buserelin (Suprecur)

Indications

• palliative treatment of prostate cancer, usually in combination with other agents
• management of endometriosis

Dosage

• endometriosis:
  • 300-400 ug TID intranasally
  • 200 ug SC QD
• prostate cancer:
  • 1500 ug SC QD for 3-7 days, then
    • 1200 ug QD intranasally, or
    • 200 ug SC QD
  • depot injections of 6.6 & 10 mg under investigation
  • used in combination with androgen antagonist bicalutamide (Casodex)

Pharmacokinetics

• bioavailability of intranasal form is 3%
• peak serum levels within 11 hours of intranasal or SQ administration
• protein binding is 15%
• metabolized primarily to buserelin 5-9 which is inactive
• 1/3 eliminated in urine, 2/3 as intact buserelin
• 1/2life 75 minutes, prolonged with renal insufficiency

elimination via liver

1/2life = 75 minutes

Adverse effects

• local discomfort at the injection site
• hot flashes
• decreased libido
• headache
• vaginal dryness
• depression
• emotional lability
• nausea
• weight gain
• breast pain
• premenstrual syndrome
• fatigue
• dizziness
• loss of bone mineral density
• tumor flare (mostly in 1st 2 weeks due to initial stimulation of hormone production)
• pulmonary fibrosis (rare)

• drug adverse effects of GnRH agonists

Mechanism of action

• GnRH analog (nonapeptide, i.e. 9 residues)
• affects LH & FSH release from the pituitary
  • initially stimulates LH & FSH release, then
  • diminishes LH & FSH release via negative feed-back (loss of pulsatility)
• decline in testosterone & estradiol production
• causes chemical castration
• retards growth of hormone-sensitive tissue

More general terms

• synthetic peptide
• gonadotropin-releasing hormone agonist (GnRH analog)
• antineoplastic agent (chemotherapeutic agent)

Additional terms

• prostate cancer

Database

• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=50224
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=50225