Pharmacokinetics and pharmacodynamics of single-chain recombinant human follicle-stimulating hormone containing the human chorionic gonadotropin carboxyterminal peptide in the rhesus monkey.
OBJECTIVE
To compare the pharmacokinetics of a long-acting FSH analog containing the hCG-beta carboxyterminal peptide (recombinant hFSH-CTP) with native recombinant hFSH and describe the pharmacodynamics of recombinant hFSH-CTP after SC injection in female rhesus monkeys.


METHODS
Rhesus monkey study.


METHODS
Academic research environment.


METHODS
Ten female rhesus monkeys.


METHODS
Recombinant hFSH and recombinant hFSH-CTP were administered via a single SC or IV dose to rhesus monkeys, and serial phlebotomy was performed (n = 2 and n = 4 for SC recombinant hFSH and recombinant hFSH-CTP, respectively; for IV dosing, n = 1 in each group). An additional two monkeys were pretreated with SC ganirelix and received SC recombinant hFSH-CTP after confirmation of pituitary suppression.


METHODS
Plasma disappearance rate of recombinant hFSH and recombinant hFSH-CTP and serum estradiol levels.


RESULTS
The elimination half-life of recombinant hFSH-CTP was twofold and fourfold longer than that for recombinant hFSH after SC and IV dosing, respectively. The absorption half-life was approximately threefold longer for recombinant hFSH-CTP than for recombinant hFSH after SC administration. Recombinant hFSH-CTP stimulates estradiol secretion for 5-7 days after an isolated SC dose.


CONCLUSIONS
Addition of the hCG-beta carboxyterminal peptide to hFSH-beta results in an FSH analog with longer absorption and elimination half-lives compared with native hormone. This analog is capable of prolonged ovarian stimulation in rhesus monkeys after an isolated SC injection.
Klein
Jeffrey
J
Department of Obstetrics and Gynecology, Columbia University, College of Physicians and Surgeons, New York 10032, USA.
Lobel
Leslie
L
Pollak
Susan
S
Ferin
Michel
M
Xiao
Ennian
E
Sauer
Mark
M
Lustbader
Joyce W
JW
D000042:Absorption; D000818:Animals; D001769:Blood / Q000378:metabolism; D004958:Estradiol / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D043373:Follicle Stimulating Hormone, Human; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008253:Macaca mulatta; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology
D043373:Follicle Stimulating Hormone, Human; D011994:Recombinant Proteins; C437186:follicle stimulating hormone, human, with HCG C-terminal peptide; D004958:Estradiol; D005640:Follicle Stimulating Hormone