Disposition of nafarelin acetate, a potent agonist of luteinizing hormone-releasing hormone, in rats and rhesus monkeys
Nafarelin acetate, (6-(3-(2-naphthyl)-D-Ala))-luteinizing hormone-releasing hormone (LHRH), is a synthetic LHRH agonist. In the suppression of estrus in female rats, nafarelin acetate was about 200 times as potent as LHRH. The authors have studied the distribution and excretion of radiolabeled nafarelin acetate administered iv to rats and rhesus monkeys and have also compared the pharmacokinetics of nafarelin acetate to LHRH in these two species. Distribution of a single 100-micrograms dose ( UC)nafarelin acetate into tissues in male rats was rapid and of the 13 tissues assayed, highest concentrations of radioactivity were observed in the kidneys, liver, and intestines. The urine to feces ratio of nafarelin-associated UC was 4:1 in rhesus monkeys and 1:3 in rats. Nafarelin acetate and LHRH given iv to female rhesus monkeys in approximately equimolar doses had terminal plasma t1/2 values of 120 min and 33 min, and systemic clearance values of 2.7 ml/min/kg and 31.4 ml/min/kg, respectively. In female rats, the plasma t1/2 was 33.6 min for nafarelin acetate and 6.7 min for LHRH, and the systemic clearance values for nafarelin acetate and LHRH were 12.0 ml/min/kg and 57.6 ml/min/kg, respectively, after approximately equimolar doses.
- Research Organization:
- Syntex Research, Palo Alto, CA
- OSTI ID:
- 6041140
- Journal Information:
- Drug Metab. Dispos.; (United States), Vol. 5
- Country of Publication:
- United States
- Language:
- English
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LH-RH
PHARMACOLOGY
TISSUE DISTRIBUTION
PROTEINS
ACETATES
CARBON 14 COMPOUNDS
INTESTINES
KIDNEYS
KINETICS
LIVER
MONKEYS
RATS
TRITIUM COMPOUNDS
ANIMALS
BODY
CARBOXYLIC ACID SALTS
DIGESTIVE SYSTEM
DISTRIBUTION
GASTROINTESTINAL TRACT
GLANDS
HORMONES
LABELLED COMPOUNDS
LIBERINS
MAMMALS
ORGANIC COMPOUNDS
ORGANS
PEPTIDE HORMONES
PITUITARY HORMONES
PRIMATES
RODENTS
VERTEBRATES
551001* - Physiological Systems- Tracer Techniques