High Variability of Whole-Blood Tacrolimus Pharmacokinetics Early After Thoracic Organ Transplantation

Maaike A. Sikma, Claudine C. Hunault, Erik M. Van Maarseveen, Alwin D. R. Huitema, Ed A. Van de Graaf, Johannes H. Kirkels, Marianne C. Verhaar, Jan C. Grutters, Jozef Kesecioglu, Dylan W. De Lange
  • European Journal of Drug Metabolism and Pharmacokinetics, November 2019, Springer Science + Business Media
  • DOI: 10.1007/s13318-019-00591-7

Post-transplant tacrolimus pharmacokinetics

What is it about?

Tacrolimus is a calcineurin inhibitor immunosuppressant extensively used in heart and lung transplantation. In the first week after heart and lung transplantation patients often show clinical instability with physiological changes, such as gut dysmotility, renal dysfunction and liver dysfunction. These changes may have large impact on the pharmacokinetics of tacrolimus. In this study in 10 heart and 20 lung recipients pharmacokinetics were studied. A two compartment model with first and zero order absorption was developed. The dose-to-dose variability showed to be larger than the between-subject variability. The variability in bioavailability far exceeded variability in other pharmacokinetic parameters. Therefore, the authors suggest to administer tacrolimus intravenously.

Why is it important?

Tacrolimus toxicity is often observed early after thoracic organ transplantation, especially nephrotoxicity. Improving tacrolimus dosing is therefore of utmost importance.


Ms Maaike A. Sikma
University Medical Center Utrecht

Intravenous administration of tacrolimus may improve dosing and may decrease toxicity early after thoracic organ transplantation.

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The following have contributed to this page: Ms Maaike A. Sikma