Disposition of nafarelin acetate, a potent agonist of luteinizing hormone-releasing hormone, in rats and rhesus monkeys

Journal Article · Sun Sep 01 04:00:00 EDT 1985 · Drug Metab. Dispos.; (United States)

OSTI ID:6041140

Chu, N I; Chan, R L; Hama, K M; Chaplin, M D

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), Journal Name: Drug Metab. Dispos.; (United States) Vol. 5; ISSN DMDSA
• Country of Publication: United States
• Language: English

Related Subjects

551001* -- Physiological Systems-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ACETATES
ANIMALS
BODY
CARBON 14 COMPOUNDS
CARBOXYLIC ACID SALTS
DIGESTIVE SYSTEM
DISTRIBUTION
GASTROINTESTINAL TRACT
GLANDS
HORMONES
INTESTINES
KIDNEYS
KINETICS
LABELLED COMPOUNDS
LH-RH
LIBERINS
LIVER
MAMMALS
MONKEYS
ORGANIC COMPOUNDS
ORGANS
PEPTIDE HORMONES
PHARMACOLOGY
PITUITARY HORMONES
PRIMATES
PROTEINS
RATS
RODENTS
TISSUE DISTRIBUTION
TRITIUM COMPOUNDS
VERTEBRATES