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
<p>Abstract</p> <p>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 <it>in vivo </it>studies is the...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
SpringerOpen
2011-01-01
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| Series: | Nanoscale Research Letters |
| Online Access: | http://www.nanoscalereslett.com/content/6/1/413 |
| Summary: | <p>Abstract</p> <p>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 <it>in vivo </it>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 <it>in vivo </it>data, a subcutaneous route of delivery of nanosuspension of DCU was evaluated and demonstrated to be appropriate for future PK/PD studies.</p> |
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| ISSN: | 1931-7573 1556-276X |