CLINICAL IMMUNOSUPPRESSION - KIDNEY EARLY

K. Yoshida¹, M. Kobayashi², D. Ishii¹, Y. Takeuchi³, H. Wakai¹, R. Maeyama¹, D. Koguchi¹, K. Yago², S. Baba^1
1Urology, Kitasato University, Sagamihara/JAPAN, ²Pharmacy, Kitasato University Hospital, Sagamihara/JAPAN, ³Nephrology, Kitasato University, Sagamihara/JAPAN

Body: Purpose: Once-daily extended-release formulation of tacroloimus (TER) has been developed to decrease nephrotoxitciy with Cmax and incompliance. It has been reported that TER has a similar efficacy and safety profile to twice-daily tacrolimus (TAC) in American clinical trials. We compared pharmacokinetics of TER and TAC in de novo kidney transplantation (RT) in Japanese population. Methods: Twelve renal transplantation using TER were analyzed pharmacokinetics of tacrolimus and the characteristics of the donor and recipients, rejection and adverse events. All patients received TER (0.2mg/kg), corticosteroids, mycofenolate mofetil and basiliximab. There data were compared to other 10 RT using TAC. Pharmacokinetic (PK) study was performed by blood sampling at 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 18 hours after TER or TAC taking. PK study was done before and 7, 14, 28 days and 3 months after the transplantation. Results: The mean age of RT patients with TER was 50(13-65) year old, and six of them were male recipients. All patients were first transplant. Ten patients received kidney from living donor, and two from deceased donor. The mean dose of TER was 0.20mg/kg (0.11-0.33) during 1 week to 12 weeks after transplant, to achieve target blood levels according to our protocol. The mean serum creatinine was 3.2mg/dl, 1.75mg/dl and 1.58mg/dl at 7 days, 1 month, and 3 months after transplant respectively. The mean tacrolimus blood trough level (C₀) were 11.4ng/ml (day7), 7.7 (day14), 12.3 (day21), 12.6 (day28), 8.8 (2 months) and 7.7(3 months). The average AUC_0-24 of tacrolimus were 372.0 ng/ml hr (day7), 323.5 (day14), 439.7 (day21), and 377.0 (day28). Correlation between C₀ and AUC_0-24 was excellent (r=0.88). Blood concentration/(dose/BW) ratio of tacrolimus tended to be lower between 7 and 21days after transplant using TER. We experienced no acute rejection in these 12 RT, but five patients (42%) received anti-CMV therapy due to positive CMV antigenemia during 2-6 weeks after transplant with TER. Conclusion: These data indicates that TER is similarly safe and effective to TAC, but necessary to pay some pharmacokinetic attention during 2-3 weeks post de novo renal transplantation.

Disclosure: All authors have declared no conflicts of interest.