【作者】 杨炳华；

【导师】 钟大放；

【作者基本信息】 沈阳药科大学 ， 药物分析学， 2004， 博士

【摘要】 自20世纪70年代以来，有关野黄芩苷（scutellarin，其结构式见图Fig．a）的药理作用及临床应用方面的报道很多，而有关其体内情况的研究报道却很少。本论文实验的研究目的主要是对野黄芩苷在体内的药物动力学及代谢进行探讨，分别考察了野黄芩苷在大鼠、Beagle犬及人体内的吸收动力学，比较其种属差异，其中在大鼠及人体内的吸收动力学研究为首次报道。建立HPLC-UV法考察了野黄芩苷在大鼠体内的组织分布情况，表明野黄芩苷及其代谢产物野黄芩素在大鼠体内分布广泛。应用HPLC，LC／MSⁿ等方法从大鼠尿样及胆汁中发现了野黄芩苷的10种代谢物，其中有5种代谢物为首次报道；成功应用LC-MSⁿ法分离鉴定了3对互为同分异构体的代谢产物。研究了野黄芩苷对大鼠肝微粒体P450酶的影响。初步阐明了野黄芩苷在体内的吸收，分布及代谢过程，为指导新药开发和临床用药提供了一定的理论依据。 一、野黄芩苷在大鼠体内的吸收动力学研究 建立了HPLC-UV法测定大鼠血浆中的野黄芩苷，色谱柱为C₁₈柱，流动相为50mmol／l磷酸二氢铵缓冲液-甲醇-乙腈（63：22：15，v／v／v，pH 2.5），紫外检测波长为335nm，线性范围为0.050-12.5μg／ml，最低定量浓度为0.050μg／ml。更多还原

【Abstract】 There were few reports on pharmacokinetics and metabolism of scutellarin, although whose pharmacodynamics and clinic application have been studied from the 1970’s in China. Pharmacokinetics and metabolism of scutellarin were studied in this dissertation, including absorption pharmacokinetics, tissue distribution and metabolism in rats, absorption pharmacokinetics in Beagle dogs, and its bioavailability in healthy volunteers. The effect of scutellarin on P450 enzymes in rat liver microsomes was evaluated for the first time. These studies provided scientific data for the new drug development and clinic use.1. Absorption pharmacokinetics in ratsTo investigate the absorption pharmacokinetics of scutellarin in rats, a novel HPLC-UV method was firstly established to determine scutellarin in rat plasma. Chromatographic separation was achieved on a Diamonsil C18 column. The mobile phase consisted of methanol-acetonitrile-50 mmol/l NH₄H₂PO₄ buffer （22:15:63, v/v/v, adjusted to pH 2.5 with 1 mol/l phosphoric acid） at a flow-rate of 1.0 ml/min. The ultraviolet detector operated at 335 nm. Linear calibration curves were obtained over the concentration range of 0.050-12.5 μg/ml for scutellarin in rat plasma. The lower limit of quantitation （LLOQ） was 0.050 μg/ml.Individual plasma-concentration data were analyzed by non-compartmental and compartmental analysis, after iv or ig administration of scutellarin at the dose of 40 mg/kg to rats. Mean plasma concentration-time curves of scutellarin were best fitted to three-compartmental models. The absolute oral bioavailability of scutellarin in rats was 4.98%.更多还原