Metabolism of a new synthetic progestagen, Org 2969, in female volunteers. The distribution and excretion of radioactivity after an oral dose of the labelled drug.

ABSTRACT

PIP: Org 2969, a newly synthesized progestin from the laboratory of Organon Int B.V., Oss, the Netherlands, was ingested by women volunteers in an oral, radioactive dose to learn more about the drug's metabolism in humans. 4 female volunteeers were studied. The study was conducted in 2 phases, the first had volunteers ingesting about .1 mCi (50 mcg) of tritiated Org 2969 along with 50 mg of ethinylestradiol (as a single dose), and the second phase was a 10-day treatment with the same (50 mcg) dose of Org 2969 without radiolabel followed by administration of tritiated Org 2969. In Phase 1, peak level of total radioactivity occurred within 2-3 hours; this peak represented 3.16-5.02% of the dose administered per liter of serum. The corresponding figures for Phase 2 were 1.5-3 hours and 4.54-5.13%. Phase 2 samples had increased levels of freely-extractable steroids compared with Phase 1, which explains the difference in measurements. Another aspect of the difference in metabolism of the 2 doses must result from a change in kinetics of the metabolism of Org 2969 by pretreatment with Org 2969 (Phase 2) or simultaneous administration with ethinylestradiol (Phase 1). 1 level was significantly different between Phase 1 and 2 and that was amount of drug excreted in feces. In Phase 1, mean recoveries of radioactivity in urine and feces were 83%/48.1%/34.9% (total/urine/feces) and for Phase 2 the same recoveries were 76.1%/45.2%/30.9%.