The
LHRH agonists are antigonadotropic agents for reversible ovarian suppression in gynaecology and in oncology. In oncology, pituitary inhibition is maintained with high release rates preferably by implant or
microcapsule injection. The pharmacokinetics of
buserelin after injection, infusion, and during implant treatment (controlled release) are described. The release rate is monitored by urinary
buserelin excretion (fractional excretion of 30% of the daily dose). During
therapy,
LHRH agonists in serum are measured by specific radioimmunoassays, with or without extraction. A more convenient non-invasive procedure is to measure the amount of
buserelin in 24-h urine samples (during
injections or
nasal spray), or the urinary
buserelin/
creatinine ratio in morning urine samples (during infusions or implants). After high dose injection,
buserelin has a half-life of 80 min, therapeutic plasma concentrations are maintained for 8-12 h. In long-term maintenance with
buserelin implants (
polylactide-glycolide, 75:25), serum concentrations and urinary excretion showed an extended plateau phase indicating a suitable dose interval of 2-3 months. In
endometriosis and
leiomyoma, the minimum release rate (urinary
buserelin) required for maintenance of
steroid suppression was established (
buserelin excretion of about 0.5 microgram/g
creatinine).
Buserelin implants in prostate
carcinoma are effective for 2 or 3 months, after a single dose of 6.6 or 10 mg
buserelin, respectively. A consistent suppression of serum
testosterone secretion was confirmed for more than 2 yr.
Buserelin microparticles are effective in rhesus monkeys to completely suppress follicular maturation and oestrogen secretion during 4-6 weeks after a single dose of 3.6 mg
buserelin. Recent results on the controlled release of an
LHRH antagonist (
Hoe 013) from biodegradable microparticles in rats with DMBA-induced mammary tumours indicate that tumour suppression by
LHRH antagonists is well tolerated and highly effective. The local tolerance at the injection site of antagonist microparticles is excellent as in the case of
LHRH agonists like
buserelin.