Effect of cyproterone acetate and its metabolites on the adrenal function in man, rhesus monkey and rat.

The effect of oral administration of 17 alpha-acetoxy-6-chloro-1,2 alpha-methylene-4,6]pregnadiene-3,20-dione (cyproterone acetate, Androcur) on the adrenal function in male hypersexual subjects and in female rhesus monkey was investigated on the basis of cortisol and ACTH levels in serum or plasma and excretion of cortisol and 17-ketosteroids. In addition, cyproterone acetate and its main metabolite alcohol of the main metabolite were characterized for treatment of male hypersexual subjects and female rhesus monkeys did not reveal any signs of adrenal suppression. Cyproterone acetate and its metabolites gave on indication of any appreciable anti-inflammatory effect in the adjuvant edema test in rats. However, there was a general increase in the level of blood glucose and liver glycogen as well as a reduction in body weight and organ weight (spleen, thymus and adrenal) in rats, in which 15 beta-hydroxy cyproterone was slightly more active with the exception of adrenal weight tests. It can be concluded that adult man and rhesus monkey are much less sensitive, is so at all, to some corticosteroid-like activities of cyproterone acetate and its main metabolites than the rat.

Characterization of a new potent heparin. 1 communication: Determinations of anticoagulant activity of a high potency heparin preparation in vivo using dog as an experimental animal and in vitro using dog and human plasma.

The anticoagulant effect of a highly potent heparin preparation was compared with a commercially available heparin in vivo after i.v. application in beagle dogs. The anticoagulant activity was determined using thrombin time, activated partial thromboplastin time and whole blood clotting time 5, 10 and 30 min after application. The relative potency of the heparin preparation (Schering) was found to be 1.62 to 2.52 times higher than heparin used for comparison (150 USP units/mg). The anticoagulant properties of both preparations were also studied in vitro using heparin concentrations from 0.44 to 7.0 microgram/ml dog and human plasma. The relative potency in vitro experiments using dog or human plasma were 1.62 and 1.63, respectively, on the basis of activated partial thromboplastin time. It was further demonstrated that the anticoagulant effect as determined by activated partial thromboplastin time in vitro on human plasma was 2 to 2.4 times more pronounced in both heparin preparations when compared to the effect exerted on dog plasma.

Characterization of a new potent heparin. 2nd communication: Chemical analysis of the carbohydrate content and determination of the biological activity of a new potent heparin preparation in vitro, using protamine neutralization and amidolytic methods for factor Xa and thrombin.

A new potent heparin preparation was further characterized for carbohydrate content and for biological activities in vitro using the protamine neutralization test and amidolytic methods for factor Xa and thrombin. The chemical analysis of the heparin preparations showed similar amounts of glucosamine and glucuronic acid as known for other heparin preparations. In protamine neutralization test the new heparin was 1.32 times more active than commercial heparin. The amidolytic method using chromogenic substrates S-2222 for factor Xa and S-2238 for thrombin demonstrated that the new heparin was also at least two times more effective than commercial heparin in increasing the rate of inactivation of these serin proteases through antithrombin III.