In ergot alkaloids a disproportion between the size of the peroral dose and the achieved area under the curve concentrations was described. This process can be explained by nonlinearity in the absorption, distribution or elimination of alkaloids. The aim of the present paper is to find whether elimination of tritiated DH-ergotoxine (3HDHE) in the liver is a linear, dose-independent process. Therefore on the model of the isolated rat liver disappearance of radioactivity in perfusate after the administration of two doses of 3HDHE, viz. 60 ng g-1 of the liver and 3030 ng g-1 of the liver, was investigated. The disappearance curves of radioactivity expressed as the percentage of the administered dose did not significantly differ between both groups. No significant changes between the groups were found either in the size of pharmacokinetic parameters, or in the portion of the administered radioactivity excreted in bile. Therefore the present authors think that disappearance of radioactivity in perfusate of the isolated liver after administration of 3HDHE is a linear process following first-order kinetics.

Dptm of Pharmacology Faculty of Medicine Hradec Králové