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Pharmacokinetics of dipyridamole-β-cyclodextrin complex in healthy volunteers after single and multiple doses

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Dipyridamole is a well known anti-aggregating agent characterized by poor water solubility as well as scant and variable bioavailability. Recently, the compound was complexed with β-cyclodextrin forming a molecular encapsulation resulting in better oral absorption and stronger biological activities in animals. In the present study, a randomized double blind cross-over comparison between dipyridamole-β-cyclodextrin complex (dip-β-CD) and dipyridamole was performed in 12 healthy subjects after single (75mg) and multiple oral treatments (75mg TTD). Dip-β-CD showed better bioavailability and less interindividual variability than dipyridamole either after single or multiple doses. In particular, dip-β-CD had a greater AUC and Cmax, and a smaller Tmax even at the steady state. Li addition, 100% of the subjects receiving a single dose of dip-β-CD, as compared to 66.7% of those treated with dipyridamole, had plasma levels superior to 1 μg/ml (which is the supposed anti-aggregating threshold level). In contrast, 0 and 33.03% of the subjects showed plasma levels superior to 2.5 μg/ml (which might cause the appearance of side-effects) on the 7th day of the multiple treatment with dip-β-CD and dipyridamole, respectively. In fact, the subjects presenting higher levels after uncomplexed dipyridamole also complained of headache and/or dizziness on occasion. No adverse side effects were reported for dip-β-CD.

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Correspondence to G. B. Fregnan.

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Ricevuti, G., Mazzone, A., Pasotti, D. et al. Pharmacokinetics of dipyridamole-β-cyclodextrin complex in healthy volunteers after single and multiple doses. European Journal of Drug Metabolism and Pharmacokinetics 16, 197–201 (1991). https://doi.org/10.1007/BF03189959

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  • Dipyridamole
  • cyclodextrin complexes
  • molecular encapsulation
  • bioavailability
  • anti-aggregating agents
  • coronary dilator