Development and Clinical Validation of Model-Informed Precision Dosing for Everolimus in Liver Transplant Recipients

IF 4.9 Q1 CHEMISTRY, MEDICINAL ACS Pharmacology and Translational Science Pub Date : 2024-12-12 DOI:10.1021/acsptsci.4c0058110.1021/acsptsci.4c00581

Jeayoon Lee, In-Wha Kim, Suk Kyun Hong, Nayoung Han, Kyung-Suk Suh and Jung Mi Oh*,

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引用次数: 0

Abstract

Everolimus presents significant dosing challenges due to between- and within-patient pharmacokinetic variabilities. This study aimed to develop and validate a model-informed precision dosing strategy for everolimus in liver transplant recipients. The dosing strategy was initially developed using retrospective data, employing nonlinear mixed-effects modeling. The model included readily measurable covariates, body surface area, albumin, and tacrolimus trough concentration. The dosing strategy was subsequently validated in a prospective trial, recommending 1 to 1.75 mg dosages every 12 h, depending on covariates. Lower dosages were recommended for patients with lower body surface area and albumin with adjustments based on tacrolimus trough concentration. The estimated pharmacokinetic parameters (typical value ± standard error), apparent clearance (CL/F: 15.0 ± 0.5 L/h), and apparent volume of distribution (V_d/F: 862 ± 79.3 L) were refined using prospective clinical data from 20 patients, reducing interindividual variations. This research successfully developed and validated a population pharmacokinetic model for everolimus. The developed “dosE” web-based platform translates our pharmacokinetic model into a practical tool for healthcare providers, exemplifying the application of pharmaceutical research in clinical practice and potentially improving therapeutic outcomes in liver transplantation.

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来源期刊

ACS Pharmacology and Translational Science Medicine-Pharmacology (medical)

CiteScore

10.00

自引率

3.30%

发文量

133

期刊介绍： ACS Pharmacology & Translational Science publishes high quality, innovative, and impactful research across the broad spectrum of biological sciences, covering basic and molecular sciences through to translational preclinical studies. Clinical studies that address novel mechanisms of action, and methodological papers that provide innovation, and advance translation, will also be considered. We give priority to studies that fully integrate basic pharmacological and/or biochemical findings into physiological processes that have translational potential in a broad range of biomedical disciplines. Therefore, studies that employ a complementary blend of in vitro and in vivo systems are of particular interest to the journal. Nonetheless, all innovative and impactful research that has an articulated translational relevance will be considered. ACS Pharmacology & Translational Science does not publish research on biological extracts that have unknown concentration or unknown chemical composition. Authors are encouraged to use the pre-submission inquiry mechanism to ensure relevance and appropriateness of research.