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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

Department of Pharmacology, College of Medicine, the University of Arizona, Tucson, Arizona

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.