Cetrorelix

Cetrorelix
Systematic (IUPAC) name
Acetyl-D-3-(2′-naphtyl)-alanine-D-4-chlorophenylalanine-D-3-(3′-pyridyl)- alanine-L-serine-L-tyrosine-D-citrulline-L-leucine-L-arginine-L-proline-D-alanine-amide
Clinical data
Trade names Cetrotide
AHFS/Drugs.com Micromedex Detailed Consumer Information
  • US: X (Contraindicated)
Subcutaneous injection
Pharmacokinetic data
Bioavailability 85%
Protein binding 86%
Half-life 62.8 hours / 3mg single dose; 5 hours / 0.25 mg single dose; 20.6 hours / 0.25mg multiple doses
Excretion feces (5% to 10% as unchanged drug and metabolites); urine (2% to 4% as unchanged drug)
Identifiers
120287-85-6 Yes
H01CC02
PubChem CID 16130924
DrugBank DB00050 Yes
ChemSpider 10482082 Yes
UNII OON1HFZ4BA Yes
KEGG D07665 Yes
ChEBI CHEBI:59224 Yes
ChEMBL CHEMBL1200490 
Chemical data
Formula C70H92ClN17O14
1431.06 g/mol
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Cetrorelix acetate (trade name Cetrotide) is an injectable gonadotropin-releasing hormone antagonist (GnRH antagonist). A synthetic decapeptide, it is used to treat hormone-sensitive cancers of the prostate and breast (in pre-/perimenopausal women) and some benign gynaecological disorders (endometriosis, uterine fibroids and endometrial thinning). In addition, cetrorelix is used in assisted reproduction to inhibit premature luteinizing hormone surges. The drug works by blocking the action of GnRH upon the pituitary, thus rapidly suppressing the production and action of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). It is administered as either multiple 0.25 mg daily subcutaneous injections or as a single-dose 3 mg subcutaneous injection. The duration of the 3 mg single dose is four days; if hCG is not administered within four days, a daily 0.25 mg dose is started and continued until hCG is administered.

Use in IVF

Cetrorelix is marketed by Merck Serono for use in in-vitro fertilization in all countries except Japan, where it is marketed by Shionogi and Nippon Kayaku.[1] Aeterna Zentaris receives royalties on these sales and retains rights to develop cetrorelix for other indications. In IVF use it is injected daily after follicle stimulation has been initiated and evidence of follicle maturation is approaching; given daily it prevents an endogenous LH surge that would trigger an untimely ovulation prior to the hCG administration by the treating physician. As an alternative to the GnRH antagonist, also a GnRH agonist could be given, but agonist have to be started earlier to overcome the agonistic effect. Cetrorelix can be mixed with follitropin alpha without compromising their reported safety and efficacy.[2]

Implications

Over a period of 3 weeks, daily injections of cetrorelix were administered to 12 men in order to suppress testosterone levels. Testosterone levels were significantly suppressed as compared to a control group. During this time of suppression, increases in high density lipoproteins (HDLs) were seen. HDLs are responsible for removing cholesterol from the blood and higher amounts are correlated with increased cardivascular health.[3]

Contraindications

The use of cetrorelix is contraindicated in severe renal impairment. It is not intended for women aged 65 years or older. Use in women with severe allergic conditions is not recommended. Use with caution in women with active allergies or history of allergies.

References

  1. ↑ Aeternia Zentaris product page
  2. ↑ Lin, Y.; Wen, Y.; Chang, Y.; Seow, K.; Hsieh, B.; Hwang, J.; Tzeng, C. (2010). "Safety and efficacy of mixing cetrorelix with follitropin alfa: a randomized study". Fertility and Sterility 94 (1): 179–183. doi:10.1016/j.fertnstert.2009.02.062. PMID 19339001.
  3. ↑ von Eckardstein, A (1997). "Suppression of Endogenous Testosterone in Young Men Increases Serum Levels of High Density Lipoprotein Subclass Lipoprotein A-I and Lipoprotein(a)". Journal of Clinical Endocrinology 82 (10): 3367.