Abarelix Acetate

Abarik is an artificially synthesized peptide compound with the molecular formula C ₇₂ H ₉₅ ClN ₁₄ O ₁₄, and a molecular weight of 1416.08. It appears as a white to off white powder with a purity of 95% to 99%, and can be analyzed by HPLC-DAD method. Abarek has a high plasma protein binding rate (96%~99%) and is widely distributed in the body, with a terminal apparent distribution volume of 4040 ± 1607L. Its metabolism is mainly carried out through peptide bond hydrolysis, and there is no evidence to suggest that cytochrome P450 is involved in its metabolic process.

After intramuscular injection in the human body, about 13% of the prototype drug is excreted with urine, and no other metabolites are detected in the urine. The renal clearance rate of 100mg injection is 14.4L/d (or 10mL/min). These characteristics provide the basis for the pharmacological effects and metabolic clearance of Abarik in the body.

Due to its binding to the GnRH acceptor, which blocks the signal transduction of GnRH, the secretion of LH and FSH by the anterior pituitary gland is inhibited. The decreased secretion of LH and FSH directly affects the function of the gonads. In males, the testicles are the main gonads, and LH is a key hormone that stimulates testicular interstitial cells to secrete testosterone.

When LH secretion decreases, the ability of testicular interstitial cells to synthesize and secrete testosterone decreases, leading to a decrease in plasma testosterone concentration. Similarly, FSH also has a significant impact on the spermatogenic function of the testes. Reduced FSH secretion can affect sperm production, but in the treatment of prostate cancer, the main focus is on reducing testosterone levels.

Prostate cancer is an androgen dependent tumor, and testosterone and other androgens play an important promoting role in the occurrence, development, and progression of prostate cancer. Testosterone can activate a series of signaling pathways by binding to androgen acceptors inside prostate cancer cells, promoting cancer cell proliferation, survival, and metastasis. Therefore, reducing testosterone levels in the body is one of the important strategies for treating prostate cancer.

Abarek effectively reduces the ability of the testes to secrete testosterone by inhibiting the secretion of LH and FSH, resulting in a significant decrease in plasma testosterone concentration. This effect of reducing testosterone levels is called castration, similar to surgical removal of the testicles (surgical castration) or the use of drugs to inhibit testicular function (drug castration). Compared with traditional GnRH agonists, it has unique advantages.

Traditional GnRH agonists can cause a brief increase in LH and FSH levels during initial use, leading to an initial increase followed by a decrease in testosterone levels, a process known as rebound. During the stage of elevated testosterone levels, it may stimulate the growth and spread of prostate cancer cells, leading to a brief deterioration of the condition. As a GnRH antagonist, it directly inhibits LH secretion without causing a rebound in testosterone levels, and can rapidly reduce testosterone levels, thereby more effectively controlling the progression of prostate cancer.

For example, in a clinical study of patients with advanced symptomatic prostate cancer, 15 patients with bone metastases experienced pain relief after 12 weeks of treatment, and the efficacy, dosage, and frequency of using anesthetic analgesics decreased; Thirteen patients who had bladder outlet obstruction and had bladder drainage tubes inserted, 10 of whom had their drainage tubes removed after 12 weeks; Among the 8 patients with spinal or epidural metastases but no neurological symptoms, no one showed neurological damage symptoms.

Palliative treatment: mainly used for the palliative treatment of advanced symptomatic prostate cancer (PCA) that is not suitable for receiving luteinizing hormone releasing hormone (LHRH) agonist therapy and refuses surgical resection, and has one or more of the above conditions. The purpose of palliative care is to alleviate the pain of patients, improve their quality of life, and prolong survival by effectively controlling the progression of prostate cancer, providing an important treatment option for these patients.