Biotransformation of /sup 14/C-lidamidine in the rat, Cynomolgus monkey and man

Conference · Sat Mar 01 00:00:00 EST 1986 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:5450102

Bordeaux, K G; Studt, W L; Berger, P L; Kullberg, M P; Meacham, R H

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-; TRN: 86-028439
• Journal Information: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Vol. 45:3; Conference: 70. annual meeting of the Federation of American Society for Experimental Biology, St. Louis, MO, USA, 13 Apr 1986
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
62 RADIOLOGY AND NUCLEAR MEDICINE
AMIDINES
METABOLISM
CARBON 14 COMPOUNDS
EXCRETION
LIQUID COLUMN CHROMATOGRAPHY
MAN
MASS SPECTROSCOPY
METABOLITES
MONKEYS
NUCLEAR MAGNETIC RESONANCE
RATS
TRACER TECHNIQUES
URINE
ANIMALS
BIOLOGICAL MATERIALS
BIOLOGICAL WASTES
BODY FLUIDS
CHROMATOGRAPHY
CLEARANCE
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAGNETIC RESONANCE
MAMMALS
MATERIALS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PRIMATES
RESONANCE
RODENTS
SEPARATION PROCESSES
SPECTROSCOPY
VERTEBRATES
WASTES
550501* - Metabolism- Tracer Techniques
550600 - Medicine