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.

journal_name

Biol Pharm Bull

authors

Yagi N,Taniuchi Y,Hamada K,Sudo J,Sekikawa H

doi

10.1248/bpb.25.1614

subject

Has Abstract

pub_date

2002-12-01 00:00:00

pages

1614-8

issue

12

eissn

0918-6158

issn

1347-5215

journal_volume

25

pub_type

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