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Comparative pharmacokinetics of tacrolimus in de novo pediatric transplant recipients randomized to receive immediate‐ or prolonged‐release tacrolimus
Author(s) -
Vondrak Karel,
Dhawan Anil,
Parisi Francesco,
Grenda Ryszard,
Debray Dominique,
Marks Stephen D.,
Webb Nicholas J. A.,
Lachaux Alain,
Kazeem Gbenga,
Undre Nasrullah
Publication year - 2018
Publication title -
pediatric transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.457
H-Index - 69
eISSN - 1399-3046
pISSN - 1397-3142
DOI - 10.1111/petr.13289
Subject(s) - tacrolimus , medicine , cmax , pharmacokinetics , confidence interval , clinical endpoint , gastroenterology , transplantation , urology , randomized controlled trial
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 CI s 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% CI s 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.