生理的要因を介した薬物反応と薬物動態の速度論的解析

抄録

For the analysis of antipyretics, it was assumed that: (1) The rat body is divided into two compartments, core and skin. (2) Metabolic heat (M) is generated in the core compartment. (3) Heat loss by vaporization (V) is mainly respiratory effect and occurs in the core compartment. (4) At the skin compartment, heat is gained from the core compartment by conduction (K) and is transferred to the ambient air by radiation and convection. (5) Central nervous system commands the efferent signals for M, K and V to change their values according to the changes in afferent signals from core and skin temperature. (6) The effect of antipyretics acts as afferent signals to the controller. For loop diuretics, it was assumed that: (1) The diuretic rate can be correlated with the urinary excretion rate of the drug. (2) If there is no intervention of the body fluid regulation system, the relationship of the diuretic rate and the corresponding urinary excretion rate can be described by Hill equation. (3) Intensity of the body fluid regulation is also described by Hill equation, in which, the intensity is correlated with the cumulative amount of the drug excreted in urine. For neuromuscular blockade, assumptions were: (1) There exists an acetylcholine (ACh) compartment at a motor nerve terminal. (2) ACh in the compartment is eliminated by a first-order rate process. (3) All of the ACh in the compartment is released by one electrical stimulus. (4) The compartment is replenished by two kinds of ACh mobilization. One is a slow mobilization with a constant rate and the other is a momentary mobilization which takes place just after the release of ACh. (5) The released ACh is metabolized immediately after binding to receptors and causing twitch response.