Planta Med 2010; 76(14): 1592-1595
DOI: 10.1055/s-0030-1249836
Pharmacology
Original Papers
© Georg Thieme Verlag KG Stuttgart · New York

Transport of a Hydrophilic Paclitaxel Derivative, 7-Xylosyl-10-Deacetylpaclitaxel, by Human Intestinal Epithelial Caco-2 Cells

Shougang Jiang1 , 2 , Yuangang Zu1 , 2 , Yu Zhang1 , 2 , Yujie Fu1 , 2 , Zhuo Wang1 , 2 , Jingtao Wang1 , 3
  • 1Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University, Harbin, P. R. China
  • 2Engineering Research Center of Forest Bio-preparation, Ministry of Education, Northeast Forestry University, Harbin, P. R. China
  • 3College of Pharmacy, Jiamusi University, Jiamusi, P. R. China
Further Information

Publication History

received Dec. 15, 2009 revised March 18, 2010

accepted March 23, 2010

Publication Date:
22 April 2010 (online)

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Abstract

7-Xylosyl-10-deacetylpaclitaxel is an active compound used in traditional Chinese medicine to treat cancer. However, pharmacokinetic studies yielded low plasma concentrations of 7-xylosyl-10-deacetylpaclitaxel after its oral administration in preclinical trials. Therefore, we investigated whether the observed low oral bioavailability of this compound is due to poor absorption. We studied the transepithelial flux of 7-xylosyl-10-deacetylpaclitaxel using the human colonic cell line Caco-2 as a model and found out that its flux (at a concentration range of 0.5–20 µM) across the Caco-2 cell layer was linear with time for up to 3 hr. The apparent maximal concentration (KM) of the active efflux component was 93.4 µM. Verapamil (50 µM) and tetrandrine (25 µM) significantly decreased the active transport component. These data support the conclusion that rapid passive diffusion of 7-xylosyl-10-deacetylpaclitaxel through the intestinal epithelium is partially counteracted by the action of an outwardly directed efflux pump, presumably P-glycoprotein. The relatively high apparent permeability coefficient (P app) for the apical to basolateral 7-xylosyl-10-deacetylpaclitaxel transport (16.3 ± 6.3 × 10−6 cm/s; n = 3) suggests that the drug may still be effectively absorbed in the intestinal tract.

References

Dr. Yuangang Zu

Key Laboratory of Forest Plant Ecology
Northeast Forestry University

No. 26, Hexing Street

150040 Harbin

People's Republic of China

Phone: + 86 4 51 82 19 15 17

Fax: + 86 4 51 82 10 20 82

Email: cpu127@126.com