Determination of rate constants of drug elimination from the receptor compartment by an infusion method: Neurohypophysial hormones and their structural analogues

Abstract

An infusion method for determing the rate constant of drug elimination from the receptor compartment has been developed and compared with methods using single doses. For the antidiuretic effects of the neurohypophysial hormones and their structural analogues it gives results with a lower scatter. The method has been applied to analogues of the hormonogen type where the older methods are not very reliable because of the complex kinetics of activation and inactivation involved. The rate constants of drug elimination for antidiuretic, vasopressor and uterotonic effects of oxytocin and of lysine and arginine vasopressin have been determined together with the standard deviations (± 5% for the antidiuretic, ± 15% to ± 20% for the uterotonic and vasopressor response). The highest elimination constants were found for the pressor response; they approach the constants for elimination of the hormones from the plasma.