Pharmacokinetics and tissue distribution of mitomycin amphiphilic chitosan polymeric micelles in rats / 中国药学杂志

ABSTRACT

OBJECTIVE: To investigate the pharmacokinetics and tissue distribution of mitomycin amphiphilic chitosan polymeric micelles (MMC-ACPM) in rats. METHODS: Mitomycin injection (MMC-INJ) and MMC-ACPM were administered to rats through tail vein at the dosage of 0. 5 mg · kg-1. An ultra-fast liquid chromatography with tandem mass spectrometry (UPLC-MS/MS) method was established to determine the concentration of mitomycin (MMC) in plasma and tissues of rats. RESULTS: The t1/2(β) of MMC-INJ and MMC-ACPM in plasma were estimated to be (0.67 ± 0.36) and (3.33 ± 1.47) h, respectively. The AUC0→∞ were calculated to be (120.94 ± 13.77) and (140.95 ± 11.56) ng · mL-1 · h-1, respectively. The MRT were (0.83 ±0.13) and (1.56 ± 0.22) h, and CL were (0.005 ± 0.001) and (0.003 ± 0.001) L · h-1 · kg-1, respectively. Compared with MMC-INJ group, MMC-ACPM group had lower concentrations of MMC in heart, liver, spleen, lung, and kidney of rats. CONCLUSION: MMC-ACPM can prolong the circulation of MMC in vivo, improve its bioavailability, and reduce the accumulation in liver and kidney, which can improve curative effects and reduce toxicity.