A pharmacokinetic/pharmacodynamic model of ACE inhibition of the renin-angiotensin system for normal and impaired renal function

• Published in: Computers & chemical engineering Vol. 104; pp. 311 - 322
• Main Authors: Ford Versypt, Ashlee N., Harrell, Grace K., McPeak, Alexandra N.
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 02.09.2017
• Subjects: Chronic kidney disease; Hypertension; Nonlinear dynamic modeling; Parameter estimation; Systems pharmacology; Hypertension; Nonlinear dynamic modeling; Parameter estimation; Chronic kidney disease; Systems pharmacology
• ISSN: 0098-1354; 1873-4375
• DOI: 10.1016/j.compchemeng.2017.03.027

[Display omitted] •A model is developed for inhibition of the renin-angiotensin reaction network.•The model is parameterized for two ACE inhibitor drugs benazepril and cilazapril.•Impaired renal function is considered explicitly to account for chronic kidney disease. Angiotensin II (Ang II) is a hormone that regulates blood pressure and is produced by the renin-angiotensin system (RAS). Angiotensin converting enzyme (ACE) inhibitor drugs inhibit the production of Ang II. ACE inhibitors are well-characterized for use in hypertension, but they are not as well understood for use in chronic kidney disease. Existing models for ACE inhibitors have only been applied to normal renal function. Here, published experimental data for two ACE inhibitors (benazepril and cilazapril) in patients with normal and impaired kidneys are used to construct a pharmacokinetic model of the fate of drug doses in the circulatory system. A pharmacodynamic model connecting drug concentration to the inhibition of the RAS and production of Ang II is proposed and parameterized for the two drugs in the cases of normal and impaired renal function. The model is packaged as a MATLAB app to facilitate reuse for research and educational purposes.