Journal: Clinical and Translational Science

Article Title: Prediction of Safety Margin and Optimization of Dosing Protocol for a Novel Antibiotic using Quantitative Systems Pharmacology Modeling

doi: 10.1111/cts.12560

Figure Lengend Snippet: DILIsym simulations of prospective BAL30072 dosing protocols including 750 and 1,000 mg t.i.d. given over 4 hours in the SimPops version 3B‐1 (population sample) using the clinically optimized toxicity parameters. The alanine aminotransferase (ALT) dose stopping criterion was included in the simulations.

Article Snippet: Toxicity was simulated using SimPops version 3B‐1, a simulated population included in DILIsym version 3B that includes variability in parameters related to apoptosis, oxidative stress, and mitochondrial dysfunction.

Techniques:

Journal: Clinical and Translational Science

Article Title: Prediction of Safety Margin and Optimization of Dosing Protocol for a Novel Antibiotic using Quantitative Systems Pharmacology Modeling

doi: 10.1111/cts.12560

Figure Lengend Snippet: DILIsym simulations of BAL30072 in SimPops version 3B‐1 administered t.i.d. over 4 hours at escalating non‐weight‐adjusted doses to estimate the margin of safety for BAL30072 with respect to liver. BAL30072 doses were simulated at low, median, and high levels. The alanine aminotransferase (ALT) dose stopping criterion was included in the simulations. The purple brackets represent the dosing range that contains the lowest simulated dose at which DILIsym would predict a Hy's Law case. Outcomes related to hepatic effects, along with the peak plasma concentration (C max ) range of BAL30072, are shown.

Article Snippet: Toxicity was simulated using SimPops version 3B‐1, a simulated population included in DILIsym version 3B that includes variability in parameters related to apoptosis, oxidative stress, and mitochondrial dysfunction.

Techniques: Concentration Assay

Journal: Clinical and Translational Science

Article Title: Prediction of Safety Margin and Optimization of Dosing Protocol for a Novel Antibiotic using Quantitative Systems Pharmacology Modeling

doi: 10.1111/cts.12560

Figure Lengend Snippet: DILIsym simulations of BAL30072 in SimPops version 3B‐1 administered t.i.d. over 4 hours at escalating weight‐adjusted doses to estimate the margin of safety for BAL30072 with respect to liver. BAL30072 doses were simulated at low, median, and high levels. The alanine aminotransferase (ALT) dose stopping criterion was included in the simulations. The purple brackets represent the dosing range that contains the lowest simulated dose at which DILIsym would predict a Hy's Law case. Outcomes related to hepatic effects, along with the peak plasma concentration (C max ) range of BAL30072, are shown.

Article Snippet: Toxicity was simulated using SimPops version 3B‐1, a simulated population included in DILIsym version 3B that includes variability in parameters related to apoptosis, oxidative stress, and mitochondrial dysfunction.

Techniques: Concentration Assay