Serum concentration and urinary excretion of the luteinizing hormone-releasing hormone agonist buserelin in patients with endometriosis.
We studied the pharmacokinetics of iv and intranasally administered buserelin, a LHRH agonist peptide, in 14 women with endometriosis. Serum and urinary buserelin concentrations were determined by specific RIA (buserelin antiserum AS-639). Intact buserelin and the metabolites in urine were separated by reverse phase high performance liquid chromatography and measured by RIA. The mean serum buserelin concentrations were 101 +/- 33 (+/- SD) ng/mL 20 min and 1.12 +/- 0.12 ng/mL 360 min after its iv injection in 6 women, and the mean elimination half-life between 20 and 360 min was 51 min. In serum, intact buserelin was the main constituent (10 min, 90%; 120 min, 74%; 360 min, 52%), and the major metabolite was the buserelin-(5-9) pentapeptide (10 min, 0.6%; 120 min, 19%; 360 min, 12%). In the urine collected 0-1 h after buserelin administration, intact buserelin was 66% and the 5-9 pentapeptide was 28% of the total excretion. In the urine collected between 6-24 h after buserelin administration, intact buserelin accounted for 67% and the 5-9 pentapeptide for 32% of the total excretion. The urinary buserelin concentration was 1345 +/- 156 micrograms/g creatinine 1 h and 25 +/- 5 micrograms/g creatinine 6-24 h after buserelin administration. Serum LH, FSH, and estradiol concentrations increased acutely up to 10-fold above basal values; the mean peak LH, FSH, and estradiol values occurred at 180-240 min, 240 min, and 24 h, respectively. In therapeutic studies with buserelin nasal spray in 5 women, serum concentrations of 0.9-1.4 ng/mL were found 15 min after a single dose of 300 micrograms, intranasally, and the urinary excretion was 2.52-3.68 micrograms/24 h during daily administration of 3 doses of 300 micrograms at intervals of 8 h. These results confirm that buserelin is slowly inactivated and remains available to pituitary receptors for a prolonged period after its iv or intranasal administration.
Kiesel
L
L
Division of Gynecological Endocrinology, University of Heidelberg, West Germany.
Sandow
J
J
Bertges
K
K
Jerabek-Sandow
G
G
Trabant
H
H
Runnebaum
B
B
D000281:Administration, Intranasal; D000328:Adult; D001682:Biological Availability; D002064:Buserelin / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D004715:Endometriosis / Q000378:metabolism*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors*; D006801:Humans; D007275:Injections, Intravenous; D007986:Luteinizing Hormone / Q000378:metabolism; D011863:Radioimmunoassay
D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D002064:Buserelin