Pharmacokinetic and pharmacodynamic characteristics of ganirelix (Antagon/Orgalutran). Part II. Dose-proportionality and gonadotropin suppression after multiple doses of ganirelix in healthy female volunteers.
Fertil Steril
; 72(6): 1006-12, 1999 Dec.
Article
em En
| MEDLINE
| ID: mdl-10593372
ABSTRACT
OBJECTIVE:
To assess the dose-proportionality and pharmacodynamic properties of multiple doses of ganirelix (Antagon/Orgalutran; NV Organon, Oss, the Netherlands).DESIGN:
Randomized, parallel, pharmacokinetic, and pharmacodynamic study.SETTING:
Phase I clinical research unit. PATIENT(S) Three groups of 15 healthy female volunteers of reproductive age. INTERVENTION(S) Subcutaneous injections of 0.125 mg, 0.25 mg, or 0.50 mg of ganirelix were given once daily for 7 days. Blood samples were taken to assess serum ganirelix, LH, FSH, and E2 concentrations. MAIN OUTCOME MEASURE(S) Pharmacokinetic parameters and hormone suppression. RESULT(S) Steady-state levels were reached between days 2 and 3. Peak concentrations, which occurred approximately 1 hour after dosing, increased in a dose-proportional manner and averaged 5.2 ng/mL, 11.2 ng/mL, and 22.2 ng/mL for the 0.125-mg, 0.25-mg, and 0.50-mg doses, respectively. Corresponding mean values for the area under the curve over one dosing interval (24 hours) were 33 ng x h/mL, 77.1 ng x h/mL, and 137.8 ng x h/mL, respectively. After the last 0.25-mg dose of ganirelix, serum LH, FSH, and E2 concentrations were maximally decreased (by 74%, 32%, and 25% at 4 hours, 16 hours, and 16 hours after injection, respectively). Serum hormone levels returned to pretreatment values within 2 days after the last injection. CONCLUSION(S) The pharmacokinetics of ganirelix were dose-proportional within the dose range studied. Multiple injections resulted in immediate suppression of gonadotropins, which was rapidly reversed after treatment discontinuation.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Hormônio Liberador de Gonadotropina
/
Antagonistas de Hormônios
Tipo de estudo:
Clinical_trials
/
Prognostic_studies
Limite:
Adult
/
Female
/
Humans
Idioma:
En
Revista:
Fertil Steril
Ano de publicação:
1999
Tipo de documento:
Article
País de afiliação:
Holanda