Pharmacokinetics of trimethylamine in rats, including the effects of a synthetic diet

1. The pharmacokinetic profile of trimethylamine (TMA) was examined in the male Wistar rat and the effects of a synthetic diet on TMA pharmacokinetics were also evaluated. 2. The concentrations of TMA and its N-oxide in blood were analysed by a se nsitive headspace gas chromatographic assay. 3. The pharmacokinetics of TMA were essentially linear for intravenous (i.v .) bolus doses of 10-40 mg kg(-1). Over the range of administered i.v. dose s, the concentrations of TMA in blood declined approximately monoexponentia lly with half-lives of 2.03-2.48 h. The V-d of TMA ranged from 3.2 to 4.39 l kg(-1) and clearance ranged from 18.78 to 23.92 ml min(-1) kg(-1). The pe ak concentration of TMA in blood occurred at 1 h after oral administration of a 20 mg kg(-1) dose and the bioavailability for the oral dose averaged 8 1%. 4. Peak concentrations of trimethylamine N-oxide (TMAO) in blood were attai ned at 0.75 and 1 h after i.v and oral administration of TMA (20 mg kg(-1)) , respectively. 5. Feeding the male Wistar rat with a synthetic diet resulted in a twofold decrease in the clearance of TMA. Furthermore, the concentration of TMAO in blood after i.v. administration of TMA peaked at 1.25 h in rat placed on t he synthetic diet as opposed to 0.75 h in rat placed on normal laboratory r at chow. The altered pharmacokinetic profile of TMA and its N-oxide suggest a diminished drug-elimination capacity in rat placed on the synthetic diet . 6. Dietary modulation of flavin-containing monooxygenase (FMO) activity may explain the effects of diet on the pharmacokinetics of TMA and its N-oxide .