Pharmacokinetics of the Progestin Dienogest (STS 557) in Rabbits^*)

Abstract

Disposition and excretion of the progestin Dienogest (17 alpha-cyanomethyl-17 beta-hydroxy-estra-4,9-dien-3-one, STS 557) were investigated in female rabbits. Following single and repeated administration of the tritium-labelled compound the plasma concentration courses of total radioactivity (Dienogest + metabolites) and of the parent drug alone were estimated and also the urinary and fecal excretion of total radioactivity. From these data basic pharmacokinetic parameters were calculated. Additionally, the enterohepatic recirculation of biliary excreted metabolites was studied using bile of donors for oral administration to recipients. Following oral administration the high bioavailability of Dienogest which was already found in other animal species and in man could also be confirmed with rabbits. The parameters of Dienogest disposition do not differ significantly from those of the progestin levonorgestrel. Thus, the different effects of the both progestins in the McPhail-Clauberg assay in the rabbit cannot be attributed to differences in pharmacokinetics.