Background:Use of an appropriate immunosuppressant is necessary for good graft survival in kidney transplantation (KTx). Currently, a prolonged-release formulation of tacrolimus (Graceptor or Adovagraf, Astellas Pharma; TAC-ER) has been recently developed and widely used. In the clinical setting, trough concentration of TAC-ER (C0) was generally evaluated and the dosage of TAC-ER was adjusted. We previously reported the correlation between twenty-four hour area under the curve (AUC0-24) and C0, and found that C0 was well correlated with AUC0-24. However, the sample size studied was small (50 patients). Further, no other studies reported this correlation; therefore, the actual pharmacokinetics (PK) of TAC-ER is yet to be determined. Here, we evaluated the correlation between AUC0-24 and concentration of TAC-ER.

Methods: During the period between January 2011 and August 2015, 309 KTx recipients were enrolled in PK study and underwent renal biopsy on post-operative day 14 at our institution. Blood samples were collected at 10 time points (C0, C1-4, C12-16).

Results: AUC0-24≥250 ng[bull]h/mL was observed in 222 patients and AUC0-24≺250 was observed in 87 patients. There was a significant correlation between AUC0-4 and AUC0-24 (R2=0.6413). C4 was well correlated with AUC0-24 (R2=0.6759); however, C0 was less correlated with AUC0-24 (R2=0.2973). Renal biopsy showed that CNI toxicity was marked in the AUC0-24≥250 group compared to that in the ACU0-24<250 group.

Conclusions: C4 had a significant correlation with AUC0-24, indicating good concentration monitoring. This is the first report of the pharmacokinetics of TAC-ER in a large population.

CITATION INFORMATION: Unagami K, Okumi M, Furusawa M, Hirai T, Shimizu T, Omoto K, Inui M, Ishida H, Nitta K, Tanabe K. Pharmakokinetics of Prolonged-Release Formulation of Tacrolimus: Comparison of AUC0-24 and Concentration at 10 Time Points. Am J Transplant. 2016;16 (suppl 3).

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