丹参酮Ⅱ_A脂微球与丹参酮Ⅱ_A磺酸钠注射液的药动学与组织分布比较研究

Comparison on pharmacokinetics and tissue distribution of tanshinone IIAlipid microsphere and sodium tanshinone IIAsilate injection

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 in rats and tissue distribution in mice of tansbinone IIA （TNS） lipid microsphere and sodium tanshinone IIA silate （STS） injection after iv injection. Methods A sensitive and specific RP-HPLC method was established to determine the concentration of TSN and STS in rat plasma and mice tissue. The TSN and STS levels in plasma of rats and tissues of mice were compared after iv single dose administration of TSN lipid microsphere （5.40 mg/kg） and STS injection （7.27 mg/kg）, and the results were fitted by pharmacokinetic and statistic analyses. Results The bioavailability （AUC0-∞） and peak concentration （Cmax） values of TSN were 2.14 and 2.22 folds as those of STS, the clearance （CL）, apparent volume of distribution （V）, and mean repair time （MRT） values of TSN were lower （P 〈 0.01）, and other pharmacokinetie parameters had no significant deviation. The results on the tissue distribution of TSN and STS in mice showed that the contents of TSN in heart, liver, spleen, lung, and kidney tissues were 1.94, 0.11, 0.98, 1.65, and 0.28 folds as those of STS with the same molar dose, and the content of TSN in brain tissue increased more significantly than that of STS which has not been detected. Conclusion The pharmacokinetics and tissue distribution of TSN and STS at the same molar dose have significant differences, the AUC and Cmax values of TSN are higher, and the concentration of TSN could be increased in heart, brain, and lung tissues significantly, compared with those of STS.