Kinetics of drug activities as influenced by their physico-chemical properties: antibacterial effects of alkylating 2-furylethylenes.
A method is presented allowing for direct incorporation of the time of exposure into the relationship between biological and physico-chemical properties of drugs. The approach employs kinetics of the drug-receptor interaction based on mass action law, whereby biological response is considered as proportional to the receptor modification, and the time-dependent drug concentration in the vicinity of receptors is expressed by a disposition function. The function with variable physico-chemical properties and time relates the intracellular drug concentration to the dose. General description of individual steps in the development of a quantitative structure-time-activity relationship (QSTAR) is illustrated in detail using the data on antibacterial effects of alkylating 2-furylethylenes. It is shown that common approaches to description of quantitative structure-activity relationships (QSAR), working with a prefixed time of exposure, represent special cases of the method presented and can even be improved using its conclusions.
Department of Biochemical Technology, Slovak Polytechnic University, Bratislava, Czechoslovakia.
S
S
Baláz
E
E
Sturdík
M
M
Rosenberg
J
J
Augustín
B
B
Skára
D001419:Bacteria / Q000187:drug effects; D005030:Ethylenes / Q000494:pharmacology; D005663:Furans / Q000494:pharmacology; D007700:Kinetics; D008433:Mathematics; D008954:Models, Biological; D010599:Pharmacokinetics; D011955:Receptors, Drug / Q000378:metabolism
D005030:Ethylenes; D005663:Furans; D011955:Receptors, Drug