title: Termination of early pregnancy with ZK 98,734: pharmacokinetic behaviour and clinical effect.
abstract: The antiprogestin RU 486 (mifepristone) is highly effective in inducing early abortion in women only if the compound is combined with a prostaglandin analogue. A new related antiprogestin, ZK 98,734, has been reported in animal studies to be much more potent as an abortifacient than mifepristone, concomitant with less antiglucocorticoid activity. The aim of the present two-centre study was to explore the abortifacient efficacy and plasma concentrations of ZK 98,734 in women seeking abortion. A total of 96 pregnant women with amenorrhoea of < 49 days were treated with oral doses of 12.5, 25, 50 or 100 mg ZK 98,734 twice daily for 4 days. The overall rate of complete abortion and continuing live pregnancies was 68 and 20% respectively, i.e. results comparable with treatment with mifepristone alone. No dose-response relationship was noted. In patients with complete abortion, signs of luteal dysfunction in terms of oestradiol and progesterone production were evident on the fourth treatment day, in contrast to patients with failures. Increased amounts of cortisol and prolactin were found during treatment both in successfully treated patients and failures, whereas aldosterone values remained unaffected. The effect on cortisol may indicate some antiglucocorticoid activity in the human. The concentrations of ZK 98,734 in peripheral blood after 25, 50 and 100 mg twice daily for 4 days were similar. The values were slightly above 0.5 mumol/l on the second day of treatment. Maximal concentrations of 0.7 mumol/l were seen on treatment day 4. Plasma concentrations of ZK 98,734 did not differ in cases of complete abortion and failures.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Obstetrics and Gynaecology, Karolinska Hospital, Stockholm, Sweden.
authors.forename: M L
authors.initials: ML
authors.lastname: Swahn
authors.forename: L
authors.initials: L
authors.lastname: Kovács
authors.forename: S Z
authors.initials: SZ
authors.lastname: Cekan
authors.forename: A R
authors.initials: AR
authors.lastname: Aedo
authors.forename: P
authors.initials: P
authors.lastname: Westlund
mesh_terms: D000032:Abortion, Therapeutic / Q000379:methods*; D000293:Adolescent; D000328:Adult; D004963:Estrenes / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D006728:Hormones / Q000097:blood; D006801:Humans; D009325:Nausea / Q000139:chemically induced; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011372:Progestins / Q000037:antagonists & inhibitors*; D016896:Treatment Outcome; D014592:Uterine Hemorrhage / Q000139:chemically induced
chemical_list: D004963:Estrenes; D006728:Hormones; D011372:Progestins; C048260:lilopristone