دورية أكاديمية
CSL112 (Apolipoprotein A-I [Human]) Strongly Enhances Plasma Apoa-I and Cholesterol Efflux Capacity in Post-Acute Myocardial Infarction Patients: A PK/PD Substudy of the AEGIS-I Trial
| العنوان: | CSL112 (Apolipoprotein A-I [Human]) Strongly Enhances Plasma Apoa-I and Cholesterol Efflux Capacity in Post-Acute Myocardial Infarction Patients: A PK/PD Substudy of the AEGIS-I Trial |
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| المؤلفون: | C. Michael Gibson MS, MD, Syed Hassan A. Kazmi MD, Serge Korjian MD, Gerald Chi MD, Adam T. Phillips MD, Sahar Memar Montazerin MD, Danielle Duffy MD, Bo Zheng PhD, Mark Heise PhD, Charles Liss MS, Lawrence I. Deckelbaum MD, Samuel D. Wright PhD, Andreas Gille MD, PhD |
| المصدر: | Journal of Cardiovascular Pharmacology and Therapeutics, Vol 27 (2022) |
| بيانات النشر: | SAGE Publishing, 2022. |
| سنة النشر: | 2022 |
| المجموعة: | LCC:Diseases of the circulatory (Cardiovascular) system LCC:Therapeutics. Pharmacology |
| مصطلحات موضوعية: | Diseases of the circulatory (Cardiovascular) system, RC666-701, Therapeutics. Pharmacology, RM1-950 |
| الوصف: | Introduction: Cholesterol efflux capacity (CEC) is impaired following acute myocardial infarction (AMI). CSL112 is an intravenous preparation of human plasma-derived apoA-I formulated with phosphatidylcholine (PC). CSL112 is intended to improve CEC and thereby prevent early recurrent cardiovascular events following AMI. AEGIS-I (ApoA-I Event Reducing in Ischemic Syndromes I) was a multicenter, randomized, double-blind, placebo-controlled, dose-ranging phase 2b study, designed to evaluate the hepatic and renal safety of CSL112. Here, we report an analysis of a pharmacokinetic (PK) and pharmacodynamic (PD) substudy of AEGIS-I. Methods: AMI patients were stratified by renal function and randomized 3:3:2 to 4, weekly, 2-hour infusions of low- and high-dose (2 g and 6 g) CSL112, or placebo. PK/PD assessments included plasma concentrations of apoA-I and PC, and measures of total and ABCA1-dependent CEC, as well as lipids/lipoproteins including high density lipoprotein cholesterol (HDL-C), non-HDL-C, low density lipoprotein cholesterol (LDL-C), ApoB, and triglycerides. Inflammatory and cardio-metabolic biomarkers were also evaluated. Results: The substudy included 63 subjects from AEGIS-I. CSL112 infusions resulted in rapid, dose-dependent increases in baseline corrected apoA-I and PC, which peaked at the end of the infusion (T max ≈ 2 hours). Similarly, there was a dose-dependent elevation in both total CEC and ABCA1-mediated CEC. Mild renal impairment did not affect the PK or PD of CSL112. CSL112 administration was also associated with an increase in plasma levels of HDL-C but not non-HDL-C, LDL-C, apoB, or triglycerides. No dose-effects on inflammatory or cardio-metabolic biomarkers were observed. Conclusion: Among patients with AMI, impaired CEC was rapidly elevated by CSL112 infusions in a dose-dependent fashion, along with an increase in apoA-I plasma concentrations. Findings from the current sub-study of the AEGIS-I support a potential atheroprotective benefit of CSL112 for AMI patients. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1940-4034 10742484 |
| Relation: | https://doaj.org/toc/1940-4034 |
| DOI: | 10.1177/10742484221121507 |
| URL الوصول: | https://doaj.org/article/43aa47289dd347168bc134341711e1bc |
| رقم الأكسشن: | edsdoj.43aa47289dd347168bc134341711e1bc |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 19404034 10742484 |
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| DOI: | 10.1177/10742484221121507 |