Weight-based tacrolimus trough concentrations post liver transplant

Intern Med J. 2019 Jan;49(1):79-83. doi: 10.1111/imj.14043.

Abstract

Background: Tacrolimus is one of the most widely used liver transplant medications. With the increasing number of obese patients requiring liver transplants, knowledge of the effect of body size affecting post-transplant outcomes, for example drug exposure is increasingly required.

Aims: (i) To investigate whether patient body size (i.e. total bodyweight) affects trough plasma concentrations of tacrolimus when a standard mg/kg dosing regimen is used; and (ii) to investigate whether obese patients have different numbers of plasma concentrations outside the therapeutic range compared to non-obese patients in the first months after liver transplant.

Methods: Using a transplant database, data tacrolimus concentrations were available for 69 patients. Tacrolimus was initially dosed at a standard 0.1 mg/kg/day after liver transplant, and adjusted to maintain a target trough concentration. Trough blood samples, phenotypic and outcome variables were analysed.

Results: Trough concentrations were similar between obese and non-obese patients (P > 0.05) at each sampling day. At day 7 post-transplant, 85.7% and 79.5% of the observed plasma concentrations were outside the recommended therapeutic range for obese and non-obese patients respectively, at day 30, 52.9% and 57.4%, and at 6 months, 18.7% and 27.5%.

Conclusion: In the first week post-transplant, tacrolimus trough concentrations after standard mg/kg dosing post liver transplant appear to be corrected by total bodyweight. Obese patients have a similar number of trough plasma concentrations outside the therapeutic range compared to non-obese patients.

Keywords: body size; liver transplant; pharmacokinetics; tacrolimus.

MeSH terms

  • Adult
  • Aged
  • Body Weight*
  • Female
  • Humans
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / blood
  • Immunosuppressive Agents / pharmacokinetics
  • Liver Transplantation*
  • Male
  • Middle Aged
  • Obesity / blood*
  • Retrospective Studies
  • Tacrolimus / administration & dosage
  • Tacrolimus / blood*
  • Tacrolimus / pharmacokinetics

Substances

  • Immunosuppressive Agents
  • Tacrolimus