Fregnan G B, Bertè F
Research Center, Edmond Pharma, Milan, Italy.
Pharmacology. 1990;40(2):96-102. doi: 10.1159/000138647.
Dipyridamole forms an inclusion complex with beta-cyclodextrin (dip-beta-CD) which shows better solubility and bioavailability than the uncomplexed compound. The present studies have demonstrated that dip-beta-CD is more effective than dipyridamole either as base or HCl (dispersed or not in lactose) on some important cardiovascular parameters when orally administered to conscious animals. In particular, dip-beta-CD causes a stronger and prompter coronary and carotid vasodilatation in dogs, at doses which weakly influence the systemic arterial pressure and the heart rate. In addition, platelets collected from treated rabbits at various intervals appear to be protected from sodium adenosine diphosphate-induced aggregation in vitro more effectively and rapidly by dip-beta-CD than by dipyridamole. Studies on tail bleeding time have confirmed that dip-beta-CD is more active than dipyridamole when given orally to mice. These biological findings are fully in agreement with other oral bioavailability studies in dogs and men indicating that dip-beta-CD gives quicker and higher blood levels with smaller interindividual variability than dipyridamole.
双嘧达莫与β-环糊精形成包合物（双嘧达莫-β-环糊精），该包合物比未复合的化合物具有更好的溶解性和生物利用度。目前的研究表明，当口服给予清醒动物时，双嘧达莫-β-环糊精在一些重要的心血管参数方面比作为碱基或盐酸盐形式（无论是否分散在乳糖中）的双嘧达莫更有效。特别是，在对全身动脉血压和心率影响较弱的剂量下，双嘧达莫-β-环糊精能使犬的冠状动脉和颈动脉产生更强、更迅速的血管舒张。此外，在不同时间间隔从经处理的兔采集的血小板，在体外似乎比双嘧达莫更有效、更迅速地受到双嘧达莫-β-环糊精的保护，免受二磷酸腺苷诱导的聚集。对小鼠尾部出血时间的研究证实，口服给予小鼠时，双嘧达莫-β-环糊精比双嘧达莫更具活性。这些生物学发现与在犬和人体进行的其他口服生物利用度研究完全一致，表明与双嘧达莫相比，双嘧达莫-β-环糊精能更快、更高地达到血药浓度，个体间变异性更小。
