双嘧达莫大鼠在体胃、肠吸收动力学研究

Absorption Kinetics of Dipyridamole in Rat Gastrointestinal

目的研究双嘧达莫(Dip)大鼠消化道在体吸收情况。方法采用HPLC测定各溶液中Dip的含量,测定不同pH溶液中Dip的溶解度,分别进行原位胃吸收、十二指肠、空肠、回肠、结肠单向灌流实验,并用SPSS进行统计学考察。结果Dip在盐酸溶液(9→1000)、pH2.5,4.5,6.8,7.4磷酸盐缓冲液和Krebs-Ringer缓冲液中的溶解度分别为(79096±329)、(1530±91)、(294.7±7.0)、(10.21±0.61)、(9.43±0.69)和(10.57±0.28)mg.L-1,溶解度和pH值近似满足如下关系S(mg.L-1)=450773.pH-5.3781(r=0.99);大鼠消化道各部位吸收速率常数分别为:胃(0.91±0.36)h-1、十二指肠(2.80±0.80)h-1、空肠(2.95±0.47)h-1、回肠(1.05±0.28)h-1、结肠(2.95±0.80)h-1。结论在胃液中Dip的溶解度显著高于其他肠段,且药物在消化道各段均有吸收,适合制成胃漂浮/滞留缓控释制剂。

OBJECTIVE To explore the absorption kinetics of dipyridamole in rat gastrointestinal （G1）. METHODS The concentrations of dipyridamole in different solutions were determined by HPLC. The solubility of dipyridamole in buffer solutions of different pH were studied. The absorption of dipyridamole in different parts of GI was studied by in situ stomach absorption experiments and one way perfusion experiments in duodenum, jejunum, ileum and colon. SPSS was employed to do statistic investigation. RESULTS The solubility of dipyridamole in buffer solutions ofHCl solution（9→ 1 000） at pH 2.5, 4.5, 6.8, 7.4 and in Krebs-Ringer buffer solution were （79 096±329）, （1 530±91）, （294.7±7.0）, （10.21±0.61）, （9.43±0.69） and （10.57±0.28） mg·L^-1 respectively. The relationship between solubility and pH was expressed as S（mg·L^-1）=450 773·pH^-5378 1 （r=0.99）. The permeability constants of dipyridamole were （0.91±0.36）, （2.80±0.80）, （2.95±0.47）, （1.05±0.28） and （2.95±0.80） h^-1 respectively in stomach, duodenum, jejunum, ileum and colon. CONCLUSION The solubility of dipyridamole went down with increasing of the pH. Dipyridamole could be absorbed by any part of the GI. Dipyridamole is a good candidate for floating modified-release preparations.