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  • Title: Enhanced absorption and tissue distribution of paclitaxel following oral administration of DHP 107, a novel mucoadhesive lipid dosage form.
    Author: Shin BS, Kim HJ, Hong SH, Lee JB, Hwang SW, Lee MH, Yoo SD.
    Journal: Cancer Chemother Pharmacol; 2009 Jun; 64(1):87-94. PubMed ID: 18941747.
    Abstract:
    PURPOSE: This study was conducted to examine the absorption and tissue distribution characteristics of paclitaxel-loaded DHP 107, a Cremophor EL-free, mucoadhesive lipid oral dosage form. METHODS: DHP 107 was orally administered to mice at 10, 20 and 40 mg/kg doses. For comparison purposes, Taxol was i.v. injected at 5, 10 and 20 mg/kg doses. Drug levels were determined in plasma and tissues by validated HPLC assays. The absolute bioavailability and the relative distribution to various tissues were calculated as a function of dose. RESULTS: The dose-normalized plasma AUC(DHP 107)/AUC(Taxol) ratios calculated at comparable AUC values ranged from 14.6 to 29.0%. In contrast, relative tissue distribution ratios calculated as the dose-normalized AUC(DHP 107)/AUC(Taxol) were as high as 342.0, 139.0, 112.9 and 108.2% for stomach, small intestine, large intestine and ovary, respectively. CONCLUSIONS: Oral administration of DHP 107 provided a substantial systemic absorption of paclitaxel. Furthermore, the relative distribution ratios of DHP 107 at doses of 20 and 40 mg/kg were higher for stomach, small intestine, large intestine, and ovary than the systemic bioavailability, providing a basis for therapeutic advantages.
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