Once-daily tacrolimus extended-release formulation: 1-year post-conversion in stable pediatric liver transplant recipients

Am J Transplant. 2007 Jun;7(6):1609-15. doi: 10.1111/j.1600-6143.2007.01803.x.

Abstract

The pharmacokinetics, safety and tolerability of a once-daily formulation of tacrolimus (tacrolimus extended-release formulation; XL formerly referred to as MR or MR4) were assessed in 18 stable pediatric liver transplant recipients who were converted from the twice-a-day formulation of tacrolimus (TAC) to XL. Patients received their twice-a-day dose of TAC on study days 1 through 7. Beginning on the morning of study day 8, patients were converted to XL on a 1:1 (mg:mg) basis for their total daily dose, and were maintained on a once-daily AM dosing regimen using the same therapeutic monitoring and patient care techniques employed with TAC. Based on pharmacokinetic profiles obtained on study days 7 (TAC) and 14 (XL), steady state exposure (AUC(0-24)) was equivalent between XL and TAC; the mean XL/TAC ratio for lnAUC(0-24) was 100.9% (90% CI: 90.8%, 112.1%). AUC(0-24) and C(min) were strongly correlated at steady state (correlation coefficient: XL 0.90, TAC 0.94). During the first year post-conversion, there were no cases of acute rejection, discontinuation of XL, graft loss or death. The safety profile of XL was consistent with that known for TAC. These results support the safe and convenient conversion of pediatric liver transplant recipients from twice-a-day TAC to once-daily XL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Area Under Curve
  • Child
  • Child, Preschool
  • Delayed-Action Preparations
  • Drug Administration Schedule
  • Female
  • Follow-Up Studies
  • Humans
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / pharmacokinetics
  • Immunosuppressive Agents / therapeutic use
  • Liver Transplantation / immunology*
  • Male
  • Tacrolimus / administration & dosage
  • Tacrolimus / pharmacokinetics
  • Tacrolimus / therapeutic use*
  • Time Factors

Substances

  • Delayed-Action Preparations
  • Immunosuppressive Agents
  • Tacrolimus