PHARMACODYNAMICS AND PHARMACOKINETICS AFTER REPEATED SUBCUTANEOUS ADMINISTRATION OF 3 GONADOTROPIN PREPARATIONS

Recently, several new urinary gonadotrophin preparations have been dev eloped, containing less luteinizing hormone (LH) activity than human m enopausal gonadotrophin. Normegon is a gonadotrophin preparation with a follicle stimulating hormone (FSH)/LH ratio of 3:1; Follegon and Met rodin-HP are purified FSH preparations, The aim of the present randomi zed study was to compare pharmacodynamics, - kinetics and local tolera nce of these preparations after repeated s.c. administration. Thirty-s ix healthy female subjects were treated with Lyndiol contraceptive pil ls for 5 weeks to suppress endogenous gonadotrophin concentrations. Af ter 3 weeks of Lyndiol treatment, 150 IU of Normegon, Follegon or Metr odin HP were administered once daily, s.c. for 7 days. Blood samples w ere collected once daily during the fourth and fifth weeks of the stud y and assayed for FSH and oestradiol. After the last gonadotrophin inj ection, blood samples were collected more frequently to determine phar macokinetic parameters of FSH. During the fourth and fifth study weeks , daily ultrasound measurements of follicular growth were performed, E ndogenous FSH and LH values were extremely suppressed during Lyndiol t reatment. Serum FSH values showed similar patterns in the three groups . The maximum FSH concentration was reached 9-11 h post-injection, the terminal half-life was 43-47 h. The preparations were bioequivalent w ith respect to FSH immunoreactivity. The number of follicles tended to be larger after Normegon than after Follegon and Metrodin HP treatmen t, though this was not statistically significant. Serum oestradiol con centrations were significantly higher after Normegon treatment. In gen eral, s.c injections were well tolerated. In conclusion, the three pre parations were bioequivalent with respect to FSH immunoreactivity. Nev ertheless, the biological activity of Normegon tended to be higher tha n that of Follegon and Metrodin HP in Lyndiol-suppressed women.