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Pharmaceutical Research

, Volume 27, Issue 8, pp 1687–1702 | Cite as

Evaluation of Docetaxel-Loaded Intravenous Lipid Emulsion: Pharmacokinetics, Tissue Distribution, Antitumor Activity, Safety and Toxicity

  • Mingming Zhao
  • Min Su
  • Xia Lin
  • Yanfei Luo
  • Haibing He
  • Cuifang Cai
  • Xing Tang
Research Paper

ABSTRACT

Purpose

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.

Methods

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).

Results

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.

Conclusions

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 WORDS

docetaxel evaluation lipid emulsion 

ABBREVIATIONS

A549

the A549 human pulmonary adenocarcinoma cell line

ALB

albumin

ALP

alkaline phosphatase

ALT

alanine transaminase

AST

aspartate transaminase

BCAP-37

the BCAP-37 human breast cancer cell line

BEL7402

the BEL7402 human hepatocellular carcinoma cell line

BUN

blood urea nitrogen

CK

creatinine kinase

Cr

creatinine

CT

coagulation time

DC

WBC differential count

DLE

lipid emulsion for docetaxel

DS

Taxotere

DTX

docetaxel

GCT

gama glutamyl transferase

GLB

globulin

GLU

glucose

HB

hemoglobin

HCT

hematocrit

MCHC

mean corpuscular hemoglobin concentration

MCV

mean corpuscular volume

PLT

blood platelet count

RBC

the red blood cell count

Ret

reticulocyte count

RTV

the relative tumor volume

T/C

the percentage of tumor growth rate

TBIL

total bilirubin

TBME

tert-butyl methyl ether

TCHO

total cholesterol

TG

triglyceride

TGI

the percentage of tumor growth inhibition rate

TP

total protein

U-BIL

bilirubin in urine

URO

urobilinogen in urine

WBC

white blood cell count

Notes

ACKNOWLEDGEMENTS

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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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Mingming Zhao
    • 1
  • Min Su
    • 1
  • Xia Lin
    • 1
  • Yanfei Luo
    • 1
  • Haibing He
    • 1
  • Cuifang Cai
    • 1
  • Xing Tang
    • 1
  1. 1.Department of PharmaceuticsShenyang Pharmaceutical UniversityShenyangPeople’s Republic of China

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