Distribution of norethisterone and ethinylestradiol in the gravid rat and in the feto-placental unit of rhesus monkeys following intragastric administration of norethisterone acetate in combination with ethinylestradiol. I. Direct determinations.

The time course of the concentration of the 14C- and 3H-labelled substances and of unchanged norethisterone was determined in maternal plasma and selected tissues of the feto-placental unit after intragastric administration of a combination of 14C-norethisterone acetate (NET-Ac) and 3H-ethinylestradiol (EE2), respective commercial formulation: Ostro - Primolut , to pregnant rats. When given intragastrically in doses of 1 mg NET-Ac/kg and 0.002 mg EE2/kg both synthetic steroids were rapidly and completely absorbed. Highest concentrations of 14C-labelled substances were measured 0.5 h p. admin . in maternal and fetal tissues. Only approximately 1% of total radioactivity in maternal plasma (= 30 ng NET/ml) corresponded to unchanged norethisterone. Less than 1% of the dose administered passed the placental barrier. The maximum NET-levels in the fetuses amounted to 4 ng NET/g tissue. The highest levels of EE2-metabolites in the fetuses were found 2-5 h after administration with 34 pg EE2-equiv./g corresponding to only 0.15% of the dose administered in total fetuses. 14C- and 3H-radioactivity was eliminated from the fetuses with a similar or only a slightly lower rate than from the maternal organism. When administered intragastrically the twofold dose (2 mg NET-Ac/kg plus 0.004 mg EE2/kg) to pregnant rhesus monkeys maximum NET plasma levels of 40 ng/ml were observed after 2 h. Thereafter the NET plasma levels decreased with a half-life of 1.4 hours. The time course of NET concentrations in ovary and pituitary mirrored plasma levels whereas that in placenta and amniotic fluid paralleled plasma levels at a 30-50% and 3-15% niveau , respectively.(ABSTRACT TRUNCATED AT 250 WORDS)