Pharmacokinetics and Toxicity of Tacrolimus Early After Heart and Lung Transplantation

M. A. Sikma, E. M. van Maarseveen, E. A. van de Graaf, J. H. Kirkels, M. C. Verhaar, D. W. Donker, J. Kesecioglu, J. Meulenbelt
  • American Journal of Transplantation, June 2015, Wiley
  • DOI: 10.1111/ajt.13309

pharmacokinetics of tacrolimus early after transplantation

What is it about?

Early after heart and lung transplantation, it is difficult to dose tacrolimus correctly, which leads to (nephro-)toxicity. The significantly altered pharmacokinetics in this critical phase are due to fluctuating drug absorption, changed protein metabolism, anemia and (multi-)organ failure. This review focuses on the tacrolimus pharmacokinetics, discusses relevant factors influencing the unbound tacrolimus concentrations and tacrolimus toxicity early after heart and lung transplantation.

Why is it important?

Morbidity and mortality after heart and lung transplantation are influenced by renal injury. Tacrolimus is the first choice immunosuppressive drug for heart and lung transplant recipients in the early phase post transplantation. Treatment with tacrolimus often deteriorates renal function. Consequently, improving tacrolimus management in heart and lung transplant recipients is of utmost importance.

Perspectives

Ms Maaike A. Sikma
University Medical Center Utrecht

It remains a challenge to dose tacrolimus well in the unstable phase after transplantation. This results from the complexity of all parameters influencing its pharmacokinetics. This minireview focuses on all the pharmacokinetic aspects of tacrolimus especially in the critically ill. Nowadays whole blood tacrolimus concentrations are used to guide dosing, though unbound tacrolimus plasma concentrations may be a more reasonable monitoring parameter for optimal tacrolimus dosing in the unstable patient.

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http://dx.doi.org/10.1111/ajt.13309

The following have contributed to this page: Professor Jan Meulenbelt, Ms Maaike A. Sikma, and Prof Marianne C Verhaar