Biotransformation of /sup 14/C-lidamidine in the rat, Cynomolgus monkey and man
Lidamidine (L) (1-(2,6-dimethylphenyl)-3-methyl-amidinourea) is a novel antidiarrheal agent in animals and man. Studies with /sup 14/C-(L) in rats and monkeys have shown that the drug is well absorbed and excreted in urine primarily as metabolites. Less than 10% of the dose was present as parent compound. HPLC was used for the isolation of metabolites from urine of rats and Cynomolgus monkeys given 10 mg/kg intragastric doses of /sup 14/C-(L). The major metabolite in rats was identified by /sup 1/H NMR and FAB mass spectroscopy as the sulfate cojugate of 3-hydroxylidamidine. Ring hydroxylation of lidamidine followed by Phase II conjugation was the major metabolic pathway in monkeys. Excretion of radioactivity in urine of human volunteers receiving 8 mg doses of /sup 14/C-(L) accounted for 98.2 +/- 0.5 (SD)% of the dose. In contrast to the rat and monkey, urinary elimination of (L) in man accounted for 35.2 +/- 5.3 (SD)% of the dose, and the major metabolite was characterized as N-desmethyllidamidine. Para-hydroxylation on the aromatic ring and/or glucuronidation were insignificant metabolic routes in all three species.
- Research Organization:
- Rorer Group, Inc., Fort Washington, PA
- OSTI ID:
- 5450102
- Report Number(s):
- CONF-8604222-
- Journal Information:
- Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Vol. 45:3; ISSN FEPRA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
550600 -- Medicine
59 BASIC BIOLOGICAL SCIENCES
62 RADIOLOGY AND NUCLEAR MEDICINE
AMIDINES
ANIMALS
BIOLOGICAL MATERIALS
BIOLOGICAL WASTES
BODY FLUIDS
CARBON 14 COMPOUNDS
CHROMATOGRAPHY
CLEARANCE
EXCRETION
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LIQUID COLUMN CHROMATOGRAPHY
MAGNETIC RESONANCE
MAMMALS
MAN
MASS SPECTROSCOPY
MATERIALS
METABOLISM
METABOLITES
MONKEYS
NUCLEAR MAGNETIC RESONANCE
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PRIMATES
RATS
RESONANCE
RODENTS
SEPARATION PROCESSES
SPECTROSCOPY
TRACER TECHNIQUES
URINE
VERTEBRATES
WASTES