Evaluation of Docetaxel-Loaded Intravenous Lipid Emulsion: Pharmacokinetics, Tissue Distribution, Antitumor Activity, Safety and Toxicity
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The purpose of this study was to carry out a detailed evaluation of an intravenous lipid emulsion for docetaxel (DLE) without Tween 80 before clinical administration.
The pharmacokinetics in rats and beagle dogs, tissue distribution, antitumor activity, safety test and toxicity of DLE have been investigated systematically to evaluate the formulation and compared with Taxotere® (DS).
The pharmacokinetic study in rats revealed that DLE exhibited higher plasma concentrations and AUC than DS, and a good correlation was observed between AUC and dose, while, in beagle dogs, the DLE was bioequivalent to DS. The tissue distribution study showed that the profiles of the two formulations were similar, indicating the DLE did not change the distribution of docetaxel in vivo. Furthermore, DLE was as safe as DS in the safety investigation and displayed significant antitumor activities against the A549, BEL7402 and BCAP-37 cell lines in nude mice, similar to DS. The corresponding results of the long-term toxic study demonstrated the DLE was less toxic than DS, and the toxic effects could be reversed.
The DLE investigated in this paper was found to be an attractive new formulation and an appropriate choice for the clinical administration of docetaxel.
KEY WORDSdocetaxel evaluation lipid emulsion
the A549 human pulmonary adenocarcinoma cell line
the BCAP-37 human breast cancer cell line
the BEL7402 human hepatocellular carcinoma cell line
blood urea nitrogen
WBC differential count
lipid emulsion for docetaxel
gama glutamyl transferase
mean corpuscular hemoglobin concentration
mean corpuscular volume
blood platelet count
the red blood cell count
the relative tumor volume
the percentage of tumor growth rate
tert-butyl methyl ether
the percentage of tumor growth inhibition rate
bilirubin in urine
urobilinogen in urine
white blood cell count
Professor Hui Zheng from Department of Pharmacology, China National Institute for Radiological Protection is kindly acknowledged for his assistance in the antitumor activity, safety test and long-term toxicity. Dr. David B Jack is gratefully thanked for correcting English of the manuscript.
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