中药新药前列栓给药途径选择的药动学依据

Explore the Role of the Administration Manner Based on Pharmacokinetics Evidence in New TCM Drug Discovery

采用RP HPLC法 ,比较研究前列栓经口和经肛门给药的药动学差异。结果表明 :(1 )经肛门途径用药 ,小檗碱在多数兔体内为一室开放模型 ,少数呈现为二房室模型 ,个别只能用统计矩拟合 ,其中一房室模型药代参数为t1 2 Ke=(96 2± 37 8)min ,cmax=(1 78 9± 88 9) μg·L-1 ,AUC =(4 791 7 4± 2 32 5 5 6 ) μg·L-1 ·min ;(2 )经灌胃途径给药 ,多数兔血药浓度在检测限以下 ,仅有 2只能测到完整曲线 ,可用一房室模型拟合 ,药代参数为t1 2 Ke=(5 73 4± 2 1 2 2 )min ,cmax=(7 0± 2 5 )μg·L-1 ,AUC =(772 5 2± 4 76 4 6 ) μg·L-1 ·min ,灌胃与肛塞相比的相对生物利用度仅为 2 6 0 7%和6 1 8% ;(3)前列腺组织药物浓度 ,经肛塞途径能测到部分 1～ 2h时间点的小檗碱浓度 ,但不足以构成可分析的浓度 时间曲线 ,而灌胃途径则根本无法测到小檗碱浓度 ,两组间差异极显著。经肛塞给药有以下优点 :吸收速度快、血药浓度高、血药有效浓度维持时间长、靶器官前列腺组织内药物浓度相对较高 ,且药动学参数随兔不同而有较大的差异。研究为前列栓的经肛门途径给药和栓剂剂型的确立 。

In order to explore the role of the route of administration based on pharmacokinetics evidence in new TCM drug Qianlieshuan (QLS) discovery. The authors use the methods as follow: the main component berberine containing in QLS in serum was detected by RP HPLC with UV detector, and the pharmacokinetics apparent parameters were compared between oral and rectal administration and were calculated by the 3P97 Pharmacokinetics Software.The results were: (1) In rectal administration, the models of pharmacokinetics of berberine were one compartment open model in most rabbits, two compartments model in few rabbits, exceptional one can only fitted with statistics moment. One compartment model parameters: t 1/2 K e =(96 2±37 8)?min, c max =(178 9±88 9)?μg·L -1 , AUC=(47?917 4±23?255 6)?μg·L -1 ·min. (2) In oral administration, the plasma concentrations of berberine in most of the rabbits were under the detectability, only in two rabbits were detected and composed entire concentration time curves and could be fitted with one compartment model, the parameters were as follow: t 1/2 K e =(573 4±212 2)?min, c max =(7 0±2 5)?μg·L -1 , AUC=(7?725 2±4?764 6)?μg·L -1 ·min. The relative bioavailability of powder form by oral administration when compared with suppository by rectal administration was only 26 07% and 6.18%, respectively. (3) Prostatic tissue concentration of berberine could be detected in 1 2?h administered by rectal in some rabbits, but couldn't be detected when given by oral. There was significant difference between the two groups. Above mentioned results were shown that: (1) More advantages by rectal administration than administration by oral: rapid absorption, higher plasma concentration, longer efficient plasma concentration steady state, higher concentration of berberine in target organ which is prostate.(2) The pharmacokinetics evidence to establish the rectal administration and certain suppository for QLS.