Abstract A017: Computer simulation and quantification of the mass-action law-base pharmacodynamics parameters for anti-cancer and anti-viral therapeutics for single drugs and their combinations
Authors: Chou Ting-Chao David 
Published: December 2023

Abstract
The biophysical and biochemical fundamental principle of the mass-action law (MAL) was used as the solo model for broad-spectrum system analysis. These included linear and circular sequential analysis, pattern analysis, combinatorial analysis, and mathematical induction-deduction, for deriving unified general pharmacodynamics/biodynamics/combination index/and bioinformatics (PD/BD/CI/BI). The two unified general dose-effect dynamics theories are: “action” (Median-effect Eq., MEE) and “interaction” (Combination index Eq. CIE). All terms of MEE and CIE are dimensionless relativity ratios; thus, the applicability of the dynamics is regardless of unit (e.g., uM, IU, rad), mechanisms (e.g., sequential, ordered, random; competitive, non-competitive, uncompetitive), and physical states (e.g., chemicals, biologicals, radiation, photonic, and thermal effects), and their interactions. The unified “action” dynamics (MEE) is applicable for R&D for MAL identity’s basic-PD parameters: Dm, the median-effect dose, signifying potency; and m, the dynamic-order, signifying shapes of dose-effect curves (DEC), for single drugs or in combinations. The Dm and m values can be determined by computer simulation based on MEE and CIE algorithms computer software, which allows digital determination of synergism (CI&lt;1), additive effect (CI=1), and antagonism (CI&gt;1) by automated simulations, instantly, after Dose and Effect paired data entries. The MEE algorithm and plot (MEP) linearized DEC into straight lines. This linearization principle led to the minimum two data points theory (MTDPT), which adds “dose-zero” and “Dm)” two dose-data points to the PD algorithm by default, for dynamics simulations. The MTDPT is the theoretical basis for Econo-green, efficient, cost-effective biomedical research in vitro, animals, humans, environmental, agricultural, marine, and food sciences. This allows using small-size experimental studies, reducing cost, and increasing efficiency by computer simulation. This paper illustrates the examples (experimental or clinical trial protocol) of PD design, step-by-step, for dose-dependent PD computer analysis, for anti-cancer and anti-viral agents, e.g., fludelone +/- panaxytriol in vitro; microtubule-stabilization agent +/- T607 antineoplastic in colon carcinoma HCT116 tumor-bearing nude mice; as well as anti-HIV clinical trials [nucleoside reverse transcriptase inhibitor +/- Interferon], are used for detailed illustrations for study design, computerized data analysis, and automated print-out. Thus, the unified general MAL- PD/BD/CI/BI can be used in vitro, in animals, and in clinical trials, for digital informatics or ranking. It is worth noting that the Google Scholar and Web of Science bibliometrics (as of May 29, 2023), on the MAL-PD/CI original article (Chou TC & Talalay P, 1984), Review (Chou TC, 2006), and Perspectives (Chou TC, 2010) have received a total of 18,046 citations in over 1,500 journals. For relevant 2023 references, please visit https://doi.org/10.1016/j.jbc.2023.103419 and dx.doi.org/10.1124/jpet.122.185320.
Citation Format: Ting-Chao David Chou. Computer simulation and quantification of the mass-action law-base pharmacodynamics parameters for anti-cancer and anti-viral therapeutics for single drugs and their combinations [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr A017.