Absorption, Disposition and Elimination of 3 Ionic Liquids: Bmim‐Cl, NBuPy‐Cl, and BmPy‐Cl in male F‐344 rats

Abstract

Studies were conducted to characterize the effects of dose and route of administration on the absorption and dispositional fate of three ionic liquids (organic quaternary amines) in male Fischer‐344 rats. The compounds tested were 1‐butyl‐3‐methylimidazolium‐Chloride (Bmim‐Cl), N‐butylpyridinium‐Chloride (NBuPy‐Cl), and 1‐butyl‐3‐methylpyrrolidinium‐Chloride (BmPy‐Cl). Following IV administration (5 mg/kg), radioactivity in blood decreased rapidly in a biphasic manner for all compounds (elimination was >85% of dose in urine). Following oral administration (50 mg/kg), urinary elimination accounted for 78±6% (Bmim‐Cl), 63±11% (NBuPy‐Cl), or 37±10% (BmPy‐Cl) of dose, suggesting differences in the oral absorption among the three compounds. Comparison of blood AUCoral/AUCIV for parent compound revealed systemic oral bioavailabilities of 62.1% (Bmim‐Cl), 67.7% (NBuPy‐Cl), and 43.4% (BmPy‐Cl) of dose. Oral doses of 5 or 0.5 mg/kg resulted in similar elimination patterns. Serial daily oral administration (50 mg/kg, 5 days) of each compound did not alter the absorption or elimination of that compound. Co‐ or pre‐administration of BmPy‐Cl with [14C]‐Bmim‐Cl did not notably alter the rate or route of elimination of [14C]‐Bmim‐Cl. Pharmacokinetic analyses following IV administration for each compound indicated that clearance from blood exceeded the glomerular filtration rate which suggests a role for renal organic cation transporters. It was concluded that while the structures varied, that which was absorbed is extracted by the kidney and eliminated in the urine as parent compound, independent of dose, number of doses, or route of administration. This research was supported by the NIEHS NTP Grant No. N01‐ES‐45529 and NIEHS‐sponsored Southwest Environmental Health Science Center Grant Number P30‐ES‐06694.