buserelin (Suprecur)

Indications: 1) palliative treatment of prostate cancer, usually in combination with other agents 2) management of endometriosis Dosage: 1) endometriosis: a) 300-400 ug TID intranasally b) 200 ug SC QD 2) prostate cancer: a) 1500 ug SC QD for 3-7 days, then -> 1200 ug QD intranasally, or -> 200 ug SC QD b) depot injections of 6.6 & 10 mg under investigation c) used in combination with androgen antagonist bicalutamide (Casodex) Pharmacokinetics: 1) bioavailability of intranasal form is 3% 2) peak serum levels within 11 hours of intranasal or SQ administration 3) protein binding is 15% 4) metabolized primarily to buserelin 5-9 which is inactive 5) 1/3 eliminated in urine, 2/3 as intact buserelin 6) 1/2life 75 minutes, prolonged with renal insufficiency Adverse effects: 1) local discomfort at the injection site 2) hot flashes 3) decreased libido 4) headache 5) vaginal dryness 6) depression 7) emotional lability 8) nausea 9) weight gain 10) breast pain 11) premenstrual syndrome 12) fatigue 13) dizziness 14) loss of bone mineral density 15) tumor flare (mostly in 1st 2 weeks due to initial stimulation of hormone production) 16) pulmonary fibrosis (rare) Mechanism of action: 1) GnRH analog (nonapeptide, i.e. 9 residues) 2) affects LH & FSH release from the pituitary a) initially stimulates LH & FSH release, then b) diminishes LH & FSH release via negative feed-back (loss of pulsatility) 3) decline in testosterone & estradiol production 4) causes chemical castration 5) retards growth of hormone-sensitive tissue

General

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

Properties

MISC-INFO: elimination route LIVER 1/2life 75 MINUTES

References

DrugDex Drug Evaluation, vol 105, 2000