Computerized quantification of drugs synergism in animal studies or in clinical trials using only ten data points

Ting Chao Chou, Theresa A. Shapiro, Jianing Fu, Joseph H. Chou, Gudrun S. Ulrich-Merzenich

Research output: Contribution to journalReview articlepeer-review

Abstract

The median-effect equation (MEE) derived from the mass-action law (MAL) is the unified theory of dose-effect pharmacodynamics (PD) and biodynamics (BD). MEE enables the linearization of a dose-effect curve into a straight linedefined by two data points. Thus any two data points can represent an entire dose-effect curve. For dose-effect curves using MAL, dose-zero can serve as 3rd point, and the universal reference point, the median-effect dose (Dm) serves as 4th point. This functionality has tremendous significance for in vivo studies. Fewer data points are required for a dose-effect curve, facilitating economical and ethically sustainable PD analyses. The extension of MEE from a single drug to multiple drugs establishes the general combination index equation (CIE), which quantitatively defines synergism (CI < 1), additive effect (CI = 1) and antagonism [CI > 1]. Although the CI method is often (>6000 citations) applied in in vitro studies, it is rarely used in animal studies or clinical trials. In vivo drug combination studies that use only single dose or statistical p value analyses do not allow quantitative synergy claims. This article presents two examples for drug combinations in vivo: (i) in animals (anticancer drug combination against human HCT-116 colon carcinoma xenografts in nude mice, Taxotere + T607) and (ii) in a clinical trial (anti-retroviral drug combinations against HIV/AIDS, AZT + INF). Only 36 patients respectively only 66 nude mice were required. Both examples require only ten data points (D1, D2 and [D1+D2], each with 3 doses plus one control) to quantitatively determine synergism or antagonism with the CompuSyn software.

Original languageEnglish (US)
Article number100049
JournalSynergy
Volume9
DOIs
StatePublished - Dec 2019

Keywords

  • Combination index
  • CompuSyn software
  • Drug combination in animals
  • Drug combination in clinical trials
  • Synergy computation
  • Synergy definition
  • Synergy quantitation

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Molecular Biology
  • Cell Biology
  • Pharmacology (medical)

Fingerprint

Dive into the research topics of 'Computerized quantification of drugs synergism in animal studies or in clinical trials using only ten data points'. Together they form a unique fingerprint.

Cite this