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Once‐daily, prolonged‐release tacrolimus vs twice‐daily, immediate‐release tacrolimus in de novo living‐donor liver transplantation: A Phase 4, randomized, open‐label, comparative, single‐center study
Author(s) -
Shin MinHo,
Song GiWon,
Lee SungGyu,
Hwang Shin,
Kim KiHun,
Ahn ChulSoo,
Moon DeokBog,
Ha TaeYong,
Jung DongHwan,
Park GilChun,
Yun YoungIn,
Kim WanJun,
Kang WooHyoung,
Kim SeokHwan,
Jiang Hongsi,
Lee Sungmin,
Tak EunYoung
Publication year - 2018
Publication title -
clinical transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 76
eISSN - 1399-0012
pISSN - 0902-0063
DOI - 10.1111/ctr.13376
Subject(s) - medicine , tacrolimus , single center , clinical endpoint , liver transplantation , adverse effect , pharmacokinetics , confidence interval , transplantation , gastroenterology , incidence (geometry) , surgery , randomized controlled trial , urology , physics , optics
Randomized, open‐label, comparative, single‐center, Phase 4, 24‐week study comparing pharmacokinetics ( PK ), safety, and efficacy of once‐daily, prolonged‐release tacrolimus ( PR ‐T) with twice‐daily, immediate‐release tacrolimus ( IR ‐T) in adult de novo living‐donor liver transplant ( LDLT ) recipients in Korea. All patients received intravenous tacrolimus from Day 0 (transplantation) for 4 days and were randomized (1:1) to receive oral PR ‐T or IR ‐T from Day 5. PK profiles were taken on Days 6 and 21. Primary endpoint: area under the concentration‐time curve over 24 hour ( AUC 0‐24 ). Predefined similarity interval for confidence intervals of ratios: 80%‐125%. Secondary endpoints included: tacrolimus concentration at 24 hour (C 24 ), patient/graft survival, biopsy‐confirmed acute rejection ( BCAR ), treatment‐emergent adverse events ( TEAE s). One‐hundred patients were included ( PR ‐T, n = 50; IR ‐T, n = 50). Compared with IR ‐T, 40% and 66% higher mean PR ‐T daily doses resulted in similar AUC 0‐24 between formulations on Day 6 ( PR ‐T: IR ‐T ratio of means 96.8%), and numerically higher AUC 0‐24 with PR ‐T on Day 21 (128.8%), respectively. Linear relationship was similar between AUC 0‐24 and C 24 , and formulations. No graft loss/deaths, incidence of BCAR and TEAE s similar between formulations. Higher PR ‐T vs IR ‐T doses were required to achieve comparable systemic exposure in Korean de novo LDLT recipients. PR ‐T was efficacious; no new safety signals were detected.