Aim To evaluate the relative bioavailability and the bioequivalence between two kinds of enalapril maleate tablets.Methods A single oral dose of enalapril maleate tablet was given respectively to 20 healthy volunteers in a two-way cross over test.Plasma concentration of enalapril maleate was determined by HPLC-MS-MS.Results The main pharmacokinetic parameters were as follows:Cmax,Tmax,t1/2,AUC(0-48h),AUC(0-∞)of test preparation and reference preparation were(32.74±9.01),(35.48±11.44)μg·L-1;(0.76± 0.17),(0.87±0.17)h;(2.52±2.95),(3.10±5.79)h;(59.22±20.46),(64.43±23.42)mg·h·L-1;(60.01±20.39),(65.09±23.43)mg·h·L-1,respectively,and F0-tn of test preparation was(97.8±34.1)%.Conclusion The test preparation is bioequivalent to the reference preparation.

OBJECTIVE To study the relative bioavailability and bioequivalence of isosorbide mononitrate pills in healthy volunteers.METHODS A single oral dose(40 mg of test and reference formulation)were given to 18 healthy volunteers in a randomised crossover study.The concentrations of isosorbide mononitrate in plasma were determined by HPLC.The pharmacokinetics parameters were calculated and the bioavailability and bioequivalence of two formulations were evaluated by DAS program.RESULTS After a single dose,the pharmacokinetics parameters for isosorbide mononitrate were as follows:Cmax(453.2±67.4)μg·L-1 and(434.3±63.2)μg·L-1;tmax(0.60±0.13)h and(0.69±0.14)h;AUC(0-36)(3013.7±576.3)μg·h·L-1 and(2974.2±754.4)μg·h·L-1;AUC(0-∞)(3156.0±582.8)μg·h·L-1 and(3 161.1±766.5)μg·h·L-1 for tested and reference formulation respectively.The 90% confidential interval of AUC(0-36)、AUC(0-∞)and Cmax of tested formulation were 95.8%-108.9%,94.8%-106.6% and 100.5%-108.2% respectively.The relative bioavailability was(103.4±16.9)%.CONCLUSION The results of the statistic analysis showed that the two formulations were bioequivalent.

OBJECTIVE To establish the high performance liquid chromatogram (HPLC) method for determining vitamin E nicotinate in healthy volunteers and study its pharmacokinetics process.METHODS A single oral dose (0.6 g) was given to 20 healthy volunteers in a randomised study. Collect venous blood at different time points in 36 h after administration. The concentrations of vitamin E nicotinate in plasma were determined by high performance liquid chromatography (HPLC). Calculate and evaluate the pharmacokinetics parameters of vitamin E nicotinate in human by DAS program.RESULTS Assay linearity was obtained in the range of (25.0-2000.0) g·L-1(r=0.999 9). The relative recovery of vitamin E nicotinate from Human plasma was in the range of (85-115)%. The absolute recovery was more than 70%. The intraday and interday relative standard deviations (RSD) were both less than 15 %. The concentration-time curve was fitted to a two-compartment model. Its main pharmacokinetic parameters were as follows: Tmax were (5.1±0.6) h; Cmax were (1 094.6±290.8) μg·L-1; T1/2 were (8.0±0.8) h; AUC (0-36); AUC (0-inf) were (10 953.5±2184.2) μg·h·L-1 and (11 532.8±2184.3) μg·h·L-1, respectively.CONCLUSION The method developed in this report had high sensitivity, good selectivity and reproducibility for accurate determination of the plasma concentration of vitamin E nicotinate in human, and fit to the pharmacokinetics study.

Objective: To study the relative bioavailability and bioequivalence of famciclovir tablets in healthy volunteers.Methods: A single oral dose of 0.5 g famciclovir(test or reference tablets) was administered to 18 healthy volunteers in a randomised crossover study.The concentrations of penciclovir in plasma were determined by HPLC.The pharmacokinetic parameters were calculated,and the relative bioavailability and bioequivalence of two tablets were evaluated by DAS program.Results: After single doses of test and reference tablets,the pharmacokinetic parameters of penciclovir were as follows: Cmax,(3.05±0.73) and(3.16±0.99) mg·L-1;Tmax,(1.03±0.47) and(1.15±0.62) h;AUC0~12,(9.11±2.75) and(9.53±2.68) mg·h·L-1;AUC0~inf,(9.49±2.98) and(9.89±2.76) mg·h·L-1,respectively.The 90% confidential intervals of AUC0~12,AUC0~inf and Cmax of test tablets were 87.7%~103.7%,87.9%~103.8% and 91.4%~106.4%,respectively.Conclusion: The relative bioavailability is(97.9±22.6)%;the two famciclovir tablets are bioequivalent.

