| Title | Improvement of cyclosporine A bioavailability by incorporating ethyl docosahexaenoate in the microemulsion as an oil excipient. | | Author(s) | Hirunpanich V, Sato H | | Institution | Department of Clinical and Molecular Pharmacokinetics/Pharmacodynamics, School of Pharmacy, Showa University, Shinagawa-ku, Tokyo, 142-8555, Japan. | | Source | Eur J Pharm Biopharm 2009 Jun 25. | | Abstract | The aims of this study were to determine the effect of ethyl docosahexaenoate (DHA-EE) on cyclosporine A (CsA) bioavailability, while also examining the effect of DHA-EE on CsA when DHA-EE was incorporated into a microemulsion formulation as an oil ingredient. The oral co-administration of DHA-EE and CsA increased the blood CsA concentration in a dose-dependent manner, and the AUC and C(max) both increased by about 2-fold with 100 mg/kg DHA-EE. The microemulsion formulation of CsA consisted of Tween-20, ethanol, water and DHA-EE (53.3/6.5/35.9/3.3% w/w) (namely DHA-ME) was transparent and stable with an average particle size of 50 nm which was similar to that of the control formulation incorporating vitamin E instead of DHA-EE (namely VE-ME). The permeabilities of CsA from DHA-ME, VE-ME and Neoral((R)) formulations across an artificial membrane were not significantly different. The C(max) and AUC(0-infinity) of CsA in rats administered DHA-ME significantly increased by approximately 2-fold in comparison to that of VE-ME. The relative oral bioavailability (F(r)) of DHA-ME in comparison to Neoral((R)) was determined to be 114% while the F(r) of VE-ME was only 60%. It was therefore suggested that the use of DHA-EE as an oil excipient may be promising for the development of a microemulsion formulation of CsA with an improved oral bioavailability. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19560537 |
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