title: Pharmacokinetic synergy from the taxane extract of Taxus chinensis improves the bioavailability of paclitaxel.
abstract: BACKGROUND
  Taxus chinensis (Pilger) Rehd is widely distributed in China and the northern hemisphere, and the most popular medicinal component isolated from Taxus chinensis is paclitaxel (PTX), which has now become the first-line chemotherapeutic drug for breast cancer and ovarian cancer. Oral administration of pure PTX as a potential anti-cancer agent is compromised by low bioavailability.
  
  
  OBJECTIVE
  In the clinical practice of traditional Chinese medicine, drug co-administration in the form of mixtures or formula could achieve pharmacokinetic/pharmacodynamic synergies. In this study, we aimed to investigate whether there exist any 'inherent' phytochemical synergy from Taxus chinensis extract that could improve PTX bioavailability.
  
  
  METHODS
  Pharmacokinetic study of PTX after oral administration of Taxus chinensis extracts or single PTX was performed. In addition, comparative cytotoxic studies were carried out on the MCF-7 breast cancer cell lines.
  
  
  METHODS
  The plasma concentrations of PTX were determined using a validated high performance chromatography tandem mass spectrometry method. The cytotoxicity was compared using the MTT assay.
  
  
  RESULTS
  Oral administration of taxane fractions isolated from Taxus chinensis (containing 17.2% PTX) could achieve remarkably higher blood concentration and systemic exposure of PTX in rats, while the retention of PTX was significantly improved. Further tissue distribution analysis revealed that the penetration of PTX into major tissues was drastically increased compared with that of single PTX. In addition, in MCF-7 cells, the co-existing components in taxane mixtures could strengthen the inhibitory effects of PTX on tumor cell proliferation.
  
  
  CONCLUSIONS
  Together, these results support that administration of PTX in the form of taxane mixtures may become a novel approach to improve the poor bioavailability of PTX. Moreover, the inherent synergy from Taxus chinensis taxane extracts promises a novel strategy to strengthen PTX efficacy.
authors.affiliation: Department of Pharmacy, Nanjing University of Chinese Medicine Affiliated Hospital, 155 HanZhong Road, Nanjing 210029, China. Electronic address: liuzh1008@126.com.
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Pharmacy, Nanjing University of Chinese Medicine Affiliated Hospital, 155 HanZhong Road, Nanjing 210029, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Zheng
authors.affiliation: School of Pharmaceutical Sciences, Zunyi Medical University, Zunyi 563003, China.
authors.forename: Jiajia
authors.initials: J
authors.lastname: Lv
authors.affiliation: Department of Pharmacy, Nanjing University of Chinese Medicine Affiliated Hospital, 155 HanZhong Road, Nanjing 210029, China.
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Pharmacy, Nanjing University of Chinese Medicine Affiliated Hospital, 155 HanZhong Road, Nanjing 210029, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, Nanjing University of Chinese Medicine Affiliated Hospital, 155 HanZhong Road, Nanjing 210029, China.
authors.forename: Xiaozhou
authors.initials: X
authors.lastname: Wen
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Liu
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Jingyi
authors.initials: J
authors.lastname: Jiang
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Liling
authors.initials: L
authors.lastname: Wang
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000097:blood / Q000493:pharmacokinetics*; D001682:Biological Availability; D001952:Bridged-Ring Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004357:Drug Synergism; D006801:Humans; D061986:MCF-7 Cells; D008297:Male; D008813:Mice, Inbred ICR; D015394:Molecular Structure; D017239:Paclitaxel / Q000097:blood / Q000493:pharmacokinetics*; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D043823:Taxoids / Q000008:administration & dosage / Q000493:pharmacokinetics*; D020946:Taxus / Q000737:chemistry*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D001952:Bridged-Ring Compounds; D010936:Plant Extracts; D043823:Taxoids; C080625:taxane; D017239:Paclitaxel
keywords: Bioavailability; Cytotoxicity; Paclitaxel; Pharmacokinetic synergy; Taxus chinensis var. mairei; Tissue distribution