title: beta-cyclodextrin derivatives, SBE4-beta-CD and HP-beta-CD, increase the oral bioavailability of cinnarizine in beagle dogs.
abstract: 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.
authors.affiliation: Department of Pharmaceutical Chemistry, University of Kansas, Lawrence 66045, USA.
authors.forename: T
authors.initials: T
authors.lastname: Järvinen
authors.forename: K
authors.initials: K
authors.lastname: Järvinen
authors.forename: N
authors.initials: N
authors.lastname: Schwarting
authors.forename: V J
authors.initials: VJ
authors.lastname: Stella
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002936:Cinnarizine / Q000737:chemistry / Q000493:pharmacokinetics*; D003505:Cyclodextrins / Q000737:chemistry / Q000493:pharmacokinetics*; D004285:Dogs; D008297:Male; D013997:Time Factors
chemical_list: D003505:Cyclodextrins; D002936:Cinnarizine