Clinical Pharmacokinetics and Impact of Hematocrit on Monitoring and Dosing of Tacrolimus Early After Heart and Lung Transplantation

Maaike A. Sikma, Claudine C. Hunault, Alwin D.R. Huitema, Dylan W. De Lange, Erik M. Van Maarseveen

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

12 Citaten (Scopus)

Samenvatting

The calcineurin inhibitor tacrolimus is an effective immunosuppressant and is extensively used in solid organ transplantation. In the first week after heart and lung transplantation, tacrolimus dosing is difficult due to considerable physiological changes because of clinical instability, and toxicity often occurs, even when tacrolimus concentrations are within the therapeutic range. The physiological and pharmacokinetic changes are outlined. Excessive variability in bioavailability may lead to higher interoccasion (dose-to-dose) variability than interindividual variability of pharmacokinetic parameters. Intravenous tacrolimus dosing may circumvent this high variability in bioavailability. Moreover, the interpretation of whole-blood concentrations is discussed. The unbound concentration is related to hematocrit, and changes in hematocrit may increase toxicity, even within the therapeutic range of whole-blood concentrations. Therefore, in clinically unstable patients with varying hematocrit, aiming at the lower therapeutic level is recommended and tacrolimus personalized dosing based on hematocrit-corrected whole-blood concentrations may be used to control the unbound tacrolimus plasma concentrations and subsequently reduce toxicity.

Originele taal-2Engels
Pagina's (van-tot)403-408
Aantal pagina's6
TijdschriftClinical Pharmacokinetics
Volume59
Nummer van het tijdschrift4
DOI's
StatusGepubliceerd - 1 apr. 2020
Extern gepubliceerdJa

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