Single-dose pharmacokinetics and pharmacodynamics of recombinant human follicle-stimulating hormone (Org 32489*) in gonadotropin-deficient volunteers.
OBJECTIVE
To assess safety, pharmacokinetic, and pharmacodynamic properties of recombinant human follicle-stimulating hormone (FSH; Org 32489, Organon International, Oss, The Netherlands) after a single intramuscular injection in the buttock.


METHODS
In a prospective study, safety variables, serum FSH, luteinizing hormone, inhibin, estradiol (females only), and testosterone (males only) were evaluated up to a maximum of 11 days after injection of 300 IU recombinant FSH.


METHODS
Four specialist Reproductive Endocrinology and Infertility units.


METHODS
Fifteen men and women exhibiting all pituitary gonadotropin deficiency.


RESULTS
A single bolus of 300 IU recombinant FSH was well tolerated, and no drug-related adverse effects were noted. Comparison of before and after treatment safety variables, including serum antirecombinant FSH antibodies, showed no changes of clinical relevance. Analysis of serum FSH levels revealed comparable elimination half-lives of 44 +/- 14 (mean +/- SD) and 32 +/- 12 hours in women and men volunteers, respectively. In contrast, peak FSH concentrations were significantly lower in women than in men volunteers (4.3 +/- 1.7 versus 7.4 +/- 2.8 IU/L), and the time required to reach peak levels of FSH was significantly longer in women than in men (27 +/- 5 versus 14 +/- 8 hours). The area under the serum level versus time curve tended to be smaller in women than in men volunteers (339 +/- 105 versus 452 +/- 183 IU/L x hours), but the difference did not reach statistical significance. Together these data suggest that recombinant FSH is absorbed from its intramuscular depot to a lower rate and extent in women than in men. In both sexes a relationship between serum FSH levels and body weight was apparent. During the experimental period, other hormones remained low at baseline levels or were only slightly increased.


CONCLUSIONS
Our findings indicate that recombinant FSH is well tolerated and that it is absorbed from its intramuscular depot to a higher rate and extent in men than in women. After intramuscular administration, its half-life is in good agreement with that previously reported for natural FSH.
Mannaerts
B
B
Medical R & D Unit, Organon International, Oss, The Netherlands.
Shoham
Z
Z
Schoot
D
D
Bouchard
P
P
Harlin
J
J
Fauser
B
B
Jacobs
H
H
Rombout
F
F
Coelingh Bennink
H
H
D000328:Adult; D001835:Body Weight; D005260:Female; D005640:Follicle Stimulating Hormone / Q000009:adverse effects / Q000097:blood* / Q000493:pharmacokinetics* / Q000494:pharmacology; D043373:Follicle Stimulating Hormone, Human; D012739:Gonadal Steroid Hormones / Q000097:blood; D006062:Gonadotropins / Q000172:deficiency*; D006801:Humans; D008297:Male; D011994:Recombinant Proteins
D043373:Follicle Stimulating Hormone, Human; D012739:Gonadal Steroid Hormones; D006062:Gonadotropins; D011994:Recombinant Proteins; D005640:Follicle Stimulating Hormone