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Population pharmacokinetics of everolimus in patients with seizures associated with focal cortical dysplasia

Authors
 Jinha Park  ;  Se Hee Kim  ;  Jongsung Hahn  ;  Hoon-Chul Kang  ;  Sang-Guk Lee  ;  Heung Dong Kim  ;  Min Jung Chang 
Citation
 FRONTIERS IN PHARMACOLOGY, Vol.14 : 1197549, 2023-11 
Journal Title
FRONTIERS IN PHARMACOLOGY
Issue Date
2023-11
Keywords
epilepsy ; everolimus ; focal cortical dysplasia ; non-linear mixed-effect modeling ; population pharmacokinetics
Abstract
Background: Everolimus is an inhibitor of mammalian target of rapamycin complex 1. As mutations in TSC1 and TSC2, which cause partial-onset seizures associated with TSC, were found in focal cortical dysplasia type Ⅱ (FCD Ⅱ) patients, a clinical trial has been performed to explore the efficacy and safety of everolimus in FCD patients. However, no dosage regimen was determined to treat FCD II. To recommend an optimal dose regimen for FCD patients, a population pharmacokinetic model of everolimus in FCD patients was developed. Methods: The data of everolimus were collected from September 2017 to May 2020 in a tertiary-level hospital in Korea. The model was developed using NONMEM® software version 7.4.1 (Icon Development Solutions, Ellicott City, MD, United States). Results: The population pharmacokinetics of everolimus was described as the one-compartment model with first-order absorption, with the effect of BSA on clearance. The final model was built as follows: TVCL = 12.5 + 9.71 × (BSA/1.5), TVV = 293, and TVKA = 0.585. As a result of simulation, a dose higher than 7 mg/m2 is needed in patients with BSA 0.5 m2, and a dose higher than 6 mg/m2 is needed in patients with BSA 0.7 m2. A dose of 4.5 mg/m2 is enough in the population with BSA higher than 1.5 m2 to meet the target trough range of 5–15 ng/mL. Conclusion: Based on the developed pharmacokinetics model, the optimal dose of everolimus in practice was recommended by considering the available strengths of Afinitor disperz®, 2 mg, 3 mg, and 5 mg. Copyright © 2023 Park, Kim, Hahn, Kang, Lee, Kim and Chang.
Files in This Item:
T202400484.pdf Download
DOI
10.3389/fphar.2023.1197549
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Laboratory Medicine (진단검사의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pediatrics (소아과학교실) > 1. Journal Papers
Yonsei Authors
Kang, Hoon Chul(강훈철) ORCID logo https://orcid.org/0000-0002-3659-8847
Kim, Se Hee(김세희) ORCID logo https://orcid.org/0000-0001-7773-1942
Kim, Heung Dong(김흥동) ORCID logo https://orcid.org/0000-0002-8031-7336
Lee, Sang-Guk(이상국) ORCID logo https://orcid.org/0000-0003-3862-3660
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/197922
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