Comparative pharmacokinetics of tacrolimus in de novo pediatric transplant recipients randomized to receive immediate- or prolonged-release tacrolimus

Phase 2, parallel-group, multicenter, open-label, 4-week study, comparing PK of PR-T vs IR-T in de novo pediatric patients undergoing primary kidney, liver, or heart transplantation. Patients randomized 1:1 to receive once daily, PR-T-, or twice-daily, IR-T-based regimens; dose adjustments permitted after Day 1. Twenty-four-hour PK profiles collected on Days 1, 7, and 28. Primary endpoint: tacrolimus AUC(24). Secondary end points included tacrolimus C-24 and C-max. Endpoints compared between PR-T and IR-T on Days 1, 7, and 28. Predefined similarity interval for CIs of LSM ratios: 80%-125%. PK analysis set comprised 33 patients (PR-T, n = 15; IR-T, n = 18). Overall, AUC(24) and C-max were lower on Day 1 vs 7 and 28. Geometric LSM ratios of PR-T:IR-T on Days 1, 7, and 28 were 66.3%, 92.5%, 99.9%, respectively, for AUC(24); 66.3%, 82.2%, 90.9% for C-24; and 77.3%, 120.3%, 92.2% for C-max. AUC(24) 90% CI within predefined similarity interval on Day 28; other 90% CIs fell outside. Linear relationship was similar between AUC(24) and C-24, and between tacrolimus formulations, suggesting that the same therapeutic drug monitoring method can be used with both formulations in de novo pediatric allograft recipients