Article ; Online: Breakthrough: a first-in-class virtual simulator for dose optimization of ACE inhibitors in translational cardiovascular medicine.
2023 Volume 13, Issue 1, Page(s) 3300
Abstract: The renin-angiotensin-aldosterone-systems (RAAS) play a central role in the pathophysiology of congestive heart failure (CHF), justifying the use of angiotensin converting enzyme inhibitors (ACEi) in dogs and humans with cardiac diseases. Seminal studies ...
| Abstract | The renin-angiotensin-aldosterone-systems (RAAS) play a central role in the pathophysiology of congestive heart failure (CHF), justifying the use of angiotensin converting enzyme inhibitors (ACEi) in dogs and humans with cardiac diseases. Seminal studies in canine CHF had suggested that the pharmacological action of benazepril was relatively independent of doses greater than 0.25 mg/kg P.O, thereby providing a rationale for the European labeled dose of benazepril in dogs with CHF. However, most of these earlier studies relied on measures of ACE activity, a sub-optimal endpoint to characterize the effect of ACEi on the RAAS. The objectives of this study were (i) to expand on previous mathematical modeling efforts of the dose-exposure-response relationship of benazepril on biomarkers of the RAAS which are relevant to CHF pathophysiology and disease prognosis; and (ii) to develop a software implementation capable of simulating clinical trials in benazepril in dogs bedside dose optimization. Our results suggest that 0.5 mg/kg PO q12h of benazepril produces the most robust reduction in angiotensin II and upregulation of RAAS alternative pathway biomarkers. This model will eventually be expanded to include relevant clinical endpoints, which will be evaluated in an upcoming prospective trial in canine patients with CHF. |
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| MeSH term(s) | Humans ; Animals ; Dogs ; Angiotensin-Converting Enzyme Inhibitors/pharmacology ; Angiotensin-Converting Enzyme Inhibitors/therapeutic use ; Prospective Studies ; Aldosterone/metabolism ; Renin-Angiotensin System ; Heart Failure/drug therapy ; Cardiovascular Agents/pharmacology ; Biomarkers/metabolism |
| Chemical Substances | Angiotensin-Converting Enzyme Inhibitors ; Aldosterone (4964P6T9RB) ; Cardiovascular Agents ; Biomarkers |
| Language | English |
| Publishing date | 2023-02-26 |
| Publishing country | England |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 2615211-3 |
| ISSN | 2045-2322 ; 2045-2322 |
| ISSN (online) | 2045-2322 |
| ISSN | 2045-2322 |
| DOI | 10.1038/s41598-023-30453-x |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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