| 药品名称 |
Degarelix
|
| 分子靶点 |
Gonadotropin-releasing hormone receptor
|
| 药物类型 |
Small Molecule
|
| 研发阶段 |
Approved
|
| 药物描述 |
Degarelix is used for the treatment of advanced prostate cancer. Degarelix is a synthetic peptide derivative drug which binds to gonadotropin-releasing hormone (GnRH) receptors in the pituitary gland and blocks interaction with GnRH. This antagonism reduces luteinising hormone (LH) and follicle-stimulating hormone (FSH) which ultimately causes testosterone suppression. Reduction in testosterone is important in treating men with advanced prostate cancer. Chemically, it is a synthetic linear decapeptide amide with seven unnatural amino acids, five of which are D-amino acids. FDA approved on December 24, 2008.
|
| 结构式 |
 |
| 药物别名 |
Degarelix
|
| 治疗类别 |
Amino Acids, Peptides, and Proteins;Antineoplastic Agents;Antineoplastic and Immunomodulating Agents;Endocrine Therapy;Gonadotropin-releasing Hormone Antagonists;Gonadotropin-Releasing Hormone, antagonists & inhibitors;Hormone Antagonists and Related Agents;Peptides;Potential QTc-Prolonging Agents;QTc Prolonging Agents
|
| UNII号 |
SX0XJI3A11
|
| CAS号 |
214766-78-6
|
| 分子量 |
1632.29
|
| 分子式 |
C82H103ClN18O16
|
| 适应症 |
Degaralix is used for the management of advanced prostate cancer.
|
| 药效学 |
Degarelix is a synthetic derivative of GnRH decapeptide, the ligand of the GnRH receptor. Gonadotropin and androgen production result from the binding of endogenous GnRH to the GnRH receptor. Degarelix antagonizes the GnRH receptor which in turn blocks the release of LH and FSH from the pituitary. LF and FSH decreases in a concentration-dependent manner. The reduction in LH leads to a decrease in testosterone release from the testes.
|
| 作用机制 |
Degarelix competitively inhibits GnRH receptors in the pituitary gland, preventing the release of luteinizing hormone (LH) and follicle stimulating hormone. Reduced LH suppresses testosterone release, which slows the growth and reduces the size of prostate cancers.
|
| 吸收 |
Degarelix forms a depot at the site of injection after subcutaneous administration from which the drug slowly released into circulation. After a single bolus dose of 2mg/kg, peak plasma concentrations of degarelix occured within 6 hours at a concentration of 330 ng/mL.Ki = 0.082 ng/mL and 93% of receptors were fully suppressed;MRT = 4.5 days.
|
| 分布量 |
Central compartment: 8.88 - 11.4 L;Peripheral compartment: 40.9 L
|
| 蛋白结合 |
90% of the drug is bound to plasma proteins.
|
| 代谢 |
70% - 80% of degarelix is subject to peptide hydrolysis during its passage through the hepatobiliary system and then fecally eliminated. No active or inactive metabolites or involvement of CYP450 isozymes.
|
| 排泄 |
Fecal (70% to 80%) and renal (20%-30% of unchanged drug)
|
| 半衰期 |
Terminal half-life: 41.5 - 70.2 days;Absorption half-life: 32.9 hours;Half-life from injection site: 1.17 days.
|
| 清除 |
Following subcutaneous administration of degarelix to prostate cancer patients the clearance is approximately 9 L/hr.
|
| 毒理 |
The most commonly observed adverse reactions (> 10%) during degarelix therapy included injection site reactions (e.g., pain, erythema, swelling, or induration), hot flashes, increased weight, and increases in serum levels of transaminases and gamma-glutamyltransferase (GGT).
|
| ATC代码 |
L02BX02
|
