Background: In immunosuppressive therapy administered after organ transplantation, therapeutic drug monitoring (TDM) of tacrolimus must be performed frequently because of the large variation in its pharmacokinetic properties and a progressive decrease in dose requirements. An indicator for estimating the target minimum whole-blood tacrolimus concentration (C min TAC) would be useful to minimize the number of blood samplings required for tacrolimus TDM. Objectives: The primary objective of this study was to investigate whether plasma prednisolone concentration, postoperative days (POD) and AUC 0 to 9 hours before transplantation (AUC 0–9int) are useful indicators of tacrolimus TDM. The secondary objective was to determine the usefulness of blood tacrolimus concentration as an indicator of the development of nontraumatic, glucocorticoid-induced necrosis of the femoral head, an adverse event that has been associated with the use of prednisolone in vivo. Methods: This open-label, nonrandomized, retrospective study was conducted at the Department of Transplantation and Regenerative Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan. Data from 43 male and 22 female patients (mean age, 38 years [range, 9–64 years]) who received a living-related kidney transplant from 2001 to 2004 were included. Multiple blood samplings were performed to determine AUC 0–9int, AUC 0 to 9 hours after drug administration and after transplantation (AUC 0–9), C min TAC, C max, and T max after transplantation. The correlations between each parameter were determined. The correlation between POD and the changes in tacrolimus bioavailability was investigated using the indicator, defined as the tacrolimus dose required to maintain the target (10–15 ng/mL) C min TAC (dose/C 10–15). Correlations between dose/C 10–15 and AUC 0–9int (3 AUC 0–9int groups, defined as follows: low, medium, and high [<93, ≧93−≤152, and ≧152 ng·h/mL, respectively]) were determined. Correlations between mean C min values of prednisolone at a dose of 40 mg on PODs 4 to 11 (C min PSL40) and C min TAC, or AUC 0–9int were determined. A subanalysis was used to determine the relationship between dose/C 10–15 and the prevalence of nontraumatic, glucocorticoid-induced necrosis of the femoral head. Results: C min TAC was found to be significantly correlated with AUC 0–9int ( r=0.554; P<0.001) and C min PSL40 ( r=0.336; P<0.001). In the low-AUC 0–9int group, dose/C 10–15 was higher than that of the other groups ( P<0.001). AUC 0–9int was significantly correlated with C min PSL40 ( r=0.445; P<0.001)). Dose/C 10–15 in the patient group that had necrosis of the femoral head was lower than that of the group without necrosis (n=6; P<0.01). Conclusions: The results of this small, retrospective study suggest that C min PSL40, AUC 0–9int, and POD were significant predictors of C min TAC. These parameters were found to be a useful indicator of tacrolimus TDM in these Japanese transplant recipients. Our results also suggest that dose/C 10–15 and AUC 0–9int might be useful indicators for estimating the risk for nontraumatic, steroid-induced necrosis of the femoral head. ( Curr Ther Res Clin Exp. 2006;67: 103–117) Copyright © 2006 Excerpta Medica, Inc.