ETHYNODIOL DIACETATE METABOLITES IN HUMAN PLASMA

¹ Chemistry and Life Sciences Division, Research Triangle Institute, Research Triangle Park, North Carolina; Division of Biochemical Research, Searle Laboratories, Inc., Skokie, Illinois (A.K., R.E.R.); Department of Pharmacology, University of Arizona School of Medicine, Tucson, Arizona (R.C.B.)
² Chemistry and Life Sciences Division, Research Triangle Institute, Research Triangle Park, North Carolina; Division of Biochemical Research, Searle Laboratories, Inc., Skokie, Illinois (A.K., R.E.R.); and Department of Pharmacology, University of Arizona School of Medicine, Tucson, Arizona (R.C.B.)

Human plasma metabolites of ethynodiol diacetate (3,17-diacetoxy-l7-ethynyl-4-estrene) were identified by carrier addition analysis after oral administration of radiolabeled drug to a subject undergoing chronic treatment. Although a plasma half-life of 25 hours was observed for total radioactivity, the parent compound was not found 1 hour after administration. Carrier addition analysis showed the principal free plasma metabolite after 2 hours to be norethindrone (17-ethvnyl-17 -hydroxy-4-estren-3-one). Norethindrone was accompanied by its reduction products, 17-ethynyl-5-estrane-3, 17-diol and 17-ethynyl-5-estrane-3,17-diol. Two other isomeric reduction products of norethindrone, 17-ethynyl-5-estrane-3, 17-diol and 17-ethvnyl-5-estrane-3,17-diol, were also identified in the hydrolyzed plasma conjugate fraction, which made up the bulk of plasma radioactivity.