Importance of hematocrit for a tacrolimus target concentration strategy View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2014-01

AUTHORS

Elisabet Størset, Nick Holford, Karsten Midtvedt, Sara Bremer, Stein Bergan, Anders Åsberg

ABSTRACT

PURPOSE: To identify patient characteristics that influence tacrolimus individual dose requirement in kidney transplant recipients. METHODS: Data on forty-four 12-h pharmacokinetic profiles from 29 patients and trough concentrations in 44 patients measured during the first 70 days after transplantation (1,546 tacrolimus whole blood concentrations) were analyzed. Population pharmacokinetic modeling was performed using NONMEM 7.2®. RESULTS: Standardization of tacrolimus whole blood concentrations to a hematocrit value of 45 % improved the model fit significantly (p<0.001). Fat-free mass was the best body size metric to predict tacrolimus clearance and volume of distribution. Bioavailability was 49 % lower in expressers of cytochrome P450 3A5 (CYP3A5) than in CYP3A5 nonexpressers. Younger females (<40 years) showed a 35 % lower bioavailability than younger males. Bioavailability increased with age for both males and females towards a common value at age >55 years that was 47 % higher than the male value at age <40 years. Bioavailability was highest immediately after transplantation, decreasing steeply thereafter to reach its nadir at day 5, following which it increased during the next 55 days towards an asymptotic value that was 28 % higher than that on day 5. CONCLUSIONS: Hematocrit predicts variability in tacrolimus whole blood concentrations but is not expected to influence unbound (therapeutically active) concentrations. Fat-free mass, CYP3A5 genotype, sex, age and time after transplant influence the tacrolimus individual dose requirement. Because hematocrit is highly variable in kidney transplant patients and increases substantially after kidney transplantation, hematocrit is a key factor in the interpretation of tacrolimus whole blood concentrations. More... »

PAGES

65-77

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00228-013-1584-7

DOI

http://dx.doi.org/10.1007/s00228-013-1584-7

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1025204866

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/24071959


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