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

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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.

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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

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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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Authors and Affiliations

  1. Department of Pharmaceutics, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, 110016, Liaoning Province, People’s Republic of China

    Mingming Zhao, Min Su, Xia Lin, Yanfei Luo, Haibing He, Cuifang Cai & Xing Tang

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  1. Mingming Zhao
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  2. Min Su
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  3. Xia Lin
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  7. Xing Tang
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Correspondence to Xing Tang.

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Zhao, M., Su, M., Lin, X. et al. Evaluation of Docetaxel-Loaded Intravenous Lipid Emulsion: Pharmacokinetics, Tissue Distribution, Antitumor Activity, Safety and Toxicity. Pharm Res 27, 1687–1702 (2010). https://doi.org/10.1007/s11095-010-0180-0

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  • DOI: https://doi.org/10.1007/s11095-010-0180-0

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