甲基斑蝥胺在大鼠胃肠道的吸收动力学

目的研究甲基斑蝥胺(MCD)在大鼠胃及肠道的吸收动力学特征。方法采用封闭灌注技术进行原位胃灌注吸收研究,在体循环法考察小肠全肠段吸收,采用单向肠灌流技术进行不同肠段吸收研究,建立HPLC法测定MCD的浓度,考察MCD大鼠胃肠吸收特征及吸收机制。结果 116.34mg·L~(-1)MCD在十二指肠、空肠、回肠、结肠及胃中的吸收速率常数(K_a)分别为(0.0635±0.0091)、(0.0687±0.0008)、(0.0315±0.0009)、(0.0399±0.0009)和(0.0033±0.0001)min~(-1),不同药物浓度59.55、116.34、204.15mg·L~(-1)时胃及空肠中的K_a分别为(0.0031±0.0001)、(0.0033±0.0001)、(0.0031±0.0001)min~(-1)及(0.0667±0.0010)、(0.0687±0.0008)、(0.0705±0.0011)min~(-1);在空肠不同pH值(5.0,6.2,7.4)时K_a分别为(0.0801±0.000 9)、(0.0783±0.0009)、(0.0758±0.0009)min~(-1)。MCD在胃中吸收很弱;在空肠、十二指肠、结肠和回肠中均有一定吸收,在空肠吸收最好,在肠中吸收呈一级动力学过程,吸收机制为被动扩散。MCD溶液浓度及pH值对其肠吸收速率无显著影响(P>0.05)。结论 MCD属于生物药剂学分类系统Ⅰ类药物。

Gastrointestinal absorption kinetics of methylcantharidimide in rats

AIM To investigate the absorption kinetics of methylcantharidimide(MCD) in gastrointestinal tract of rats.METHODS The absorption kinetics and mechanism of MCD were studied by in situ closed loop method and single-pass perfusion model.HPLC method was established to determine the concentration of MCD.RESULTS The absorption rate constants(K_a)of 116.34 mg·L~(-1) MCD at duodenum,jejunum,ileum, colon and stomach were(0.063 5±0.009 1),(0.068 7±0.000 8),(0.031 5±0.000 9),(0.039 9±0.000 9) and(0.003 3±0.000 1) min~(-1),respectively.At the concentration of 59.55,116.34,204.15 mg·L~(-1),K_a for the stomach and jejunum were(0.003 1±0.000 1),(0.003 3±0.000 1),(0.003 1±0.000 1) min~(-1) and(0.066 7±0.001 0),(0.068 7±0.000 8),(0.070 5±0.001 1) min~(-1),respectively.At pH of 5.0,6.2,7.4,K_a for jejunum were(0.080 1±0.000 9),(0.078 3±0.000 9),(0.075 8±0.000 9) min~(-1),respectively.The absorption of MCD was relatively poor in stomach.The absorption order was jejunum>duodenum>colon>ileum.The drug concentration and pH had little significant effect on the intestine absorption kinetics(P>0.05).CONCLUSION MCD belongs to biopharmaceutics classification systems I.Jejunum is the best site of absorption for MCD,whose mechanism is assumed to be absorbed by passive diffusion.