Pharmacokinetic and pharmacodynamic characteristics of ganirelix (Antagon/Orgalutran). Part I. Absolute bioavailability of 0.25 mg of ganirelix after a single subcutaneous injection in healthy female volunteers.
OBJECTIVE
To assess the absolute bioavailability of ganirelix (Antagon/Orgalutran; NV Organon, Oss, the Netherlands) after a single SC injection.


METHODS
Randomized, crossover, pharmacokinetic study.


METHODS
Phase I clinical research unit.


METHODS
Nineteen healthy female volunteers of reproductive age.


METHODS
Two separate injections of 0.25 mg of ganirelix were given, one subcutaneously and one intravenously, with a washout period of 1 week between injections. Blood samples were taken for assessment of serum ganirelix concentrations, and blood pressure, heart rate, and adverse events were monitored.


METHODS
Pharmacokinetic parameters.


RESULTS
Fifteen subjects were evaluated. The mean concentration-time profile after SC administration was comparable to that after IV administration. The mean (+/- SD) peak concentration and time of occurrence after SC administration were 14.8+/-3.2 ng/mL and 1.1+/-0.3 hours, respectively. The mean (+/- SD) half-lives after IV administration and SC administration were highly similar (12.7+/-3.7 hours and 12.8+/-4.3 hours, respectively). Mean (+/- SD) AUC0-infinity (area under the concentration-time curve) values of 105+/-11 ng/mL x hours and 96+/-12 ng/mL x hours were calculated for IV administration and SC administration, respectively, resulting in an absolute mean (+/- SD) bioavailability of 91.3%+/-6.7%. Both treatments were well tolerated.


CONCLUSIONS
Ganirelix is absorbed rapidly and extensively after SC administration, resulting in a high absolute bioavailability of >90%.
Oberyé
J J
JJ
Research and Development, NV Organon, Oss, The Netherlands. j.oberye@organon.oss.akzonobel.nl
Mannaerts
B M
BM
Kleijn
H J
HJ
Timmer
C J
CJ
D000328:Adult; D001682:Biological Availability; D018592:Cross-Over Studies; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000493:pharmacokinetics / Q000494:pharmacology; D006727:Hormone Antagonists / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D012016:Reference Values
D006727:Hormone Antagonists; D007987:Gonadotropin-Releasing Hormone; C061018:ganirelix