Pharmacokinetics and Nasal Residence Time of Nicorandil Thermosensitive Nasal Gel in Rats
OBJECTIVE To study the pharmacokinetics and nasal residence time of nicorandil(NIC)thermosensitive nasal gel in rats.METHODS The concentration of NIC in rat plasma was determined by HPLC method.Rats were randomly divided into nasal and intragastric groups of 6 animals each.NIC thermosensitive nasal gel was nasally administered to the test group at a dose of 2.5 mg·kg-1 and NIC suspension was given intragastricaly to the control group at a dose of 5.0 mg·kg-1.The drug plasma concen-trations at different times following administration were determined and the main pharmacokinetic parameters of NIC for the two groups such as tmax,ρmax,t1/2,AUC0-r,AUC0-∞ and relative bioavailability(Fr)for the NIC nasal gel were estimated.Furthermore,with dye method,the nasal residence time of the NIC nasal gel was investigated by using rats as test model and 0.9％NS as reference.RESULTS The tmax of the in group and ig group were 0.08 and 0.33 h,ρmax were 19.63 and 12.55 μg·mL-1,t1/2 were 2.63 and 2.27 h,AUC0-t were 22.04 and 28.93 μg·h·mL-1,AUC0-∞ were 24.54 and 30.42 μg·h·mL-1,respectively.The relative bioavailability(Fr)of the NIC nasal gel was found to be 161.34％.The nasal residence time of the NIC nasal gel and 0.9％NS were observed to be 13.4 and 2.2 min,respectively.CONCLUSION NIC thermosensitive nasal gel may be a new dosage form for treating angina pectoris with good clinical application prospect due to its rapid in vivo absorption,high bioavailability,longer nasal residence time and convenient administration.
nicorandilthermosensitive nasal gelpharmacokineticsbioavailabilitynasal residence time
万方数据
维普
