Conversion from twice-daily tacrolimus capsules to once-daily extended-release tacrolimus (LCPT): A phase 2 trial of stable renal transplant recipients

A. Osama Gaber, Rita R. Alloway, Kenneth Bodziak, Bruce Kaplan, Suphamai Bunnapradist

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

BACKGROUND: LCP-Tacro is an extended-release formulation of tacrolimus designed for once-daily dosing. Phase 1 studies demonstrated greater bioavailability to twice-daily tacrolimus capsules and no new safety concerns. METHODS: In this phase 2 study, adult stable kidney transplant patients on tacrolimus capsules (Prograf) twice-daily were converted to tacrolimus tablets (LCP-Tacro) once-daily; patients continued on LCP-Tacro once-daily for days 8 to 21; trough levels were to be maintained between 5 and 15 ng/mL; 24-hr pharmacokinetic assessments were done on days 7 (baseline pre-switch), 14, and 21. RESULTS: Forty-seven patients completed LCP-Tacro dosing per protocol. The mean conversion ratio was 0.71. Pharmacokinetic data demonstrated consistent exposure (AUC) at the lower conversion dose. Cmax (P=0.0001), Cmax/Cmin ratio (P<0.001), percent fluctuation (P<0.0001), and swing (P=0.0004) were significantly lower and Tmax significantly (P<0.001) longer for LCP-Tacro versus Prograf. AUC24 and Cmin correlation coefficients after 7 and 14 days of therapy were 0.86 or more, demonstrating a robust correlation between LCP-Tacro tacrolimus exposure and trough levels. There were three serious adverse events; none were related to study drug and all were resolved. CONCLUSIONS: Stable kidney transplant patients can be safely converted from Prograf twice-daily to LCP-Tacro. The greater bioavailability of LCP-Tacro allows for once-daily dosing and similar (AUC) exposure at a dose approximately 30% less than the total daily dose of Prograf. LCP-Tacro displays flatter kinetics characterized by significantly lower peak-trough fluctuations.

Original languageEnglish (US)
Pages (from-to)191-197
Number of pages7
JournalTransplantation
Volume96
Issue number2
DOIs
StatePublished - Jul 27 2013

Keywords

  • Flatter kinetics
  • Kidney transplantation
  • LCP-Tacro
  • MeltDose
  • PK
  • Sustained-release preparations
  • Tacrolimus

ASJC Scopus subject areas

  • Transplantation

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