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: Investigation of utilization of nanosuspension formulation to enhance exposure of 1,3dicyclohexylurea in rats: Preparation for PK/PD study via subcutaneous route of nanosuspension drug delivery | Chiang et al. Nanoscale Research Letters 2011 6 413 http content 6 1 413 o Nanoscale Research Letters a SpringerOpen Journal NANO EXPRESS Open Access Investigation of utilization of nanosuspension formulation to enhance exposure of 1 3-dicyclohexylurea in rats Preparation for PK PD study via subcutaneous route of nanosuspension drug delivery Po-Chang Chiang Yingqing Ran Kang-Jye Chou Yong Cui and Harvey Wong Abstract 1 3-Dicyclohexylurea DCU a potent soluble epoxide hydrolase sEH inhibitor has been reported to lower systemic blood pressure in spontaneously hypertensive rats. One limitation of continual administration of DCU for in vivo studies is the compound s poor oral bioavailability. This phenomenon is mainly attributed to its poor dissolution rate and low aqueous solubility. Previously wet-milled DCU nanosuspension has been reported to enhance the bioavailability of DCU. However the prosperities and limitations of wet-milled nanosuspension have not been fully evaluated. Furthermore the oral pharmacokinetics of DCU in rodent are such that the use of DCU to understand PK PD relationships of sEH inhibitors in preclinical efficacy model is less than ideal. In this study the limitation of orally delivered DCU nanosuspension was assessed by a surface area sensitive absorption model and pharmacokinetic modeling. It was found that dosing DCU nanosuspension did not provide the desired plasma profile needed for PK PD investigation. Based on the model and in vivo data a subcutaneous route of delivery of nanosuspension of DCU was evaluated and demonstrated to be appropriate for future PK PD studies. Introduction In recent years researchers have demonstrated that various epoxyeicosatrienoic acid EETs regioisomers cause either vasodilatation or vasoconstriction in a number of vascular beds 1-3 and that they hold anti-inflammatory properties 4 . There is compelling evidence from the literature that increasing the levels of EETs demonstrates .
