Conversion of twice-daily tacrolimus to once-daily tacrolimus formulation in stable pediatric kidney transplant recipients: pharmacokinetics and efficacy

Am J Transplant. 2013 Aug;13(8):2191-7. doi: 10.1111/ajt.12274. Epub 2013 Jun 4.

Abstract

The pharmacokinetics, efficacy and safety of once-daily tacrolimus formulation (Tac-OD) were assessed in 34 stable pediatric kidney transplant recipients. Enrolled patients received their dose of twice-daily tacrolimus formulation (Tac-BID) on study Days 0 through 7. On the morning of study Day 8, the total daily doses for patients were converted to Tac-OD on a 1:1 basis and maintained on a once-daily morning dosing regimen. Tacrolimus pharmacokinetic profiles were obtained on study Days 7, 14 and 28 (after dose adjustment). Although the mean C0 concentrations (4.10 ± 1.16-3.53 ± 1.10 ng/mL, p = 0.004), and AUC0-24 (151.8 ± 41.6-129.8 ± 39.3 ng h/mL, p < 0.001) were decreased significantly after a 1:1 based conversion, there was high interindividual variability. The dose of Tac-OD was decreased in 26.5% and increased in 44.1% of patients. The resultant tacrolimus dose and pharmacokinetic profiles on study Day 28 were comparable to those on Day 7. There were no serious adverse events. In conclusion, Tac-BID can be safely converted to Tac-OD in stable pediatric kidney transplant patients with the heightened therapeutic drug monitoring. Effects of drug conversion on the cardiovascular risk factors, neurological side effects and adherence should be further evaluated.

Keywords: Conversion; pediatric kidney transplantation; pharmacokinetics; tacrolimus.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Area Under Curve
  • Child
  • Child, Preschool
  • Drug Administration Schedule
  • Drug Monitoring*
  • Female
  • Follow-Up Studies
  • Humans
  • Immunosuppressive Agents / pharmacokinetics*
  • Immunosuppressive Agents / therapeutic use
  • Kidney Diseases / surgery*
  • Kidney Transplantation*
  • Male
  • Medication Adherence
  • Prognosis
  • Prospective Studies
  • Tacrolimus / pharmacokinetics*
  • Tacrolimus / therapeutic use
  • Tissue Distribution

Substances

  • Immunosuppressive Agents
  • Tacrolimus