Influences of formulations and administration routes on docetaxel tissue distribution in mice

Docetaxel (DTX) is an antimicrotubular chemotherapy drug widely used for treating various cancers. The objective of this study was to evaluate the impact of formulations and administration routes on DTX tissue distribution. The pharmacokinetics and tissue distribution of DTX were assessed using intravenous (IV) injection, intraperitoneal (IP) injection, oral solution, and oral granules in male CD-1 mice. Despite containing DTX crystals, oral DTX granules achieved tissue exposure comparable to that of the oral DTX solution, effectively addressing the poor solubility challenge of DTX while highlighting the need for strategies to enhance permeability in oral DTX formulations. Tissue distribution analysis revealed rapid elimination of DTX from the bloodstream and rapid uptake of DTX into tissue, regardless of formulation or route, emphasizing the importance of tissue concentrations over blood concentrations in evaluating therapeutic efficacy and toxicity for DTX. Notably, DTX exhibited lung selectivity, with oral formulations showing greater lung targeting compared to IP injection. These findings deepen the understanding of DTX tissue distribution and provide critical insights for DTX-based chemotherapy, as well as the development and optimization of novel DTX formulations, particularly for advancing oral DTX treatments and improving cancer therapy.