Comparison of different methods to assess tacrolimus concentration intra-patient variability as potential marker of medication non-adherence
JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)
ID
4656243
Author(s)
Kostalova, Barbora; Mala-Ladova, Katerina; Sulkova, Sylvie Dusilova; Denhaerynck, Kris; De Geest, Sabina; Maly, Josef
Author(s) at UniBasel
Denhaerynck, Kris De Geest, Sabina M.
Year
2022
Title
Comparison of different methods to assess tacrolimus concentration intra-patient variability as potential marker of medication non-adherence
Journal
Frontiers in Pharmacology
Volume
13
Pages / Article-Number
973564
Keywords
immunosuppression; intra-patient variability; kidney transplantation; medication adherence; tacrolimus; tacrolimus immunosuppression
Abstract
Background and objective:; Non-adherence to tacrolimus commonly manifests as low drug concentrations and/or high intra-patient variability (IPV) of concentrations across multiple measurements. We aimed to compare several methods of tacrolimus IPV calculation and evaluate how well each reflects blood concentration variation due to medication non-adherence in kidney transplant recipients.; Methods:; This Czech single-center retrospective longitudinal study was conducted in 2019. All outpatients ≥18 years of age, ≥3 months post-transplant, and on tacrolimus-based regimens were approached. After collecting seven consecutive tacrolimus concentrations we asked participating patients to self-report adherence to immunosuppressants (BAASIS; ©; scale). The IPV of tacrolimus was calculated as the medication level variability index (MLVI), the coefficient of variation (CV), the time-weighted CV, and; via; nonlinearly modeled dose-corrected trough levels. These patient-level variables were analyzed using regression analysis. Detected nonlinearities in the dose-response curve were controlled for by adding tacrolimus dosing and its higher-order terms as covariates, along with self-reported medication adherence levels.; Results:; Of 243 patients using tacrolimus, 42% (; n; = 102) reported medication non-adherence. Non-adherence was associated with higher CVs, higher time-weighted CVs, and lower dose-corrected nonlinearly modeled trough levels; however, it was not associated with MLVIs. All of the significant operationalizations suggested a weak association that was similar across the applied methods.; Discussion and conclusion:; Implementation non-adherence was reflected by higher CV or time-weighted CV and by lower blood concentrations of tacrolimus. As an additional tool for identifying patients at risk for non-adherence, simple IPV calculations incorporated into medical records should be considered in everyday clinical practice.
Publisher
Frontiers Media
ISSN/ISBN
1663-9812
edoc-URL
https://edoc.unibas.ch/91741/
Full Text on edoc
Available
Digital Object Identifier DOI
10.3389/fphar.2022.973564
PubMed ID
http://www.ncbi.nlm.nih.gov/pubmed/36313323
ISI-Number
WOS:000877281400001
Document type (ISI)
Journal Article
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