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The relationship between the plasma drug concentration and the antihypertensive effect of felodipine was analyzed by an ion-channel binding model which takes into consideration the slow association/dissociation process of a drug at the calcium channel. The in vitro dissociation constant (Kd) of felodipine to the calcium channel in the heart of rats was determined, and was compared to the in vivo dissociation constant (Kd,calc) estimated by the pharmacodynamic analysis of the concentration-effect data in Japanese essential hypertensive patients obtained from literature. The relative relationship between Kd and Kd,calc of felodipine was substantially identical with eight other calcium channel blocking agents reported previously. This results suggested the possibility that we can predict the pharmacodynamic behavior of newly developed calcium channel blocking agents from the in vitro Kd value and plasma concentration-time profile in human using the ion-channel binding model.

In Vitro-in Vivo Correlation of Pharmacodynamics of Felodipine in Essential Hypertensive Patients Based on an Ion-Channel Binding Model.