A Dose Proportionality Study of Subcutaneously and Intramuscularly Administered Recombinant Human Follicle-stimulating Hormone (Follistim*/Puregon) in Healthy Female Volunteers

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.