Comparative pharmacokinetics of tacrolimus in de novo pediatric transplant recipients randomized to receive immediate‐ or prolonged‐release tacrolimus. (24th October 2018)

• Record Type: Journal Article
• Authors: Vondrak, Karel; Dhawan, Anil; Parisi, Francesco; Grenda, Ryszard; Debray, Dominique; Marks, Stephen D.; Webb, Nicholas J. A.; Lachaux, Alain; Kazeem, Gbenga; Undre, Nasrullah
• Is Part Of: Pediatric transplantation. Volume 22:Number 8(2018)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2018-10-24
• Subjects: heart transplantation -- kidney transplantation -- liver transplantation -- pediatrics -- pharmacokinetics -- tacrolimus; Transplantation of organs, tissues, etc. in children -- Periodicals; 617.95408305
• DOI: 10.1111/petr.13289
• Languages: English
• ISSNs: 1397-3142

Abstract

Abstract: 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 AUC24 . 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, AUC24 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 AUC24 ; 66.3%, 82.2%, 90.9% for C 24 ; and 77.3%, 120.3%, 92.2% for C max . AUC24 90% CI within predefined similarity interval on Day 28; other 90% CIs fell outside. Linear relationship was similar between AUC24 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.