Aims: Few data is available regarding the pharmacokinetic (Pk) profile of newly developed modified-release once-daily formulation of tacrolimus (MR-Tac) in children. This study investigated Pk differences between MR-Tac and the original formulation requiring twice-daily intake (Tac) in de novo pediatric kidney transplant recipients.

Methods: Twenty-four pediatric patients who received a kidney allograft between April 2010 and November 2012 were enrolled. According to our current immunosuppressive protocol, Tac was converted to MR-Tac 2 weeks after the transplantation. The switch dose ratio was 1:1, and the 24hours full Pk study of each formulation was assessed.

Results: The mean age at transplantation was 12.0 ± 3.6 years (range 5.0-21.6) with 14 males and 10 females. The mean total daily dose at baseline upon conversion was 5.0 ± 2.8 mg (0.18 ± 0.11 mg/kg body weight).

The Pk parameter of each formulation was shown in the table. There was no difference in the mean maximum concentration (Cmax), the mean time to maximum concentratuion (Tmax) and the mean area under the concentration-time curve (AUC0-24) for Tac and MR-Tac. However, the trough concentration (C0) of tacrolimus was approximately 18% lower for MR-Tac than Tac.

Moreover, a better correlation was observed between the AUC0-24 and C0 for MR-Tac than Tac (r²=0.879, P<0.001 in MR-Tac vs. r²=0.627, P<0.001 in Tac, respectively) and a similar coefficient in each regression equation.

Conclusions: Co-guided therapeutic drug monitoring of MR-Tac is effective even in pediatric kidney transplant recipients. However, the target trough level should be arranged because the C0 of tacrolimus was approximately 18% lower for MR-Tac than Tac to obtain the same AUC0-24.²

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