Tacrolimus (Tac), exhibits variable absorption and undergoes first-pass metabolism when administered orally. The narrow therapeutic window and individual variability of this immunosuppressive agent make therapeutic drug monitoring essential. We hypothesized that the Tac metabolism rate - defined as the blood concentration normalized by its daily dose (the C/D ratio) - is associated with post-renal transplant (RTx) function. Methodology A retrospective observational study was conducted including 40 RTx patients. Clinical reports from four follow-up ambulatory appointments at one, three, six, and 12 months were analyzed. Tac dose and its blood levels were used to calculate the Tac concentration/dose (C/D) ratio. Patients with a Tac C/D ratio <1.05 ng/mL x 1/mg and a C/D ratio >1.05 ng/mL x 1/mg were categorized as fast and slow metabolizers. Serum creatinine levels were compared between the two groups, and their association with the Tac C/D ratio was analyzed. Student's unpaired t-test and the Mann-Whitney U test were used to analyze the difference in the C/D ratio between the groups. Spearman correlation analysis was conducted to analyze the association of the C/D ratio with serum creatinine in both groups. A P-value of <0.05 was considered statistically significant. Results Fast metabolizers showed increased serum creatinine (P < 0.05), and the C/D ratio correlated with creatinine levels. ROC analysis used to identify fast metabolizers for the C/D ratio at three months had an area of 0.925 (P < 0.01). Conclusions The Tac C/D ratio can be used as an earlier diagnostic tool to predict the development of nephrotoxicity in RTx patients.