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.
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 [(14)C]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.
Sipes
I G
IG
Department of Pharmacology, College of Medicine, The University of Arizona, P.O. Box 245050, Tucson, AZ 85724-5050, USA. sipes@email.arizona.edu
Knudsen
G A
GA
Kuester
R K
RK
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D005243:Feces / Q000737:chemistry; D005260:Female; D007093:Imidazoles / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D051381:Rats; D011916:Rats, Inbred F344; D012997:Solvents / Q000493:pharmacokinetics
D007093:Imidazoles; D012997:Solvents; C502841:1-butyl-3-methylimidazolium chloride