Comparative pharmacokinetics of tacrolimus in stable pediatric allograft recipients converted from immediate-release tacrolimus to prolonged-release tacrolimus formulation
Abstract
This study was a Phase II, open-label, multicenter, single-arm, cross-over study comparing the pharmacokinetics (PK) of tacrolimus in stable pediatric kidney, liver, or heart allograft recipients converted from immediate-release tacrolimus (IR-T) to prolonged-release tacrolimus (PR-T). In Days -30 to -1 of screening period, patients received their IR-T-based regimen; during Days 1-7, patients received study IR-T (same dose as screening).
On Day 7, the first 24-hours PK profile was taken; patients were then converted to PR-T (1 mg:1 mg), with a second 24-hours PK profile taken on Day 14. The primary end-point was tacrolimus area under the blood concentration-time curve over 24 hours (AUC(24)); secondary end-points were maximum concentration C(max)and concentration at 24 hours C-24.
The predefined similarity interval for confidence intervals (CIs) of least squares mean (LSM) ratios was 80%-125%. The PK analysis set comprised 74 pediatric transplant recipients (kidney, n = 45; liver, n = 28; heart, n = 1).
PR-T:IR-T LSM ratio (90% CI) was similar overall for AUC(24), (max), and C-24, and for kidney and liver recipients for AUC(24) (LSM ratio, kidney 91.8%; liver 104.1%) and C-24 (kidney 90.5%; liver 89.9%). Linear relationship was similar between AUC(24) and C-24, and between PR-T and IR-T (rho 0.89 and 0.84, respectively), suggesting that stable pediatric transplant recipients can be converted from IR-T to PR-T at the same total daily dose, using the same therapeutic drug monitoring method.