Nano Archive

Pharmacokinetic evaluation of a 1,3-dicyclohexylurea nanosuspension formulation to support early efficacy assessment

Wahlstrom, Jan L. and Chiang, Po-Chang and Ghosh, Sarbani and Warren, Chad J. and Wene, Steve P. and Albin, Lesley A. and Smith, Mark E. and Roberds, Steven L. (2007) Pharmacokinetic evaluation of a 1,3-dicyclohexylurea nanosuspension formulation to support early efficacy assessment. NANOSCALE RESEARCH LETTERS, 2 (6). pp. 291-296.

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Official URL: http://www.springerlink.com/content/a534j3827k2411...

Abstract

Time and resource constraints necessitate increasingly early decisions to advance or halt pre-clinical drug discovery programs. Early discovery or ``tool'' compounds may be potent inhibitors of new targets, but all too often they exhibit poor pharmaceutical and pharmacokinetic properties that make early assessment of in vivo efficacy difficult. 1,3-Dicyclohexylurea, a potent and selective inhibitor of soluble epoxide hydrolase (sEH), reduces blood pressure in hypertensive preclinical animal models when administered intraperitoneally using DMSO/corn oil as a delivery vehicle. However, the poor aqueous solubility of DCU poses a challenge for in vivo dosing in a multiple dose situation. Therefore, we developed a nanosuspension formulation of DCU to support oral, intravenous bolus and intravenous infusion dosing. Use of the nanosuspension formulation maintained DCU free plasma levels above the sEH IC50 and demonstrated that the application of formulation technology can accelerate in vivo evaluation of new targets by enabling pharmacodynamic studies of poorly soluble compounds.

Item Type:Article
Uncontrolled Keywords:nanosuspension; formulation; pharmacokinetics; efficacy; tool compounds
Subjects:Biomedical Science > Nanobiotechnology
ID Code:6143
Deposited By:IoN
Deposited On:21 Sep 2009 12:09
Last Modified:21 Sep 2009 12:09

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