Abstract: AIM: To determine amphotericin B concentrations in plasma and tissues and to compare the pharmacokinetic profile in dogs and distribution profile in SD rats main tissues of test and reference amphotericin B liposome. METHODS: Six dogs were intravenously administered of 5 mg/kg test and reference preparations in an randomized cross-over study. Blood samples were collected at various time-points after drug administration. Rats were intravenously administered of 5 mg/kg test and reference preparations, tissues were collected at various time-points after drug administration. Analytical method based on HPLC method was established to determine the plasma and tissue concentration. The pharmacokinetic evaluation was carried out using the DAS 2.0 program. RESULTS: Six dogs were intravenously administered of 5 mg/kg amphotericin B liposome, and an open two compartment model best described the concentration-time profiles for amphotericin B liposome. The main pharmacokinetic parameters were t_1/2β(53.6±2.2)h, AUC(18.7±3.2)mg·L^-1·h ; CL(0.23±0.05) L·h^-1 ·kg^-1, V₁ (11.6±2.8) L/kg for the test preparation and t_1/2β(52.8±0.9)h, AUC(19.6±2.2)mg·L^-1·h, CL (0.22±0.03) L·h^-1 ·kg^-1, V₁(10.6±2.9)L/kg for the reference preparation. CONCLUSION: The statistics analysis shows that there are no significant differences(P > 0.05)between the test and reference preparation in major pharmacokinetic parameters in dogs and tissue distribution in rats.

Key words: amphotericin B, liposome, HPLC, pharmacokinetics