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目的比较丹参酮IIA(TSN)脂微球与丹参酮IIA磺酸钠(STS)注射液iv给药后在大鼠体内的药动学行为及在小鼠组织中分布的差异。方法建立测定大鼠血浆和小鼠组织中TSN和STS的RP-HPLC方法。比较大鼠及小鼠分别单次iv TSN脂微球5.40 mg/kg和STS注射液7.27 mg/kg(均相当于18.35μmol/kg)后,TSN和STS在大鼠血浆中的水平和小鼠多个组织中的量,并对结果进行药动学拟合和统计学分析。结果 TSN脂微球在大鼠体内的生物利用度(AUC0～∞)、达峰浓度(Cmax)是STS注射液的2.14、2.22倍,清除率(CL)、表观分布容积(V)和滞留时间(MRT)也显著低于STS注射液(P<0.05、0.01),其他药动学参数均没有显著性差异;TSN和STS在小鼠组织中分布的检测结果表明,TSN在心、肝、脾、肺、肾组织中的AUC0～∞是等物质的量STS的1.94、0.11、0.98、1.65、0.28倍,且TSN在脑组织中的量显著增加,STS在脑组织中未检测到。结论等物质的量剂量下TSN与STS的药动学行为、组织分布具有显著差异,TSN脂微球比STS注射液生物利用度高、达峰浓度高,且显著靶向分布于心、脑、肺组织。
OBJECTIVE: To compare the pharmacokinetics of Tanshinone IIA (TSN) lipid microspheres with sodium tanshinone IIA sulfonate (STS) injection in rats and their distribution in mice. Methods RP-HPLC method for the determination of TSN and STS in rat plasma and mouse tissues was established. The levels of TSN and STS in rat plasma were compared with those of mice and mice treated with single iv TSN lipid microspheres 5.40 mg / kg and STS injection 7.27 mg / kg (both equal to 18.35 μmol / kg) The amounts in multiple tissues, and the results were pharmacokinetic fit and statistical analysis. Results The bioavailability of TSN lipid microspheres (AUC0 ~ ∞) in rats was 2.14, 2.22 times higher than that of STS injection, and the peak clearance (CL), apparent volume of distribution Time (MRT) was also significantly lower than STS injection (P <0.05,0.01), other pharmacokinetic parameters were not significantly different; TSN and STS distribution in mice tissue test results show that TSN in the heart, liver, spleen , AUC0 ~ ∞ in lung and kidney tissues were 1.94, 0.11, 0.98, 1.65 and 0.28 times of those of STS, and the amount of TSN in brain tissue increased significantly. STS was not detected in brain tissue. Conclusions TSN and STS have significant differences in pharmacokinetic behavior and tissue distribution under the dose of TSN. Microspheres of TSN have higher bioavailability and peak concentration than STS injection and are significantly targeted to the heart, brain, Lung tissue.