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A Limited Sampling Strategy to Estimate the Area Under the Concentration-Time Curve of Tacrolimus Modified-release Once-daily Preparation in Renal Transplant Recipients

Objectives: The aim of this study was to develop a limited sampling strategy to estimate the area under the concentration-time curve (AUC) of a modified-release, once-daily formulation of tacrolimus (Advagraf, Japanese trade name Graceptor) with Japanese renal transplant patients. Methods: Among the 43 enrolled patients, 23 patients continued to take Graceptor for 1 year. A total of 66 profiles on day 28 and day 365 from the 43 patients were randomly divided into a training group (N = 33) and a validation group (N = 33) without any overlap. Results: The prediction formula for the AUC0–24 using the single C12h time point gave the highest correlation with the observed AUC0–24 (r2 = 0.9057). When 2 sampling times were used, C0h–C12h were the best time points for the estimation of the AUC0–24 (AUC0–24 = 26.8 + 8.0C0h + 17.8C12h, r2 = 0.9221, P < 0.0001). There was no significant difference in the prediction error for the prediction formulas with the C0h–C12h combination between CYP3A5 genotypes. The % mean prediction error, % mean absolute error, and % root mean squared prediction error of the prediction formula using C0h–C12h were 0.1%, 7.6%, and 8.8%, respectively. Conclusions: In a hospital setting, a limited sampling strategy using C0h–C12h would be applicable to estimating the AUC0–24 of tacrolimus once daily.