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01-05-2013 | Original Article

Pharmacokinetics and tissue distribution of larotaxel in rats: comparison of larotaxel-loaded microsphere with larotaxel-solution

Authors: Zhenzhen Liu, Yukun Feng, Lunhui Zhang, Guofei Li, Lulu Geng, Yan Cui, Fei Teng, Xing Tang, Kaishun Bi, Xiaohui Chen

Published in: Cancer Chemotherapy and Pharmacology | Issue 5/2013

Abstract

Purpose

Larotaxel is a new taxane compound with poor solubility. The aim of this study is to develop a new formulation to locate the poorly soluble drug and compare the pharmacokinetics and tissue distribution of larotaxel-loaded microsphere (LTX-LM) with the solution form larotaxel-solution (LTX-solution).

Methods

A sensitive and efficient UPLC-MS/MS method was developed and validated for determination of larotaxel in rat plasma and tissues and applied to assess the plasma protein binding, pharmacokinetics, and tissue distribution.

Results

Pharmacokinetic study indicated that larotaxel plasma disposition was triphasic, and LTX-LM group had markedly higher AUC, smaller clearance, and lower apparent volume of distribution than the LTX-solution group. The tissue distribution exhibited significant lower uptake of LTX-LM in lung, kidney, heart, muscle, and brain among all the tissues, indicating the advantage of LTX-LM over the solution form in reducing drug precipitation in vivo and toxicity in cardiovascular system and central nervous system.

Conclusions

These results suggest that lipid microsphere could be an effective parenteral carrier for LTX delivery in cancer treatment.

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Title: Pharmacokinetics and tissue distribution of larotaxel in rats: comparison of larotaxel-loaded microsphere with larotaxel-solution
Authors: Zhenzhen Liu
Yukun Feng
Lunhui Zhang
Guofei Li
Lulu Geng
Yan Cui
Fei Teng
Xing Tang
Kaishun Bi
Xiaohui Chen
Publication date: 01-05-2013
Publisher: Springer-Verlag
Published in: Cancer Chemotherapy and Pharmacology / Issue 5/2013
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-013-2104-2

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Abstract

Purpose

Methods

Results

Conclusions

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