A dose proportionality study of subcutaneously and intramuscularly administered recombinant human follicle-stimulating hormone (Follistim /Puregon ) in healthy female volunteers

• Published in: Fertility and sterility Vol. 73; no. 6; pp. 1187 - 1193
• Main Authors: Voortman, Gerrit, Mannaerts, Bernadette M.J.L, Huisman, Jan A.M
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.06.2000; Elsevier Science
• Subjects: Adult; Bioequivalence; Biological and medical sciences; dose proportionality; Dose-Response Relationship, Drug; Female; Follicle Stimulating Hormone - blood; Follicle Stimulating Hormone - pharmacokinetics; Follicle Stimulating Hormone - therapeutic use; Follicle Stimulating Hormone, Human; follicular growth; Follistim; Hormones. Endocrine system; Humans; Injections, Intramuscular; Injections, Subcutaneous; intramuscular; Medical sciences; Ovarian Follicle - anatomy & histology; Ovarian Follicle - drug effects; pharmacodynamics; pharmacokinetics; Pharmacology. Drug treatments; Puregon; recombinant FSH; Recombinant Proteins - pharmacokinetics; Recombinant Proteins - therapeutic use; Reference Values; subcutaneous; Therapeutic Equivalency; subcutaneous; Puregon; Bioequivalence; recombinant FSH; follicular growth; pharmacodynamics; Follistim; intramuscular; pharmacokinetics; dose proportionality; Human; Gonadotropin; Intramuscular administration; Biological activity; Multiple dose; Ripening; Ovary; Randomization; Adenohypophyseal hormone; Female genital system; Clinical trial; Female; Subcutaneous administration; Recombinant protein; Pharmacokinetics; Ovarian follicle; Follicle stimulating hormone
• ISSN: 0015-0282; 1556-5653
• DOI: 10.1016/S0015-0282(00)00542-2

Objective: To assess pharmacokinetics (PK) and pharmacodynamics (PD) of subcutaneous (s.c.) administration of recombinant FSH in comparison with the intramuscular (i.m.) route. Design: Open, group-comparative, randomized, multiple-dose study. Setting: Phase I Clinical Research Unit. Volunteer(s): Forty-six healthy female volunteers. Intervention(s): All volunteers were treated with Lyndiol contraceptive pills for 6 weeks to suppress pituitary function. After 3 weeks of Lyndiol, volunteers were randomized to 75 IU, 150 IU, or 225 IU s.c. or 150 IU i.m. of recombinant FSH, administered once daily for 7 days. Serum samples were collected to determine immunoreactive FSH, LH, and E 2 levels. Ultrasonography was performed for measurement of follicular growth. Main Outcome Measure(s): FSH pharmacokinetic parameters, number, and size of follicles. Result(s): The s.c. doses tested showed dose-proportional pharmacokinetics. Subcutaneous and i.m. administration of 150 IU of recombinant FSH were bioequivalent. For the 75-IU group almost no follicles ≥10 mm were found. The mean (±SD) number of follicles ≥8 mm on the day of maximum stimulation in the 150 IU and 225 IU s.c. and 150 IU i.m. groups were 14.0 ± 7.1, 14.3 ± 8.2, and 6.5 ± 4.7. Conclusion(s): Pharmacokinetics of recombinant FSH were dose proportional within the dose range studied (75–225 IU). Subcutaneous and i.m. administration of 150 IU was bioequivalent with respect to pharmacokinetics, but after s.c. administration the number of growing follicles and estradiol response were higher.