title: Pharmacokinetics of ketotifen fumarate after intravenous, intranasal, oral and rectal administration in rabbits.
abstract: The pharmacokinetics of ketotifen fumarate (KF) was examined after administration in rabbits through four different routes (intravenous, intranasal, oral and rectal). The time-course of the plasma concentration of KF after intravenous administration (1 mg/kg dose) fitted a two-compartment open model. KF was rapidly absorbed and showed a high plasma concentration within 0.33 h after intranasal administration. The absolute bioavailability of KF after intranasal administration was 66%. After oral administration at a dose of 1 mg/kg, the plasma concentration of KF was below the detection limit of HPLC analysis. Even at 5 mg/kg, the value of the area under the plasma concentration-time curve (AUC) after oral administration of KF was significantly lower than that after intranasal administration of 1 mg/kg. Oral bioavailability was only 8%. The very low bioavailability of KF after oral administration might be due to the first-pass effect in the liver. We also prepared suppositories containing KF (1 mg/kg) for rectal administration in rabbits. After rectal administration, KF was rapidly absorbed and its bioavailability was 34%. These results indicated that the intranasal route appears the most effective for administering KF, and that rectal administration may be superior to oral administration in terms of bioavailability.
authors.affiliation: Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Japan. yagi@hoku-iryo-u.ac.jp
authors.forename: Naomi
authors.initials: N
authors.lastname: Yagi
authors.forename: Yoshikuni
authors.initials: Y
authors.lastname: Taniuchi
authors.forename: Keinosuke
authors.initials: K
authors.lastname: Hamada
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Sudo
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sekikawa
mesh_terms: D000281:Administration, Intranasal; D000284:Administration, Oral; D000285:Administration, Rectal; D000818:Animals; D019540:Area Under Curve; D007275:Injections, Intravenous; D007665:Ketotifen / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D011817:Rabbits
chemical_list: D007665:Ketotifen