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

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.