Evaluation of Published Population Pharmacokinetic Models to Inform Tacrolimus Therapy in Adult Lung Transplant Recipients.

Autor:	Kirubakaran R; School of Clinical Medicine, St. Vincent's Healthcare Clinical Campus, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia.; Department of Clinical Pharmacology and Toxicology, St. Vincent's Hospital, Sydney, NSW, Australia.; Department of Pharmacy, Ministry of Health, Putrajaya, Malaysia.; School of Pharmacy, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia., Singh RM; School of Clinical Medicine, St. Vincent's Healthcare Clinical Campus, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia.; Department of Clinical Pharmacology and Toxicology, St. Vincent's Hospital, Sydney, NSW, Australia., Carland JE; School of Clinical Medicine, St. Vincent's Healthcare Clinical Campus, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia.; Department of Clinical Pharmacology and Toxicology, St. Vincent's Hospital, Sydney, NSW, Australia., Day RO; School of Clinical Medicine, St. Vincent's Healthcare Clinical Campus, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia.; Department of Clinical Pharmacology and Toxicology, St. Vincent's Hospital, Sydney, NSW, Australia., Stocker SL; School of Clinical Medicine, St. Vincent's Healthcare Clinical Campus, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia.; Department of Clinical Pharmacology and Toxicology, St. Vincent's Hospital, Sydney, NSW, Australia.; School of Pharmacy, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia.; Sydney Institute for Infectious Diseases, University of Sydney, Sydney, NSW, Australia ; and.; Sydney Musculoskeletal Health, University of Sydney, Sydney, NSW, Australia .
Jazyk:	angličtina
Zdroj:	Therapeutic drug monitoring [Ther Drug Monit] 2024 Aug 01; Vol. 46 (4), pp. 434-445. Date of Electronic Publication: 2024 May 09.
DOI:	10.1097/FTD.0000000000001210
Abstrakt:	Background: The applicability of currently available tacrolimus population pharmacokinetic models in guiding dosing for lung transplant recipients is unclear. In this study, the predictive performance of relevant tacrolimus population pharmacokinetic models was evaluated for adult lung transplant recipients. Methods: Data from 43 lung transplant recipients (1021 tacrolimus concentrations) administered an immediate-release oral formulation of tacrolimus were used to evaluate the predictive performance of 17 published population pharmacokinetic models for tacrolimus. Data were collected from immediately after transplantation up to 90 days after transplantation. Model performance was evaluated using (1) prediction-based assessments (bias and imprecision) of individual predicted tacrolimus concentrations at the fourth dosing based on 1 to 3 previous dosings and (2) simulation-based assessment (prediction-corrected visual predictive check; pcVPC). Both assessments were stratified based on concomitant azole antifungal use. Model performance was clinically acceptable if the bias was within ±20%, imprecision was ≤20%, and the 95% confidence interval of bias crossed zero. Results: In the presence of concomitant antifungal therapy, no model showed acceptable performance in predicting tacrolimus concentrations at the fourth dosing (n = 33), and pcVPC plots displayed poor model fit to the data set. However, this fit slightly improved in the absence of azole antifungal use, where 4 models showed acceptable performance in predicting tacrolimus concentrations at the fourth dosing (n = 33). Conclusions: Although none of the evaluated models were appropriate in guiding tacrolimus dosing in lung transplant recipients receiving concomitant azole antifungal therapy, 4 of these models displayed potential applicability in guiding dosing in recipients not receiving concomitant azole antifungal therapy. However, further model refinement is required before the widespread implementation of such models in clinical practice. Competing Interests: R. M. Singh, R. Kirubakaran, R. O. Day, J. E. Carland, and S. L. Stocker have no conflicts of interest to declare that are relevant to the content of this article. (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
Databáze:	MEDLINE
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