Metabolic disposition of [14C]-trimethylamine N-oxide in rat: variation with dose and route of administration.

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.