INTENSITÄT UND DAUER DER WIRKUNG VON 6α-METHYLPREDNISOLON UND SEINEN ESTERN AN DER RATTE

Abstract

ABSTRACT The effects of 6α-methylprednisolone in the form of free alcohol, acetate and cyclopentylpropionate were studied in rats after a single subcutaneous injection of equimolar doses in oily solution. Onset and duration of action as well as maxima of effects were determined with various methods. Using the Porter-Silber-reaction for free methylprednisolone in plasma and the fluorescence reaction for corticosterone, both exogenous and endogenous corticosteroids were measured in the same plasma sample. The liver glycogen deposition test in adrenalectomized rats was used as a parameter of action on carbohydrate metabolism. The granuloma pouch assay was modified by injecting the corticosteroid to be tested one, two, three or four weeks before the injection of the croton oil. The increase in tensile strength of connective tissue, e. g. the distal epiphyseal plate of the femur of rats and the rat's tail tendon, induced by corticosteroids was also used to investigate intensity and duration of action. Of the various measurements of duration of action, the tensile strength procedures had the greatest accuracy. The highest plasma levels of free methylprednisolone were achieved after the injection of the free alcohol. The degree of suppression of the endogenous corticosterone was almost the same after the injection of the various steroid preparations. However, the maximal effects in the liver glycogen assay, the granuloma pouch test and the tensile strength of the femur and the rat's tail tendon were achieved by the acetate and/or the cyclopentylpropionate. The effects on metabolism and on connective tissue were always delayed in comparison with the steroid plasma levels. As could be expected the duration of the effects was found to be in the following order: short: free alcohol, intermediate: acetate, prolonged (up to three weeks): cyclopentylpropionate. In Fortsetzung früherer Untersuchungen (Vogel 1963 a, b) soll die vorliegende Arbeit folgenden Fragestellungen dienen: Welche Methoden sind geeignet, sowohl die Wirkungsintensität als auch die Wirkungsdauer verschiedener Ester und Zubereitungen von Glucocorticoiden im Tierexperiment zu erfassen? Wie lange kann man den Effekt eines Depotpräparates verfolgen? Welche Beziehungen bestehen zwischen dem Blutspiegel des zugeführten Corticosteroids und den Stoffwechselveränderungen bzw. den Effekten auf das Bindegewebe?