Received for publication August 28, 2007.
Revised October 24, 2007.
Accepted for publication October 25, 2007.

The effects of dose and route on the toxicokinetics and disposition of 1-butyl-3-methylimidazolium chloride (Bmim-Cl) in male F-344 rats and female B6C3F1 mice

Abstract

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). Following IV (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 following IV 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 parent compound was the major route of elimination (IV: 89% 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 (5 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 following dermal administration was dependent upon vehicle, as assessed by the percent of dose eliminated in urine after application in a particular vehicle (water: 1%, ethanol/water: 3%, dimethylformamide/water: 13% of dose). Regardless of gender, species, dose, route, or number of exposures, HPLC-UV/Vis-radiometric analyses of urine samples showed a single peak that co-eluted 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 parent compound.

Key words: drug disposition, drug distribution, excretion, toxicokinetics, imidazole drugs

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