NextDose: A web-based Bayesian dose forecasting tool

 

Tacrolimus

 

Tacrolimus is widely used as an immunosuppressant after organ transplanation. It is measured in whole blood with concentrations approximately 100 times those in plasma (Sikma, Van Maarseveen et al. 2020). It has been recommended that whole blood concentrations be interpreted by standardization to those expected with a hematocrit of 45% (Storset, Holford et al. 2014, Storset, Holford et al. 2014, Staatz, Størset et al. 2015).

 

Body size is best described using predicted fat free mass and theory based allometric scaling. Concomitant steroid dosing markedly decreases tacrolimus oral bioavailability (Storset, Holford et al. 2014, Staatz, Størset et al. 2015).

 

Target Concentration

The recommended whole blood concentration of tacrolimus is around 7 mcg/L at steady state with as 12 h dosing interval. When this is standardized to a hematocrit of 45% it is equivalent to around 10 mcg/L. Target concentration attainment is improved using Bayesian forecasting and hematocrit based interpretation of whole blood concentrations(Storset, Holford et al. 2014).

Copyright All rights reserved | Developed by Sam Holford & Nick Holford 2012-2021

 

Sikma, M. A., E. M. Van Maarseveen, C. C. Hunault, J. M. Moreno, E. A. Van de Graaf, J. H. Kirkels, M. C. Verhaar, J. C. Grutters, J. Kesecioglu, D. W. De Lange and A. D. R. Huitema (2020). "Unbound Plasma, Total Plasma, and Whole-Blood Tacrolimus Pharmacokinetics Early After Thoracic Organ Transplantation." Clinical Pharmacokinetics 59(6): 771-780.

Staatz, C. E., E. Størset, T. K. Bergmann, S. Hennig and N. Holford (2015). "Tacrolimus pharmacokinetics after kidney transplantation – Influence of changes in haematocrit and steroid dose." British Journal of Clinical Pharmacology: DOI: 10.1111/bcp.12729.

Storset, E., N. Holford, S. Hennig, T. K. Bergmann, S. Bergan, S. Bremer, A. Asberg, K. Midtvedt and C. E. Staatz (2014). "Improved prediction of tacrolimus concentrations early after kidney transplantation using theory-based pharmacokinetic modelling." Br J Clin Pharmacol 78(3): 509-523.

Storset, E., N. Holford, K. Midtvedt, S. Bremer, S. Bergan and A. Asberg (2014). "Importance of hematocrit for a tacrolimus target concentration strategy." Eur J Clin Pharmacol 70(1): 65-77.