目的:建立人血浆中依诺沙星浓度的高效液相色谱(HPLC)方法,研究口服单剂量依诺沙星片后健康志愿者体内的药物代谢动力学过程。方法:健康志愿者20名,单剂量口服依诺沙星片0.4g,分别于服药后24h内多点抽取静脉血。以HPLC法测定血浆中依诺沙星的浓度。以DAS药代动力学程序计算药动学参数,分析体内的药动学过程。结果:依诺沙星片在(0.05～6.0)mg·L-1范围内线性关系良好(r=0.9999),相对回收率均在85%～115%范围内,绝对回收率大于75%;日内和日间变异均小于15%。依诺沙星浓度主要药代动力学参数为:Tmax为(1.350±0.580)h;Cmax为(3.029±0.671)mg·L-1;T1/2为(5.835±0.908)h;AUC(0-24)、AUC(0-inf)分别为(17.678±2.899)mg·h·L-1和(18.685±3.172)mg·h·L-1。结论:本方法灵敏度高,选择性好,重现性佳,可准确测定人血浆中依诺沙星的浓度,适合药动学研究,为临床用药提供指导依据。

Objective To study the relative bioavailability and bioequivalence of Tinidazole tablets in Chinese healthy volunteers.Methods A single oral dose(1g of tested and reference formulation,the washout period was 2 weeks) were given to 20 healthy volunteers in a randomized crossover study,blood sampling was conducted consequently within 60 hours respectively.HPLC was used to determine the concentration of Tinidazole in plasma,and DAS program was used to evaluate the bioequivalence.Results After a single oral dose,the pharmacokinetics parameters for Tinidazole were as follows: Cmax were(21.38±3.64)mg·L-1 and(20.22±3.13)mg·L-1;Tmax were(1.83±1.16)h and(1.83±1.07)h;t1/2 were(15.17±1.60)h and(15.77±1.73)h;AUC(0-60) were(423.77±46.49)mg·h·L-1 and(405.36±39.73)mg·h·L-1;AUC(0-inf) were(454.73±50.89)mg·h·L-1 and(438.01±49.67)mg·h·L-1.The 90% confidence interval of AUC(0-60),AUC(0-inf) and Cmaxwere 101.3～107.7%,100.5～107.3% and 100.9～110.0%,respectively.The relative bioavailability was 104.73±7.91%.Conclusion The test and reference formulation are bioequivalence.

Objective:To study the bioequivalence of ibuprofen granules in healthy volunteers.Method:The concentrations of ibuprofen in plasma were determined by HPLC.A single oral dose (400 mg of tested and reference formulation) were given to 18 healthy volunteers in a randomised crossover study.The pharmacokinetics parameters were calculated and the bioequivalence of two for- mulations were evaluated by DAS program.Result:After a single dose,the pharmacokinetics parameters for ibuprofen were as follows: C_(max) were(39.35±5.42)μg·ml~(-1) and (40.10±6.33)μg·ml~(-1);t_(max) were (1.64±0.41) h and (1.58±0.19) h;AUC_((0-10)) were (142.70±25.02)μg·ml~(-1)·h and (150.29±18.24)μg·ml~(-1)·h~(-1);AUC_((0-inf)) were (152.93±28.14)μg·ml~(-1)·h and(161.18±19.59)μg·ml~(-1)·h for T and R respectively;the relative bioavailability was (95.97±18.91) %.Conclusion:The results of the sta- tistie analysis showed that the two formulations are bioequivalence.

