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Comparison of mass‐action law algorithm‐based pharmacodynamics with the conventional pharmacokinetic studies
Author(s) -
Chou TingChao
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.665.2
Subject(s) - mass action law , law of mass action , pharmacodynamics , pharmacokinetics , adme , action (physics) , pharmacology , clinical pharmacology , confidence interval , medicine , mathematics , statistics , thermodynamics , physics , quantum mechanics
Pharmacodynamics (PD) of dose‐effect is governed by the physico‐chemical principle of the mass‐action law. Its systematically derived equations can be deduced to the general median‐effect equation for single entity, and the combination index equation for multiple entity interactions (Chou TC. Pharmacol. Rev. 58: 621–681, 2006, free web access). However, pharmacokinetic (PK) formula are obtained for conventional utilities, such as t 1/2 , C max , V dis , and clearance rate that are associated with “time”, but not efficacy nor toxicity. PK offers the proper use of drug, e.g., interval/frequency of doses, and precaution for renal or hepatic deficiencies. Contemporary R&D has emphasized PK and ADME, however, rigorous investigation on PD has been grossly neglected which is attributable to the high rate of new drug R&D failure. PD should be the primer. Unfortunately, PD is an underdeveloped area, e.g., bio‐researchers are still drawing the empirical curves to fit numerous data points rather than using a small number of data points to fit the mass‐action law. Furthermore, drug combinations are widely used in treating cancer and AIDS, however, most bio‐researchers are still confused by nearly 20 different definitions for synergy claims without knowing that the mass‐action law algorithm is the key (Chou, Pharmacol. Rev. 58: 621–681, 2006; Scientist 21: 15, 2007; Cancer Res. 70: 440–446, 2010). This confusion leads to inefficiency and waste in research. This author concludes that the mass‐action law PD algorithms and software provide efficient, quantitative econo‐green bio‐research as illustrated in Chou, Integr. Biol. 3: 548–559, 2011 and in Am. J. Cancer Res. 1(7): 925–954, 2011.