Introduction
Ganirelix, a synthetic decapeptide compound, is a gonadotrophin-releasing hormone (GnRH) antagonist preparation developed for the prevention of premature luteinizing hormone (LH) surges in women undergoing ovarian stimulation. Amino acid substitutions at positions 1, 2, 3, 6, 8 and 10 of the sequence of native GnRH resulted in a potent and safe antagonist. GnRH antagonists block GnRH receptors by competitive binding resulting in immediate gonadotrophin suppression, which enables a short treatment regimen for ovarian simulation. Ganirelix has high aqueous solubility and is an active ingredient added into the drugs and has been developed for the treatment the infertility including situations artificial egg retrieval, fertilization and implantation.
Pharmacologic action
GnRH stimulates the synthesis and secretion of LH and follicle-stimulating hormone (FSH). The LH pulse frequency in the middle and late stages of the follicular phase is approximately once per hour. These pulses are reflected in the transient rise in serum LH. In the mid-menstrual period, a large release of GnRH caused a surge in LH. LH surges in the mid-menstrual period can cause several physiological responses, including: ovulation, oocyte meiosis recovery, and corpus luteum formation. Luteal formation causes an increase in serum progesterone levels, while estradiol levels decrease. Ganirelix is a GnRH antagonist that competitively blocks the GnRH receptor on pituitary gonadoblasts, and the subsequent transduction pathway. It produces a rapid, reversible inhibition of gonadotropin secretion. The inhibitory effect of ganirelix on the secretion of LH in the pituitary gland is stronger than that on FSH. Ganirelix does not cause the first release of endogenous gonadotropin, which is consistent with antagonism.
Function
Ganirelix can inhibit ovulation, oocyte maturation and lutealization. Especially, for women with ovarian hyperstimulation, it can prevent LH fluctuations and related stimuli, and increase the ratio of implantation and pregnancy. Owing to the special properties and advantages of ganirelix, it can be used for the treatment of infertility including situations artificial egg retrieval, fertilization and implantation. Compared with leuprolide and triptrorlin, ganirelix offers a new treatment regimen in ovarian stimulation that is short, safe, tolerated, optimizing convenience for the patient. Ganirelix is used in women who are receiving the assisted reproductive technology (ART) controlled ovary stimulation (COS) regimen to prevent premature leprotic hormone (LH) peaks.
Pharmacokinetics and metabolism
After a single subcutaneous administration of 0.25 mg of ganirelix to female volunteers abroad, the plasma concentration reached a peak concentration (Cmax) of about 15 ng/ml within 1-2 hours (Tmax), while for healthy Chinese female volunteers, about 1 hour after a single subcutaneous administration of 0.25 mg of ganirelix, the mean plasma concentration was 7.88 ng/ml. Metabolism studies of ganirelix has shown that the main circulating component in plasma is ganirelix, which is also the main compound found in urine, and fecal matter contains only metabolites, the metabolite is a small peptide fragment formed by the enzymatic cleavage of ganirelix at its restriction site.
References:
The European Orgalutran Study Group, Borm G and Mannaerts B. Treatment with the gonadotropin-releasing hormone antagonist ganirelix in women undergoing ovarian simulation with recombinant follicle stimulating hormone is effective, safe and convenient : Results of a controlled, randomised, multicenter trial. Hum Reprod, 2000, 15 (7): 1490-1498.
The European Middle East Orgalutran Study Group. Comparable clinical outcome using the GnRH antagonist ganirelix or a long protocol of the GnRH agonist triptorelin for the, prevention of premature LH surges in women undergoing ovarian stimulation. Hum Reprod, 2001, 16(4): 644-651.
Fluker M, Grifo J, Leader A, Levy M, Meldrum D, Muasher SJ, Rinehart J, Rosenwaks Z, Scott RT Jr, Schoolcraft W, Shapiro DB, North American Ganirelix Study Group. Efficacy and safety of ganirelix acetate versus leuprolide acetate in women undergoing controlled ovarian hyperstimulation. Fertility and Sterility, 2001, 75(1): 38-45.
