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.