Disposition of ORF 9326, a novel contragestational steroid, in animals

The disposition of ORF 9326 [17BETA-acetoxy-2alpha-chloro-3(p-nitrophenoxy) imino-5-androstane], an O-aryl oxime of 2beta-chlorodihydrotestosterone acetate, was studied in rats, dogs, monkeys and rabbits. Intravenous administration of 3H-ORF 9326 dissolved in PEG-400 to rats, dogs and monkeys resulted in a rapid decline of radioactivity in blood followed by a terminal slope suggesting long retention of radioactivity. Apparent half lives of radioactivity in blood were calculated to be from 50--95 hours for the three species, which peak levels of radioactivity in whole blood occurring within 4--7 hours after administration of the compound. Tissue distribution studies in the rat and dog indicate that body fat is one of the major depot areas for the drug and/or its metabolites. The major route of excretion for ORF 9326 and/or its metabolites in dog and rat is biliary whereas in monkey and rabbit it appears to be renal. Greater than 90% of the radioactive compounds excreted in the urine of dogs and monkeys following intravenous administration of 3H-ORF 9326 appear to be in the form of conjugates.