Effects of lipid vehicle and P-glycoprotein inhibition on the mesenteric lymphatic transport of paclitaxel in unconscious, lymph duct-cannulated rats
| Autor: | Xinxian Deng, Teng Shen, Mingkang Zhong, Dianyun An, Qingqing Cai, Zhongdong Li |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Male
Paclitaxel Linoleic acid Pharmaceutical Science Biological Availability 02 engineering and technology Pharmacology 030226 pharmacology & pharmacy Intestinal absorption Catheterization Excipients Linoleic Acid Lymphatic System Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Pharmacokinetics medicine Animals Mesentery ATP Binding Cassette Transporter Subfamily B Member 1 Intestinal Mucosa P-glycoprotein biology business.industry General Medicine 021001 nanoscience & nanotechnology Calcium Channel Blockers Antineoplastic Agents Phytogenic Lipids Bioavailability Rats Lymphatic system chemistry Verapamil biology.protein Lymph 0210 nano-technology business medicine.drug |
| Zdroj: | Drug delivery. 23(1) |
| ISSN: | 1521-0464 |
| Popis: | The present study examined the effects of lipid vehicle and intestinally based efflux processes on intestinal lymphatic transport of paclitaxel (PTX) in the mesenteric lymph duct-cannulated anesthetized rat model. PTX solution alone, PTX solution pretreated with the P-glycoprotein (P-gp) inhibitor verapamil and/or PTX and a 2:1 (w/w) mixture of linoleic acid:glycerol monooleate were administered intraduodenally to anesthetized rats. Coadministration of a mixture of linoleic acid-monoolein significantly increased the extent of intestinal lymphatic transport of PTX, but it had little impact on the absolute oral bioavailability of PTX. In contrast, pretreatment with verapamil increased both the extent of lymphatic transport (3.5-fold) and absolute oral bioavailability (1.8-fold). Further increase in the lymphatic transport (6.5-fold) and absolute oral bioavailability (1.8-fold) was achieved by the combination of pretreatment with verapamil and coadministration with the linoleic acid-monoolein mixture. These data indicate that the application of lipid vehicle holds promise for selectively targeted lymphatic delivery of PTX. P-gp inhibition can result in both increased intestinal lymphatic levels and absolute oral bioavailability of PTX. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|