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.


METHODS
Open, group-comparative, randomized, multiple-dose study.


METHODS
Phase I Clinical Research Unit.Volunteer(s): Forty-six healthy female volunteers.


METHODS
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.


METHODS
FSH pharmacokinetic parameters, number, and size of follicles.


RESULTS
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.


CONCLUSIONS
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.
Voortman
G
G
Research and Development, NV Organon, Oss, The Netherlands. g.voortman@organon.oss.akzonobel.nl
Mannaerts
B M
BM
Huisman
J A
JA
D000328:Adult; D004305:Dose-Response Relationship, Drug; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D043373:Follicle Stimulating Hormone, Human; D006801:Humans; D007273:Injections, Intramuscular; D007279:Injections, Subcutaneous; D006080:Ovarian Follicle / Q000033:anatomy & histology / Q000187:drug effects; D011994:Recombinant Proteins / Q000493:pharmacokinetics / Q000627:therapeutic use; D012016:Reference Values; D013810:Therapeutic Equivalency
D043373:Follicle Stimulating Hormone, Human; D011994:Recombinant Proteins; D005640:Follicle Stimulating Hormone