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Objectives: To study the effect of multiple doses of montelukast Sodium on the pharmacokinetics of doxophylline in rats.Materials andMethods: The pharmacokinetic interaction of doxophylline was studied in normal Sprague-Dawley rats with and without montelukast Sodium coadministration.Blood samples were analyzed using a validated high-performance liquid chromatography method to generate the pharmacokinetic profile of doxophylline.The Cmax were directly read from the concentration–time data.Other pharmacokinetic parameters were estimated using non-compartmental analyses.Results: Doxophylline was monitored up to 9 h.The rats administered with doxofylline dose alone showed the Cmax of doxofylline was 40.35±8.07μg/ml and the Tmax was 2.33±0.25.The AUC0-t and AUC0-∞ were 137.33 ± 27.29 and 143.43 ± 25.62 μg.h/ml,respectively.The mean residence time (MRT0-t) was 2.97±0.15 h.Apparent volume of distribution (Vd/F) and clearance (Cl/F) averaged to 381.17 ± 132.13 L/kg and 143.16 ± 25.35 L/h/kg,respectively.Following montelukast Sodium coadministration,doxofylline showed the Cmax of doxofylline was 48.94±5.91 μg/ml and Tmax was 0.833±0.258,earlier than that after doxofylline dosing alone.The AUC0-t and AUC0-∞ were significantly increased to 173.91±23.72(p < 0.05) and 198.79±47.81 μg.h/ml(p < 0.05),respectively.However,Cl/F (105.05±22.80,p < 0.05) was decreased than that after doxofylline dosing alone.MRT0-t(4.06±1.54h) and Vd/F were 2.85±0.44h and 373.81±134.96 L/kg,respectively,and were similar to the values obtained after doxofylline dosing alone.Conclusions: The results indicate that montelukast Sodium coadministration increases the rate but not the extent of absorption of doxofylline in rats.And it seem to inhibit CYP1A2-mediated hepatic doxofylline metabolism.