Buserelin DB06719 C 62 H - PowerPoint Presentation

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Buserelin

DB06719

C

62

H

90

N

16

O

15

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.

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 (50-500 mcg SC/day or 300-1200 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.

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.

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%

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.

Cinnafact

/Suprefact

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.

Injectable/Implant/Spray

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

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.

REFERENCES

Lexicomp

.

Buserelin Acetate. N.p

., 2014. Web. 11 Nov.

2014

Sanofi-Aventis Canada Inc. Buserelin

Acetate. 1st ed. 2013. Web. 11 Nov. 2014.http://

www.sanofi.ca

Kirby RS, Fitzpatrick JM, Clarke N:

Abarelix

and other

gonadotrophin

-releasing hormone antagonists in prostate cancer. BJU Int. 2009 Dec;104(11):1580-4

http

://www.ncbi.nlm.nih.gov/pubmed/25293536

http

://www.ncbi.nlm.nih.gov/pubmed/25276180

http

://www.ncbi.nlm.nih.gov/pubmed/24690459

http

://www.ncbi.nlm.nih.gov/pubmed/24657556

http

://www.ncbi.nlm.nih.gov/pubmed/24629591