Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành hóa học dành cho các bạn yêu hóa học tham khảo đề tài: Pharmacokinetic evaluation of a 1,3-dicyclohexylurea nanosuspension formulation to support early efficacy assessment | Nanoscale Res Lett 2007 2 291-296 DOI S11671-007-9063-7 NANO EXPRESS Pharmacokinetic evaluation of a 1 3-dicyclohexylurea nanosuspension formulation to support early efficacy assessment Jan L. Wahlstrom Po-Chang Chiang Sarbani Ghosh Chad J. Warren Steve P. Wene Lesley A. Albin Mark E. Smith Steven L. Roberds Received 29 January 2007 Accepted 9 May 2007 Published online to the authors 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 This study was supported by Pharmacokinetics Dynamics and Metabolism at Pfizer. J. L. Wahlstrom H C. J. Warren S. P. Wene L. A. Albin M. E. Smith Pharmacokinetics Dynamics and Metabolism Pfizer Global Research Development St. Louis Laboratories Pfizer Inc. 700 Chesterfield Parkway West T312E Chesterfield MO 63017 USA e-mail janw@ . Chiang Pharmaceutical Sciences Pfizer Global Research Development St. Louis Laboratories Pfizer Inc. St Louis MO USA S. Ghosh S. L. Roberds Molecular Pharmacology Pfizer Global Research Development St. Louis Laboratories Pfizer Inc. St Louis MO USA 12 June 2007 application of formulation technology can accelerate in
