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). 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.
Footnotes
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This research was supported by the National Toxicology Program/National Institute Environmental Health Science (NIEHS) Contract N01-ES-45529. The authors acknowledge the support of the analytical core of the NIEHS-funded Southwest Environmental Health Science Center (P30-ES 06694) and National Cancer Institute Grant (CA023074).
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Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.
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doi:10.1124/dmd.107.018515.
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ABBREVIATIONS: IL, ionic liquid; Bmim-Cl, 1-butyl-3-methylimidazolium chloride; HPLC, high-pressure liquid chromatography; DMF, dimethylformamide; JVC, jugular vein cannula; LC, liquid chromatography; MS, mass spectrometry; UV/Vis, UV-visible; AUC[0–∞], concentration-time curve from time zero to infinity; LOQ, limit of quantification; OCT, organic cation transporters.
- Received August 27, 2007.
- Accepted October 25, 2007.
- The American Society for Pharmacology and Experimental Therapeutics
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