Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1   Pharmacodynamic properties
Pharmacotherapeutic group: Gonadotropin releasing hormone analogue
ATC code: L02AE01

Buserelin is a highly active analogue of the natural gonadotropin-releasing hormone (gonadorelin; GnRH, LHRH). The initial pharmacological effect of buserelin is to stimulate gonadotropin release and testosterone secretion. This is followed by a progressive decrease in testosterone into the castrate range.

While gonadotropin release is inhibited during continued treatment with buserelin, the secretion of the other pituitary hormones (growth hormone, prolactin, ACTH, TSH) is not directly influenced. The secretion of adrenal steroids remains unchanged.

In terms of removing testosterone stimulation of tumour tissue, buserelin is as effective as orchiectomy in the treatment of prostatic carcinoma.

Pharmacokinetic Properties

5.2   Pharmacokinetic properties

The release of buserelin from the implant is controlled by degradation of the polymer matrix.
The release profile is biphasic; the initial release (tmax <1 day) is followed by a phase with a slow, steady release within the dosing interval of 2 months/3 months (total dose 6.6mg/9.9 mg). The bioavailability of the buserelin implant is approximately 50% following subcutaneous injection. The systemic exposure to buserelin is sufficient to cause suppression of testosterone into the castrate range throughout the dosing interval.

Buserelin circulates in serum predominantly in the unchanged form. Protein binding is about 15%. Based on preclinical data, buserelin accumulates preferably in the liver, kidneys and anterior lobe of the pituitary gland, which is the biological target organ. Buserelin and its inactive metabolites are excreted renally and animal studies also indicate excretion into the bile. In vitro studies have shown that buserelin is inactivated by peptidases (pyroglutamyl 
peptidase and chymotrypsin-like endopeptidases) in the liver and kidneys. In the pituitary gland, receptor-bound buserelin is inactivated by membrane-located enzymes.