国产格列美脲片剂在健康男性志愿者的生物等效性评价

2002-03-30收稿　2002-07-24修回王少华,联系作者,女,主任药师,研究生导师,青岛市立医院国家药品临床研究基地副主任。主要从事临床药理学研究。Tel:[phone]　E-mail:[e-mail]国产格列美脲片剂在健康男性志愿者的生物等效性评价王少华,陈安进,于宝东,初晓,石杰,赵美玲(青岛市立医院国家药品临床研究基地,青岛　266011)　:以单剂量试验判定格列美脲片剂与参比胶囊剂的生物等效性。:20名健康男性志愿者随机分成两组,采用3mg单剂量(口服)交叉试验设计,以高效液相法测定血药浓度,以3p97药代动力学程序求算,等效性分析用双单侧t检验。:格列美脲片剂和参比胶囊剂的AUC(0-t)分别为(1.23±0.19)和(1.31±0.22)mg·h·L-1,AUC(0-inf)分别为(1.32±0.20)和(1.45±0.24)mg·h·L-1,Cmax分别为(0.30±0.05)和(0.30±0.06)mg·L-1,Tpeak分别为(2.43±0.29)和(2.55±0.46)h,T1/2Ke分别为(6.9±2.5)和(9.3±7.9)h。FAUC(0-t)=96.4±21.1,FAUC(0-inf)=93.7±20.7。:格列美脲片剂和参比胶囊剂生物等效。:格列美脲;高效液相色谱;生物等效性:R969.1:A:1009-2501(2002)05-0437-03。Ⅱ,FDA。,。。1　[1～3]1.1　　Waters600,Waters2487,Millennium32。3p97。(,:000717,1mg/),(HoechestMarionRousse,:40H487,1mg/);,。1.2　　20,23±3(20～28),173.3±4.3(164～185)cm,64.5±5.2(60～69)kg。,A1,B1。1wk,。1.3　1.3.1　色谱条件　Waters600;C18,5μm,4.6mm×150mm,Waters2487,361nm,25℃;:0.05mol·L-1HClO4∶(42∶58,v/v),2ml·min-1;100μl。:,100μg·L-11μg·L-1,:,5μg·L-1。,。1.3.2　血样采集　3mg,0.5,1.0,1.5,2.0,2.5,3.0,4.0,8.0,12,24h2ml,,20℃。1.3.3　血样处理　10min,3500r·min-15min,20℃。40μl1mlHCl-KCl(pH=1)1ml,5ml10min。3000r·min-130min,,。100μl2,4-(DNFB)(30μlDNFB10ml)120℃30min。60℃,200μl。437　ChinJClinPharmacolTher2002Oct;7(5):437-4392　2.1　2.1.1　标准曲线及最低检测限　0.50ml5,400,200,100,50,20,10,5μg·L-1。:R=0.0035×C-0.00191,r=0.9996,R,C,5μg·L-1(S/N≥3)。2.1.2　相对回收率及精密度　300、100、15μg·L-15,“”,。(101.00±6.39)%、(100.95±3.67)%、(98.40±5.03)%。1　(x±s,n=5)/μg·L-1RSD/%RSD/%150.0737±0.00182.450.0746±0.00374.911000.3708±0.00360.960.3670±0.00852.313001.0754±0.01151.071.0932±0.01841.682.2　　20,C-T(1)。3p97,2。2　3mg(x±s,n=20)AUC(0-t)/mg·h·L-11.23±0.191.31±0.22AUC(0-inf)/mg·h·L-11.32±0.201.45±0.24Cmax/mg·L-10.30±0.050.30±0.06Tpeak/h2.43±0.292.55±0.46T1/2Ke/h6.95±2.489.27±7.91F/%96.4±21.12.3　　FAUC(0-t)=96.4±21.1,FAUC(0-inf)=93.7±20.7,80%～120%。Cmax、Tpeak、AUC(0-t),(P0.05);t,Cmax90%88.5%～104.2%,75%～143%,AUC(0-t)90%85.7%～102.3%,80%～120%,。1　203mg3　,,400μg·L-1,[4,5],400μg·L-1。。,。,,。,。,t,。,。1　,,.[M].1.:,1999:3162　,,.[M].1.:,1999:1073　,.[M].1.:,2000:754　EmilssonH,SjobergS,SvednerM,etal.High-performanceliquidchromatographicdeterminationofglibenclamideinhumanplasmaandurine[J].JChromatogr,1986;383:93-1025　LehrKH,DammP.Simultaneousdeterminationofgliben-438　ChinJClinPharmacolTher2002Oct;7(5)clamide,chlorpropamideandtolbutamideinplasmabyhigh-performanceliquidchromatographywithultravioletdetection[J].JChromatogr,1985;339:203-9EvaluationofbioequivalenceofdomesticglimepiridetabletinChinesehealthymalevolunteersWANGShao-Hua,CHENAn-Jin,YUBao-Dong,CHUXiao,SHIJie,ZHAOMei-Ling(NationBaseofDrugClinicalTrialofQingdaoMunicipalHospital,Qingdao266011)ABSTRACT　AIM:Tocomparethebioequivalenceofglimepiridetablesandcapsuleswithasingledose.METHODS:TwentyChinesehealthymalevolunteerswereenrolledinarandomizedcrossoverstudywithasin-gleoraldose3mgoftwoformulationsrespectively.TheblooddrugconcentrationinserumwasmeasuredbyHPLC,andthepharmacokineticparameterswerecalcu-latedby3p97softwareandcomparedbytwoone-sidet-test.RESULTS:Theparametersofthetablesandthecapsuleswere(1.23±0.19)and(1.31±0.22)mg·h·L-1atAUC(0-t),(1.32±0.20)and(1.45±0.24)mg·h·L-1atAUC(0-inf),(0.30±0.05)and(0.30±0.06)mg·L-1atCmax,(6.6±2.5)and(9.3±7.9)hthepeaktime(Tpeak),respectively.Therewerenosignificantdifferencesbetweenthetwoformula-tions.Fwas96.4±21.1calculatedbyAUC(0-t)and96.4±21.1byAUC(0-inf).CONCLUSION:Glimepiridetablesandcapsulesareofbioequivalence.KEYWORDS　glimepiride;HPLC;bioequivalence欢迎订阅《世界临床药物杂志》(原国外医药———合成药、生化药、制剂分册》)《———、、》(ISSN1001-7247,CN31-1242/R)20,、,。2003《》,,、,,,。。200364,16,8。。。:1320;:200040;:021-62479808-314;:021-62890581;E-mail:[e-mail];:021-62896800;:021-62897080;:439　ChinJClinPharmacolTher2002Oct;7(5)