Model-Informed Precision Dosing of Everolimus: External Validation in Adult Renal Transplant Recipients.
Autor: | Zwart TC; Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Albinusdreef 2, 2333ZA, Leiden, The Netherlands. t.c.zwart@lumc.nl., Moes DJAR; Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Albinusdreef 2, 2333ZA, Leiden, The Netherlands.; Leiden Network for Personalized Therapeutics, Leiden, The Netherlands., van der Boog PJM; Department of Internal Medicine (Nephrology), Leiden University Medical Center, Leiden, The Netherlands., van Erp NP; Department of Pharmacy, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands., de Fijter JW; Department of Internal Medicine (Nephrology), Leiden University Medical Center, Leiden, The Netherlands.; LUMC Transplant Center, Leiden University Medical Center, Leiden, The Netherlands., Guchelaar HJ; Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Albinusdreef 2, 2333ZA, Leiden, The Netherlands.; Leiden Network for Personalized Therapeutics, Leiden, The Netherlands., Keizer RJ; InsightRX, San Francisco, CA, USA., Ter Heine R; Department of Pharmacy, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands. |
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Jazyk: | angličtina |
Zdroj: | Clinical pharmacokinetics [Clin Pharmacokinet] 2021 Feb; Vol. 60 (2), pp. 191-203. |
DOI: | 10.1007/s40262-020-00925-8 |
Abstrakt: | Background and Objective: The immunosuppressant everolimus is increasingly applied in renal transplantation. Its extensive pharmacokinetic variability necessitates therapeutic drug monitoring, typically based on whole-blood trough concentrations (C Methods: The retrospective dataset included 4123 pharmacokinetic observations from routine clinical therapeutic drug monitoring in 173 renal transplant recipients. Model appropriateness was confirmed with a visual predictive check. A fit-for-purpose analysis was conducted to evaluate whether the model accurately and precisely predicted a future C Results: The model showed adequate accuracy and precision for C Conclusions: We demonstrated that our population pharmacokinetic model was able to accurately and precisely predict future everolimus exposure from prior pharmacokinetic measurements. In addition, we illustrated the potential added value of performing everolimus therapeutic drug monitoring with haematocrit-normalised whole-blood concentrations. Our results provide reassurance to implement this methodology in clinical practice for further evaluation. |
Databáze: | MEDLINE |
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