1. DB06719
Buserelin
C62H90N16O15

2. DESCRIPTION
Buserelin is a synthetic peptide analog of the luteinizing hormone-releasing hormone (LHRH) agonist, which stimulates the pituitary gland’s gonadotrophin-releasing hormone receptor (GnRHR). It is used in prostate cancer treatment.
INDICATION
Buserelin may be used in the treatment of hormone-responsive cancers such as prostate cancer or breast cancer, estrogen-dependent conditions (such as endometriosis or uterine fibroids), and in assisted reproduction.

3. PHARMACODYNAMICS
The substitution of glycine in position 6 by D-serine, and that of glycinamide in position 10 by ethylamide, leads to a nonapeptide with a greatly enhanced LHRH effect. The effects of buserelin on FSH and LH release are 20 to 170 times greater than those of LHRH. Buserelin also has a longer duration of action than natural LHRH. Investigations in healthy adult males and females have demonstrated that the increase in plasma LH and FSH levels persist for at least 7 hours and that a return to basal values requires about 24 hours. Clinical inhibition of gonadotropin release, and subsequent reduction of serum testosterone or estradiol to castration level, was found when large pharmacologic doses ( mcg SC/day or mcg IN/day) were administered for periods greater than 1 to 3 months. Chronic administration of such doses of buserelin results in sustained inhibition of gonadotropin production, suppression of ovarian and testicular steroidogenesis and, ultimately, reduced circulating levels of gonadotropin and gonadal steroids. These effects form the basis for buserelin use in patients with hormone-dependent metastatic carcinoma of the prostate gland as well as in patients with endometriosis.

4. MECHANISM OF ACTION
Buserelin stimulates the pituitary gland's gonadotrophin-releasing hormone receptor (GnRHR). Buserelin desensitizes the GnRH receptor, reducing the amount of LH and testosterone. However, there is a concomitant surge in LH and testosterone levels with the decrease in androgens, so antiandrogens must administered.
ROUTE OF ELIMINATION
Following a single IV dose of radiolabelled aprotinin, approximately 25-40% of the radioactivity is excreted in the urine over 48 hours. After a 30 minute infusion of 1 million KIU, about 2% is excreted as unchanged drug. After a larger dose of 2 million KIU infused over 30 minutes, urinary excretion of unchanged aprotinin accounts for approximately 9% of the dose.

5. TARGET
Lutropin-choriogonadotropic hormone receptor,
Gonadotropin-releasing hormone receptor
ABSORPTION
Buserelin is water soluble and readily absorbed after subcutaneous injection (70% bioavailable). However, bioavailability after oral absorption. When administered correctly via the nasal route, it may be absorbed in the nasal mucosa to achieve sufficient plasma levels.
VOLUME OF DISTRIBUTION
Buserelin circulates in serum predominantly in intact active form. Preferred accumulation is preferentially in the liver and kidneys as well as in the anterior pituitary lobe, the biological target organ.
PROTEIN BINDING 15%

6. METABOLISM
It is metabolized and subsequently inactivated by peptidase (pyroglutamyl peptidase and chymotrypsin-like endopeptidase) in the liver and kidneys as well as in the gastrointestinal tract. In the pituitary gland, it is inactivated by membrane-located enzymes.
ROUTE OF ELIMINATION
Buserelin and its inactive metabolites are excreted via the renal and biliary routes. In man it is excreted in urine at 50% in its intact form.
Half life The elimination half-life is approximately 50 to 80 minutes following intravenous administration, 80 minutes after subcutaneous administration and approximately 1 to 2 hours after intranasal administration.
TOXICITY
Buserelin may induce early, transient increase in serum testosterone or estradiol which can lead in the exacerbation of signs and symptoms of metastatic prostate cancer or endometriosis. Adverse reactions reported at more than 10% occurrence include headache, loss of libido in patients with prostate cancer, hot flashes, hypermenorrhea, decreased libido in prostate cancer and endometriosis, flatulence, impotence, vaginal dryness, back pain and nasal mucosa irritation.

7. Cinnafact/Suprefact Injectable/Implant/Spray
Buserelin is used to treat cancer of the prostate gland.
It is similar to a hormone normally released from the hypothalamus gland. When given regularly, buserelin decreases testosterone levels. Reducing the amount of testosterone in the body is one way of treating cancer of the prostate.

8. DOSAGE:
For prostate cancer:
For nasal dosage forms:
Adults: 200 micrograms (mcg) (2 sprays) into each nostril every eight hours.
For injection dosage forms:
Adults: In the beginning, 500 mcg (0.5 milligrams [mg]) injected under the skin every eight hours. After a time, your doctor may lower your dose to 200 mcg (0.2 mg) once a day.
ADVERSE REACTION:
Bone pain, numbness or tingling of the hands or feet, trouble with urinating, weakness in the legs

9. DRUG INTERACTIONS
Capromab
Avoid combination because luteinizing Hormone-Releasing Hormone Analogs may diminish the diagnostic effect of Indium 111 Capromab Pendetide.
Mifepristone
Buserelin moderately contributes to Q-Tc prolongation. Combination must be avoided because mifepristone can further enhance that effect.

10. REFERENCES
Lexicomp. Buserelin Acetate. N.p., Web. 11 Nov. 2014
Sanofi-Aventis Canada Inc. Buserelin Acetate. 1st ed Web. 11 Nov
Kirby RS, Fitzpatrick JM, Clarke N: Abarelix and other gonadotrophin-releasing hormone antagonists in prostate cancer. BJU Int Dec;104(11):1580-4