Comparison of pharmacokinetics of Alprazolam after intranasal and intragastric administration in rats

作     者：GAO Yun-sheng,FEI Hong-rong,LI Ke,XIN Xiao-ming,QU Xiao-lan,QI Yong-xiu(School of Pharmacy,Taishan Medical University,Taian 271016,China) 

出 版 物：《沈阳药科大学学报》 (Journal of Shenyang Pharmaceutical University)

年 卷 期：2008年第25卷第S1期

页      面：101-102页

学科分类：1006[医学-中西医结合] 10[医学] 100602[医学-中西医结合临床] 

主　　题：Alprazolam intranasal administration pharmacokinetics RP-HPLC 

摘      要：Objective To compare the pharmacokinetics of Alprazolam after intranasal and intragastic administration in rats and evaluate the practicability of Alprazolam as a nasal drug delivery system.Methods 12 rats were randomly divided into two groups.The fate of drug in the serum of rats was monitered after intranasal and intragastic administration of Alprazolam 2 mg·kg-1.Serum levels of Alprazolam were determined by reversed-phase HPLC with Diode array detectors(DAD).Chromatographic conditions were adopted with ODS column as solid phase,methanaol-0.02 M ammonium acetate(pH=5.0)(60∶40)as mobile phase at a flow rate of 1.0 mL·min-1.The detection wavelength was 223 nm.The concentration-time data were analyzed using 3P87 program,and the pharmacokinetic parameters were compared by t-test.Results The pharmacokinetic characteristics were fit to two and one compartment opened model after intranasal and intragastic administration of Alprazolam,respectively.The drug absorption was quicker and the serum concentrations of Alprazolam was significantly higher in rats after intranasal administration group than that intragastic administration group(P0.05).Means of pharmacokinetic parameters in intranasal and intragastic groups were:Ka 37.35±22.98 vs 11.57±12.47 h-1(P0.05),t1/2β(t1/2Ke)2.51±0.99 vs 2.54±0.97 h(P0.05),tmax 0.156±0.069 vs 0.618±0.414 h(P0.01),Cmax 353.11±96.30 vs 62.09±35.08 μg·L-1(P0.01),AUC 1111.6±473.2 vs 274.1±185.3 μg·L-1·h(P0.01).Conclusions Alprazolam was absorbed quickly in rats after intranasal administration.And the serum concentration and bioavailability can be significantly increased after intranasal administration,which may be an effective preparation as nasal drug delivery system.