摘要
目的 研究马兜铃酸A在正常大鼠体内的药动学。方法 建立了测定马兜铃酸A的高效液相色谱法。色谱条件为HYPERSIL C18柱 (5 μm ,4 0mm× 2 0 0mm) ,流动相为甲醇 :四氢呋喃 :0 .0 2 5mol/LKH2 PO4(pH =3.8) (4 4 :6 :5 0 ) ,流速为 1mL/min ,检测波长为 315nm。SD大鼠 8只 ,分成 2组 ,分别静脉注射马兜铃酸A溶液 0 .2 5mg/kg、2 .5mg/kg ,测定不同时间的血药浓度。用 3p97药动学程序对血药浓度 时间数据进行拟合。结果 大鼠静注马兜铃酸A后 ,其主要的药动学参数为 :低剂量组VC(0 .0 13± 0 .0 0 4 )L ,CLs(0 .2 0 6±0 .132 )L/h ,T1/ 2α(2 .5± 0 .8)min ,T1/ 2 β(10 .9± 2 .5 )min ,曲线下面积AUC(5 4 .0± 12 .8)min·μg/mL ;高剂量组VC(0 .0 14± 0 .0 0 2 )L ,CLs(0 .0 88± 0 .0 2 3)L/h ,T1/ 2α(3.9± 0 .3)min ,T1/ 2 β(2 4 .3± 5 .9)min ,曲线下面积AUC(4 2 0 .1± 74 .2 )min·μg/mL。 结论 马兜铃酸A在大鼠体内呈二室开放模型 ,进入体内分布迅速 ,同时自血浆中代谢消除也较快 ,T1/ 2 β随着剂量的增加明显延长 ,AUC与剂量不成比例 。
Purpose: To study the pharmacokinetics of aristolochic acid A in normal rats. Methods: Plasma concentration of aristolonchic acid A was assayed by high performance liquid chromatography (HPLC). The chromatographic condition was HYPERSIL-C18 column (5 μm, 40 mm x 200 mm), the liquid phase was methanol:tetrahydrofuran: 0.025 mol/L KH2PO4(pH=3.8) (44:6:50), the mobile phase rate was 1 mL/min, the wave length for detection was 315 nm Plasma aristolonchic acid A at different time was measured in SD rats after given intravenous aristolonchic acid A solution (0.5 and 2.5 mg/kg, n = 4, respectively). The data obtained was analysed by 3p97 pharmacokinetic program. Results: The main pharmacokinetic parameters were:in low-dosage group: VC(0.013 ± 0.004) L, CLs (0.206 ± 0.132) L/h, T1/2a (2.5 ± 0.8)min, T1/2β(10.9 ± 2.5) min, area under the curve (AUC) was (54.0 ± 12.8) min·μg/mL;in high-dosage group: VC(0.014 ± 0.002) L, CLs (0.088 ± 0.023) L/h, T1/2α(3.9 ± 0.3) min, T1/2β (24.3 ± 5.9) min, AUC (420.1 ± 74.2) min·μg/mL. Conclusions: Aristolochic acid A showed an open two compartment model in rats. It distributed rapidly after its entry into the body, and was also eliminated rapidly from the plasma. T1/2β extended significantly with the increase of aristolonchic acid A given. AUC was not in proportion to the dosage and had a characteristic of non-linear kinetics.
出处
《复旦学报（医学版）》
EI
CAS
CSCD
北大核心
2004年第6期562-564,共3页
Hehai University Journal of Medical Sciences
基金
国家自然科学基金资助项目 ( 3 990 0 193 )
