title: Metabolic disposition of [14C]-trimethylamine N-oxide in rat: variation with dose and route of administration.
abstract: 1. Urine was the major route of excretion of radioactivity (95% dose in 0-24 h) following the oral, intravenous or intraperitoneal administration of [14C]-trimethylamine N-oxide dihydrate (1 mmol/kg body wt) to the adult male Wistar rat. A further 3-4% was voided in the urine during 24-72 h. Only fractional amounts were detected in the faeces, or were retained within tissues 3 days after administration. 2. Biliary secretion of radioactivity was insignificant (0.18% in 0-4 h) but larger amounts were secreted directly into the lumen of the gastrointestinal tract, especially the small intestine (2.6% in 0-1 h). 3. The only radioactive compounds identified in the urine were trimethylamine N-oxide and dimethylamine. Larger amounts of dimethylamine were excreted following oral administration (10%) as opposed to intravenous (2.5%) or intraperitoneal (1.5%) input. This production of dimethylamine occurred over a 100-fold oral trimethylamine N-oxide dose range (0.3-30 mmol/kg body wt). Incubation of trimethylamine N-oxide with gut contents (especially colon and rectum) led to the formation of dimethylamine.
authors.affiliation: Imperial College School of Medicine at St Mary's, London, UK.
authors.forename: S C
authors.initials: SC
authors.lastname: Mitchell
authors.forename: A Q
authors.initials: AQ
authors.lastname: Zhang
authors.forename: J M
authors.initials: JM
authors.lastname: Noblet
authors.forename: S
authors.initials: S
authors.lastname: Gillespie
authors.forename: N
authors.initials: N
authors.lastname: Jones
authors.forename: R L
authors.initials: RL
authors.lastname: Smith
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001646:Bile / Q000378:metabolism; D002250:Carbon Radioisotopes; D004064:Digestive System / Q000378:metabolism; D004123:Dimethylamines / Q000378:metabolism; D005243:Feces / Q000737:chemistry; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D008297:Male; D008744:Methylamines / Q000008:administration & dosage* / Q000378:metabolism* / Q000652:urine; D009355:Neomycin / Q000494:pharmacology; D016877:Oxidants; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000900:Anti-Bacterial Agents; D002250:Carbon Radioisotopes; D004123:Dimethylamines; D008744:Methylamines; D016877:Oxidants; C034516:dimethylamine; C005855:trimethyloxamine; D009355:Neomycin