双黄连粉针不同剂量给药后黄芩苷的药动学及唾液中的分布

Pharmacokinetics and Salivary Distribution of Baicalin in Shuanghuanglian at Different Doses Administration

目的明确双黄连粉针剂不同剂量给药后有效成分黄芩苷在大鼠体内的动态变化规律及其在唾液中的分布情况。方法大鼠静脉注射双黄连粉针后，反相高效液相色谱法测定黄芩苷的血液、唾液浓度，采用药动学软件MULT197V10程序进行数据处理，确定药动学参数。结果双黄连粉针剂高、中、低剂量（740，555，370mg·kg^-1）给药后有效成分黄芩苷在大鼠体内符合二室模型分布，其高、中、低剂量主要药动学参数分别如下：t1／2=（0．79±0．12）h，AUC=（1．30±0．13）mg·h·mL^-1，Vc=（0．21±0．036）L，CL=（0．19±0．019）L·h^-1；t1／2=1．52±0．14h，AUC=（1．22±0．20）mg·h·mL^-1，K=（0．36±0．04）L，CL=（0．16±0．030）L·h^-1。；t1／2=（0．34±0．021）h，AUC=（0．22±0．004）mg·h·mL^-1，K=（0．33±0．027）L，CL=（0．66±0．014）L·h^-1。高剂量给药后黄芩苷唾液浓度范围为：0．11～0．78μg·mL^-1，中、低剂量给药后唾液样品中未检测到黄芩苷。结论通过高、中、低剂量及相应的AUC对比，AUC随剂量增加不成比例增加，说明双黄连粉针给药后黄芩苷在体内呈非线性药动学消除过程。另外，黄芩苷向唾液中分布的浓度较血液低的多。

OBJECTIVE To identify pharmacokinetics and salivary distribution of baicalin after different doses administration of Shuanghuanglian injection to rats. METHODS Each rat was given a dose of Shuanghuanglian injection via the vein. An RP-HPLC method was used to determine the concentrations of baicalin in plasma and saliva. Pharmacokinetic model and parameters were analyzed by pharmacokinetics program MULTI97V10. RESULTS Baicalin showed two compartment model after administration of Shuanghuanglian at high, medium and low-dose （740,555,370 mg·kg^-l） and the main parameters of pharmacokinetics in each dose were as follows ：tl/2 = （0.79 ±0.12 ） h, AUC = （ 1.30 ± 0.13 ）mg · b ·mL^-1 , Vc = （0.21 ± 0.036） L, CL = （ 0.19 ± 0.019 ） L · h^-1 ; t1/2=（1.52±0.14）h, AUC=（1.22±0.20）mg·h· mL^-1,V1： =（0.36±0.04）L,CL=（0.16±0.030）L · h^-1;t1/2 = （0.34± 0. 021 ） h, AUC = （0.22 ± 0. 004） mg ·h · mL^-1 , V, = （0.33 ± 0.027 ） L, CL = （0.66 ± 0. 014） L · h^-l. The salivary level of baicalin in high-dose was within 0.11-0.78 μg ·mL^-1. CONCLUSION Because AUC of baicalin was not increased proportionally with the doses of Shuanghuanglian,it was suggested that baicalin would present nonlinear pharmacokinetics. Baiealin was excreted into saliva much more lowly than blood.