Dose-effect curves and relative biophasic drug levels: Elucidation of these concepts and the illustration of their use for the determination of bioavailability,rate of absorption,and time course of pharmacological response

The theoretical basis for the development of dose-effect curves, linear dynamic models, and relative biophasic drug levels as derived from pharmacological response intensity is presented. The presentation is kept sufficiently rigorous to demonstrate the theoretical soundness of the concepts, yet each concept is clearly explained and related to physical experimental variables so as to be physically meaningful. The use of these concepts for the determination of bioavailability, rate of absorption, and time course of drug action is demonstrated.Notation A _i amplitude coefficients for impulse response equations - BDA biophasic drug availability - CA cumulative amount of drug absorbed - C _p concentration of drug in the plasma - D magnitude of impulse input - D relative biophasic drug level - f(I) relative biophasic drug level (7) - G(s) transfer function for system - I intensity of pharmacological response - m _i time constant for impulse response equation - n number of compartments in the system - PDA physiological drug availability - Q _B biophasic drug level - RBA relative biophasic drug availability - s Laplace transform variable - SDA systemic drug availability - STD. standard dose - t time, the independent variable - u(t) unit impulse input - V _D volume of distribution - U(s) Laplace transform of unit impulse input - _t a function of time, defined by equation 1