The relation between pharmacokinetics and endocrine effects of buserelin implants in patients with mastalgia.
Six patients with mastalgia were treated with polylactide/glycolide 50:50 implants containing 6.6 mg buserelin once every 4 weeks, to study the relationship between buserelin pharmacokinetics and suppression of pituitary-ovarian function. On the first treatment day there was an initial rise in plasma and urinary buserelin levels followed by a rapid fall during the next 2 days. After a plateau phase (60-80 micrograms/g creatinine) urinary buserelin/creatinine ratios decreased slowly to a mean value of 25 micrograms/g creatinine 4 weeks after implantation. Plasma oestradiol concentrations dropped to castrate values within 2 weeks of treatment reaching a mean concentration of 17 pmol/l compared to 27 pmol/l (P less than 0.01) determined in 680 postmenopausal control women. After the last implant injection urinary buserelin/creatinine ratios remained relatively high (greater than 5 micrograms/g creatinine) during more than 8 weeks followed by an exponential decrease (half-life of buserelin release: 15 days) to undetectable buserelin levels at 16-22 weeks after the last implantation. A rise of suppressed plasma oestradiol concentrations to above castrate levels was found 15-20 weeks after the last buserelin implantation, at a time when urinary buserelin excretion had decreased below 0.2 micrograms/g creatinine. It is concluded that after initial suppression of pituitary-ovarian function only very low concentrations of buserelin are needed to maintain suppression of ovarian activity by using slow release preparations.
Klijn
J G
JG
Division of Endocrine Oncology (Department of Medical Oncology), Dr Daniel den Hoed Cancer Center, Rotterdam, The Netherlands.
van Geel
B
B
de Jong
F H
FH
Sandow
J
J
Krauss
B
B
D000328:Adult; D001941:Breast Diseases / Q000188:drug therapy*; D002064:Buserelin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D003864:Depression, Chemical; D004343:Drug Implants; D004958:Estradiol / Q000097:blood; D005260:Female; D006207:Half-Life; D006801:Humans; D010053:Ovary / Q000187:drug effects*; D010146:Pain / Q000188:drug therapy*; D010902:Pituitary Gland / Q000187:drug effects*
D004343:Drug Implants; D004958:Estradiol; D002064:Buserelin