Correlation of tacrolimus concentrations with AUC according to C/D ratio-based metabolizer status in kidney transplant recipients.

초록

Introduction: Therapeutic drug monitoring (TDM) of tacrolimus is traditionally based on trough concentration (C0), although area under the concentration–time curve (AUC) more accurately reflects drug exposure. This study evaluated the correlation between tacrolimus concentrations at different time points (C0, C2, and C4) and AUC, and analyzed differences according to metabolizer status. Methods: A total of 24 kidney transplant recipients were included, and tacrolimus levels were measured using a three-point sampling strategy. Individual AUC₀–₂₄ values were estimated using a Bayesian approach (MW Pharm®). The concentration/dose (C/D) ratio was calculated as tacrolimus trough concentration (ng/mL) divided by the total daily dose (mg/day). To enhance discrimination between metabolizer phenotypes, patients with intermediate C/D ratios (1.5–2.0) were excluded. The remaining patients were classified as fast metabolizers (C/D < 1.5) and slow metabolizers (C/D > 2.0). Correlations between tacrolimus concentrations and AUC were analyzed within each group. Results: Tacrolimus concentrations at C0, C2, and C4 were all significantly correlated with AUC (all p < 0.001), with C4 showing the strongest overall correlation. In subgroup analysis, C4 demonstrated particularly strong correlation with AUC in fast metabolizers (r = 0.938), compared with C0 (r = 0.867) and C2 (r = 0.823). In slow metabolizers, correlations were comparable across time points. Conclusions: C0, C2, and C4 all showed good correlation with AUC and may serve as useful surrogate markers for tacrolimus dose adjustment. Notably, C4 demonstrated particularly strong correlation with AUC in fast metabolizers, suggesting its potential utility as an optimal sampling point in this subgroup. Further studies with larger cohorts are warranted to validate these findings.