Buserelin

Synonyms :
(Des-Gly10,D-Ser(tBu)6,Pro-NHEt9)-LHRH, D-Ser(Tbu)6EA10LHRH, Etilamide, Tiloryth

Status : approved

Therapeutic Classification

HORMONES AND RELATED AGENTS

ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ENDOCRINE THERAPY
HORMONES AND RELATED AGENTS

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.

Used

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.

Mechanism Of Action

Buserelin stimulates the pituitary gland’s gonadotrophin-releasing hormone receptor (GnRHR). Buserelin desensitizes the GnRH receptor, reducing the amount of gonadotropin. In males, this results in a reduction in the synthesis and release of testosterone. In females, estrogen secretion is inhibited. While initially, there is a rise in FSH and LH levels, chronic administration of Buserelin results in a sustained suppression of these hormones.

Dosage

Form Route Strength
Solution nasal 1 mg
Solution subcutaneous 1 mg
Implant subcutaneous 6.3 mg
Implant subcutaneous 9.45 mg
Liquid subcutaneous 1 mg
Spray nasal 1 mg
Liquid nasal 1 mg

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.

Toxic Effect

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.

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.

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.

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.

Protein Binding

15%

Elimination Route

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.

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.

Chemical Classification

Peptides

Organic Compounds

Organic Acids

Carboxylic Acids and Derivatives

Amino Acids, Peptides, and Analogues

Salt : Buserelin acetate

Chemical Name

(Des-Gly10,D-Ser(tBu)6,Pro-NHEt9)-LHRH

Brands

name Dosage form Country
Suprefact solution Canada
Suprefact solution Canada
Suprefact Depot 2 Months implant Canada
Suprefact Depot 3 Months implant Canada
Suprefact Inj 1mg/ml liquid Canada
Suprefact Intranasal Solution 1mg/ml spray Canada
Suprefact Liq 1mg/ml liquid Canada

Drug Drug Interactions

  •  Acetohexamide  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Alogliptin  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Canagliflozin  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Chlorpropamide  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Corifollitropin Alfa  : Luteinizing Hormone-Releasing Hormone Analogs may enhance the therapeutic effect of Corifollitropin Alfa.
  •  Gliclazide  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Glimepiride  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Gliquidone  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Glyburide  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Insulin Aspart  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Insulin Detemir  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Insulin Glargine  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Insulin Glulisine  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Insulin Lispro  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Insulin Regular  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Insulin, isophane  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Linagliptin  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Metformin  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Mifepristone  : May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying).
  •  Repaglinide  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Saxagliptin  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Tolbutamide  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Vildagliptin  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.

Calculated Property

kind Value Source

Affected organism

Humans and other mammals

Target within organism

  • Lutropin-choriogonadotropic hormone receptor : in Human
  • Gonadotropin-releasing hormone receptor : in Human