DMD Simcyp

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

Drug Metabolism and Disposition Fast Forward
First published on October 29, 2007; DOI: 10.1124/dmd.107.018515

0090-9556/08/3602-284-293$20.00
DMD 36:284-293, 2008

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
dmd.107.018515v1
36/2/284    most recent
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Sipes, I. G.
Right arrow Articles by Kuester, R. K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sipes, I. G.
Right arrow Articles by Kuester, R. K.

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

I. G. Sipes, G. A. Knudsen, and R. K. Kuester

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.

Address correspondence to: Dr. I. Glenn Sipes, Department of Pharmacology, College of Medicine, The University of Arizona, P.O. Box 245050, Tucson, AZ 85724-5050. E-mail: sipes{at}email.arizona.edu




This article has been cited by other articles:


Home page
 Drug Metab. Dispos.Home page
Y. Cheng, S. H. Wright, M. J. Hooth, and I. G. Sipes
Characterization of the Disposition and Toxicokinetics of N-Butylpyridinium Chloride in Male F-344 Rats and Female B6C3F1 Mice and Its Transport by Organic Cation Transporter 2
Drug Metab. Dispos., April 1, 2009; 37(4): 909 - 916.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 2008 by the American Society for Pharmacology and Experimental Therapeutics.