Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Järvinen, T. et al.

beta-cyclodextrin derivatives, SBE4-beta-CD and HP-beta-CD, increase the oral bioavailability of cinnarizine in beagle dogs.

The absolute bioavailabilities (Fabs) of cinnarizine after oral administration as two modified beta-cyclodextrin (SBE4-beta-CD or HP-beta-CD) solutions, an aqueous suspension, and two capsules in fasted beagle dogs were determined. Cinnarizine was administered orally (25.0 mg) and intravenously (12.5 mg) to four dogs. Blood samples were drawn for 24.5 h postdosing, and cinnarizine levels in plasma were determined by HPLC with spectrofluorometric detection. Cinnarizine pharmacokinetics after iv administration as a 1.25 mg/mL SBE4-beta-CD solution followed triexponential behavior (t1/2 = 12.6 +/- 0.4 h and CI = 1.4 +/- 0.17 L/h/kg). A very low bioavailability of cinnarizine with a wide interanimal variation was observed after oral administration as a suspension (Fabs = 8 +/- 4%) or capsule containing only cinnarizine (Fabs = 0.8 +/- 0.4%). Administration of cinnarizine as a CD complex either as a solution (Fabs = 55-60%) or in a capsule (Fabs = 38 +/- 12%) significantly enhanced the bioavailability. Since the solutions showed excellent bioavailability, the logical conclusion is that, once presented as a solution, cinnarizine is well absorbed and that cinnarizine rapidly dissociates from its inclusion complexes. Presumably, the elevated bioavailability from the SBE4-beta-CD containing capsule was due to rapid dissolution and release of cinnarizine.[1]

References

beta-cyclodextrin derivatives, SBE4-beta-CD and HP-beta-CD, increase the oral bioavailability of cinnarizine in beagle dogs. Järvinen, T., Järvinen, K., Schwarting, N., Stella, V.J. Journal of pharmaceutical sciences. (1995) [Pubmed]

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