The Effects of Dose and Route on the Toxicokinetics and Disposition of 1-Butyl-3-methylimidazolium Chloride in Male F-344 Rats and Female B6C3F1 Mice

• Published in: Drug metabolism and disposition 2008-02, Vol.36 (2), p.284-293
• Main Authors: Sipes, I.G., Knudsen, G.A., Kuester, R.K.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Dose-Response Relationship, Drug; Drug Administration Routes; Feces - chemistry; Female; Imidazoles - blood; Imidazoles - pharmacokinetics; Imidazoles - urine; Male; Medical sciences; Mice; Mice, Inbred Strains; Pharmacology. Drug treatments; Rats; Rats, Inbred F344; Solvents - pharmacokinetics
• ISSN: 0090-9556; 1521-009X
• DOI: 10.1124/dmd.107.018515

These studies characterize the effect of dose and route of administration on the disposition and elimination of the ionic liquid, 1-butyl-3-methylimidazolium chloride (Bmim-Cl). After i.v. (5 mg/kg) or oral (50 mg/kg) administration to male F-344 rats [14C]Bmim-Cl detected in blood decreased rapidly. Clearance rates from the blood after i.v. and oral administration were similar (7.4 and 11.9 ml/min, respectively). Systemic bioavailability was determined to be 62.1% of a 50 mg/kg dose in rats. Urinary excretion of the parent compound by rats was the major route of elimination (i.v.: 91% in 24 h; oral: 55–74% in 24 h). The rates and routes of elimination were not affected by escalation of dose (0.5–50 mg/kg) or repeated oral administration (five daily administrations, 50 mg/kg) and were similar in male rats and B6C3F1 female mice (86–95% of dose eliminated in 24 h). Apparent systemic exposure to Bmim-Cl after dermal administration was dependent upon vehicle, as assessed by the percentage of dose eliminated in urine after application in a particular vehicle (water: 1%; ethanol/water: 3%; and dimethylformamide/water: 13% of dose). Regardless of gender, species, dose, route, or number of exposures, high-pressure liquid chromatography-UV/visible-radiometric analyses of urine samples showed a single peak that coeluted with the Bmim-Cl standard. These studies illustrate that systemic bioavailability of Bmim-Cl is high, tissue disposition and metabolism are negligible, and absorbed compound is extensively extracted by the kidney and eliminated in the urine as the parent compound.