two compartment pk model  (MathWorks Inc)

Journal: Clinical Pharmacology and Therapeutics

Article Title: Calibration and Validation of a Mechanistic COVID‐19 Model for Translational Quantitative Systems Pharmacology – A Proof‐of‐Concept Model Development for Remdesivir

doi: 10.1002/cpt.2686

Figure Lengend Snippet: Schematic diagram of the mechanistic in silico COVID‐19 model. The in silico model includes two main submodels: ( a ) COVID‐19 disease model and ( b ) pharmacological model. The disease model consists of three submodules: virus life cycle, immune response module in lung, and immune response module in the lymphatic compartment. The pharmacological model describes the pharmacokinetics processes that translate drug dose to clinical exposure and then links it to the disease model. In this figure, remdesivir is shown as an example, whose pharmacological model is linked to the disease model at the point of virus replication due to remdesivir's known effect of suppressing SARS‐CoV‐2 replication. ³⁸ Drugs with other mechanisms of action may have other connection points. For example, pharmacological models of inflammation suppressors (e.g., IL‐6 antibody) can be linked to the disease model at the point of IL‐6 production. Multiple pharmacological modules (submodels) could be added to simulate drug combinations. COVID‐19, coronavirus disease 2019; EC 50 , half‐maximal effective concentration; Epi, epithelial cell; IFNα, interferon alpha; IL‐6, interleukin 6; IgG, immunoglobulin G; IgM, immunoglobulin M; SARS‐CoV‐2, severe acute respiratory syndrome coronavirus 2. This figure is a high‐level summary of essential processes connected by sequential arrows, with solid lines ending in filled circles representing cell death induced by immune responses (for example cytotoxic T cells killing infected epithelial cells). More details about reaction interconnections, rates, parameters, and equations are provided in the Supplementary Document.

Article Snippet: Due to the complex PKs of remdesivir, the pharmacological model includes two sequential components ( Figure ): remdesivir compartmental PK model and remdesivir intracellular metabolism model. A two‐compartment PK model was used to convert remdesivir intravenous (i.v.) dose to plasma concentration.

Techniques: In Silico, Concentration Assay, Infection