SpringerOpen Newsletter

Receive periodic news and updates relating to SpringerOpen.

Open Access Nano Express

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

Jan L Wahlstrom1*, Po-Chang Chiang2, Sarbani Ghosh3, Chad J Warren1, Steve P Wene1, Lesley A Albin1, Mark E Smith1 and Steven L Roberds3

Author Affiliations

1 Pharmacokinetics, Dynamics and Metabolism, Pfizer Global Research & Development, St. Louis Laboratories, Pfizer Inc., 700 Chesterfield Parkway West, T312E, Chesterfield, MO, 63017, USA

2 Pharmaceutical Sciences, Pfizer Global Research & Development, St. Louis Laboratories, Pfizer Inc., St Louis, MO, USA

3 Molecular Pharmacology, Pfizer Global Research & Development, St. Louis Laboratories, Pfizer Inc., St Louis, MO, USA

For all author emails, please log on.

Nanoscale Research Letters 2007, 2:291-296  doi:10.1007/s11671-007-9063-7

Published: 12 June 2007

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.

Keywords:
Nanosuspension; Formulation; Pharmacokinetics; Efficacy; Tool compounds