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

Journal: Pharmacology Research & Perspectives

Article Title: Prediction of clinical pharmacokinetics of AMG 181, a human anti- α 4 β 7 monoclonal antibody for treating inflammatory bowel diseases

doi: 10.1002/prp2.98

Figure Lengend Snippet: Schema of the two-compartment PK model with target-mediated drug disposition (TMDD) and quasi-equilibrium (QE) approximation.

Article Snippet: Individual PK data were simultaneously fit to a two-compartment PK model with target-mediated drug disposition (TMDD) (Mager and Jusko ) using quasi-steady-state (QSS) approximation (Gibiansky et al. ) or quasi-equilibrium (QE) approximation (Mager and Krzyzanski ).

Techniques:

Journal: Pharmacology Research & Perspectives

Article Title: Prediction of clinical pharmacokinetics of AMG 181, a human anti- α 4 β 7 monoclonal antibody for treating inflammatory bowel diseases

doi: 10.1002/prp2.98

Figure Lengend Snippet: Simultaneous fitting of the individual AMG 181 concentration–time data from all cynomolgus monkeys using the two-compartment TMDD QE PK model: (A) Single IV or SC dose and (B) 2-weekly, 13-weekly, or 24-weekly IV or SC doses. Symbols represent mean (±SD) observations. Solid lines represent the mean of model predicted individual concentration–time profiles in the respective cohort.

Article Snippet: Individual PK data were simultaneously fit to a two-compartment PK model with target-mediated drug disposition (TMDD) (Mager and Jusko ) using quasi-steady-state (QSS) approximation (Gibiansky et al. ) or quasi-equilibrium (QE) approximation (Mager and Krzyzanski ).

Techniques: Concentration Assay

Journal: Pharmacology Research & Perspectives

Article Title: Prediction of clinical pharmacokinetics of AMG 181, a human anti- α 4 β 7 monoclonal antibody for treating inflammatory bowel diseases

doi: 10.1002/prp2.98

Figure Lengend Snippet: Diagnostic plots for the two-compartment TMDD QE PK model: (A) Observed versus population predicted concentrations. (B) Observed vs. individual Bayesian predicted concentrations. (C) Conditional weighted residuals with interactions versus population predicted concentrations. (D) Conditional weighted residuals with interactions versus time post first dose. Symbols are observations and the blue lines are LOESS regression (local regression) lines. The black lines in (A) and (B) are lines of unity, while, in (C) and (D), lines of zero CWRESI.

Article Snippet: Individual PK data were simultaneously fit to a two-compartment PK model with target-mediated drug disposition (TMDD) (Mager and Jusko ) using quasi-steady-state (QSS) approximation (Gibiansky et al. ) or quasi-equilibrium (QE) approximation (Mager and Krzyzanski ).

Techniques: Diagnostic Assay

Journal: Pharmacology Research & Perspectives

Article Title: Prediction of clinical pharmacokinetics of AMG 181, a human anti- α 4 β 7 monoclonal antibody for treating inflammatory bowel diseases

doi: 10.1002/prp2.98

Figure Lengend Snippet: AMG 181 PK parameter estimates in cynomolgus monkeys through simultaneous fitting of the individual AMG 181 concentration- time data using the two-compartment pharmacokinetic target-mediated drug disposition (TMDD) model with quasi-equilibrium (QE) approximation

Article Snippet: Individual PK data were simultaneously fit to a two-compartment PK model with target-mediated drug disposition (TMDD) (Mager and Jusko ) using quasi-steady-state (QSS) approximation (Gibiansky et al. ) or quasi-equilibrium (QE) approximation (Mager and Krzyzanski ).

Techniques: Concentration Assay

Journal: Pharmacology Research & Perspectives

Article Title: Prediction of clinical pharmacokinetics of AMG 181, a human anti- α 4 β 7 monoclonal antibody for treating inflammatory bowel diseases

doi: 10.1002/prp2.98

Figure Lengend Snippet: Visual predictive checks for the two-compartment TMDD QE PK model (by cohort): median predictions (solid lines) with 80% confidence intervals (10th and 90th percentiles; dashed lines). Symbols represent observed individual AMG 181 concentrations.

Article Snippet: Individual PK data were simultaneously fit to a two-compartment PK model with target-mediated drug disposition (TMDD) (Mager and Jusko ) using quasi-steady-state (QSS) approximation (Gibiansky et al. ) or quasi-equilibrium (QE) approximation (Mager and Krzyzanski ).

Techniques:

Journal: Pharmacology Research & Perspectives

Article Title: Prediction of clinical pharmacokinetics of AMG 181, a human anti- α 4 β 7 monoclonal antibody for treating inflammatory bowel diseases

doi: 10.1002/prp2.98

Figure Lengend Snippet: The two-compartment TMDD QE PK model predicted typical AMG 181 PK profiles in humans: (A) Single SC or IV dose (lines) overlaid with the observed mean (SD) data (symbols). (B) Three-monthly SC doses. E max PD model predicted EC 50 , EC 75 , EC 90 , and EC 99 values are presented to illustrate duration of AMG 181 concentration coverage over α 4 β 7 receptor under each dosing regimen.

Article Snippet: Individual PK data were simultaneously fit to a two-compartment PK model with target-mediated drug disposition (TMDD) (Mager and Jusko ) using quasi-steady-state (QSS) approximation (Gibiansky et al. ) or quasi-equilibrium (QE) approximation (Mager and Krzyzanski ).

Techniques: Concentration Assay

Journal: Pharmacology Research & Perspectives

Article Title: Prediction of clinical pharmacokinetics of AMG 181, a human anti- α 4 β 7 monoclonal antibody for treating inflammatory bowel diseases

doi: 10.1002/prp2.98

Figure Lengend Snippet: Predicted AMG 181 pharmacokinetic exposure parameters in humans based on the two-compartment model with target-mediated drug disposition (TMDD) and quasi-equilibrium (QE) approximation

Article Snippet: Individual PK data were simultaneously fit to a two-compartment PK model with target-mediated drug disposition (TMDD) (Mager and Jusko ) using quasi-steady-state (QSS) approximation (Gibiansky et al. ) or quasi-equilibrium (QE) approximation (Mager and Krzyzanski ).

Techniques:

Journal: Pharmacology Research & Perspectives

Article Title: Prediction of clinical pharmacokinetics of AMG 181, a human anti- α 4 β 7 monoclonal antibody for treating inflammatory bowel diseases

doi: 10.1002/prp2.98

Figure Lengend Snippet: The mean (SD) observed AMG 181 C max (A) and AUC inf (B) data versus the values calculated using the two-compartment TMDD QE PK model predictions in humans after single SC or IV dose. The middle lines represent the lines of unity, while the upper and lower lines represent the lines of ±2-fold of unity.

Article Snippet: Individual PK data were simultaneously fit to a two-compartment PK model with target-mediated drug disposition (TMDD) (Mager and Jusko ) using quasi-steady-state (QSS) approximation (Gibiansky et al. ) or quasi-equilibrium (QE) approximation (Mager and Krzyzanski ).

Techniques: