Department of Pharmaceutics, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, 110016, Liaoning Province, People's Republic of China.
Pharm Res. 2010 Aug;27(8):1687-702. doi: 10.1007/s11095-010-0180-0. Epub 2010 Jun 15.
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(R) (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.
本研究旨在对一种不含 Tween 80 的多西他赛静脉用脂肪乳剂（DLE）进行详细的临床前评价。
系统考察了 DLE 在大鼠和比格犬体内的药代动力学、组织分布、抗肿瘤活性、安全性试验和毒性，与 Taxotere（R）（DS）进行了比较。
大鼠的药代动力学研究表明，DLE 与 DS 相比具有更高的血浆浓度和 AUC，AUC 与剂量之间存在良好的相关性，而在比格犬中，DLE 与 DS 具有生物等效性。组织分布研究表明，两种制剂的分布特征相似，表明 DLE 不会改变多西他赛在体内的分布。此外，DLE 在安全性研究中与 DS 一样安全，并在裸鼠中对 A549、BEL7402 和 BCAP-37 细胞系显示出与 DS 相似的显著抗肿瘤活性。长期毒性研究的相应结果表明，DLE 比 DS 毒性更小，且毒性作用可逆转。
本文研究的 DLE 被发现是一种有吸引力的新制剂，是多西他赛临床应用的合适选择。
