Metabolic profile of lung-targeted docetaxel liposomes in rabbits, rats and mice

Abstract

1. Docetaxel (DTX) liposome powder was stable over three months, and the liposome suspension was stable within 8 h.2. Rabbits, rats and mice were intravenously treated with DTX-LP or with a DTX injection (DTX-IN). Four major metabolites of DTX were identified in feces: M1, M2, M3 and M4. However, M4 was not found in the bile.3. The most abundant metabolite in the feces was M2 followed by M1/M3, with only a small amount of M4 observed. The most abundant metabolite in bile was also M2, followed by M1/M3.4. The liposomal delivery of DTX did not alter the in vivo drug metabolism, and there were no significant differences among the three species tested. This suggested that this formulation is pharmaceutically safe for clinical use. In contrast to the traditional injected formula, DTX-LP administration significantly delayed drug metabolism, as observed in feces and bile. This property will greatly enhance the DTX therapeutic efficacy and reduce the systemic side effects of NSCLC treatment.