OBJECTIVE To study the Pharmacokinetics and Bioequivalence of Omeprazole Enteric-coated Capsules in Chinese healthy volunteers.METHODS A single oral dose(40mg of tested and reference formulation) were given to 20 healthy volunteers in a randomised crossover study.The concentrations of Trimetazidine in plasma were determined by HPLC.The pharmacokinetics parameters were calculated and the bioavailability and bioequivalence of two formulations were evaluated by DAS program.RESULTS After a single dose,the pharmacokinetics parameters for Trimetazidine were as follows: Cmax were(1 146.77±386.58)ng·mL-1 and(1 138.93±360.90)ng·mL-1;Tmax were(2.40±0.53)h and(2.28±0.44)h;AUC(0-12) were(4 853.61±1 960.52)ng·h·mL-1 and(4 743.06±1 740.71)ng·h·mL-1;AUC(0-inf) were(5 111.76±2 031.72)ng·h·mL-1 and(4 942.71±1 833.39)ng·h·mL-1 for tested and reference formulation respectively.The 90% confidential interval of AUC(0-12),AUC(0-inf) and Cmax of tested formulation were 94.6%～106.3%,96.5%～107.2% and 95.9%～104.3% respectively.CONCLUSION The relative bioavailability was(101.32±14.90)%;The results of the statistic analysis showed that the two formulations were bioequivalence.

目的 研究氢氯噻嗪片的人体相对生物利用度和生物等效性.方法 健康志愿者20例,随机双交叉单剂量口服试验制剂氢氯噻嗪片(T)和参比制剂氢氯噻嗪片(a)50 mg,剂间间隔为2周.分别于服药后36 h内多点抽取静脉血;用高效液相色谱(HPLC)法测定血浆中氢氯噻嗪的浓度.用DAS药动学软件计算相对生物利用度并评价两种制剂生物等效性.AUC0-36,AUC0-inf和Cmax经方差分析和双单侧t检验,tmax进行秩和检验.结果 单剂量口服氢氯噻嗪片试验制剂和参比制剂后,血浆氢氯噻嗪Cmax分别为(277.41±45.43)和(275.33±38.30)μg·L-1;tmax分为(2.15±0.40)和(2.25±0.34)h;AUC0-36分别为(2 290.75±198.87)和(2 295.75±219.15)μg·h·L-1;AUC0-inf分别为(2 539.31±237.92)和(2 546.99±229.78)μg·h·L-1.AUC0-36、AVC0-inf和Cmax的0%可信区间分别为96.2%～103.7,.96.0%～103.5%和94.4%～106.7%.结论 试验制剂与参比制剂的人体相对生物利用度为(100.36±10.14)%,两制剂具有生物等效性.

OBJECTIVE The relative bioavailabilites and bioequivalence of Anmaweiming tablets(tested) and reference tablets were studied.METHODS Two tablets was given,in a randomized,two-way crossover study,in 18 healthy male volunteers.The concentrations in plasma were determined by LC-MS/MS.RESULTS Based on the analysis by DAS program.,the pharmacokinetic parameters of test tablets and reference tablets were as follows:Psendoephedrine Hydrochloride:t1/2(4.3±1.6)h and(4.0±1.5)h,Tmax(1.8±1.3)h and(1.9±1.0) h,Cmax(463.3±149.7) μg·L-1and(462.6±193.6) μg·L-1,the relative bioavailabilites is(105.7±44.6)%;Chlorphenamine Maleate:t1/2(20.0±8.2)h and(18.2±8.5)h,Tmax(3.0±1.3)h and(3.2±1.6)h,Cmax(8.8±3.8) μg·L-1 and(9.3±4.5) μg·L-1,the relative bioavailabilites is(104.0±38.3)%;Dextromethorphan Hydrochloride:t1/2(4.0±1.4)h and(3.8±1.7)h,Tmax(2.6±1.2)h and(2.9±2.1)h,Cmax(5.8±6.8) μg.L-1 and(5.8±6.8) μg·L-1,the relative bioavailabilites is(93.7±25.3)%;Paratamal:t1/2(3.1±1.4)h and(3.2±1.6)h,Tmax(1.2±0.8) h and(1.2±0.6) h,Cmax(9 924.5±4 419.6) μg·L-1 and(10131.1±5320.3) μg·L-1,the relative bioavailabilites is(112.3±57.9)%.CONCLUSION The results of statistical analysis show that two formulations are bioequivalent.

Objective To study the relative bioavailability and bioequivalence of omeprazole Enteric-coated capsules in healthy volunteers. Methods A single oral dose(40 mg of tested and reference formulation) was given to 20 healthy volunteers in a randomised crossover study,with one week dose interval.The plasma omeprazole concentrationswas determined within 12 h administration by HPLC.The pharmacokinetics parameters were calculated and the bioavailability and bioequivalence of two formulations were evaluated by DAS program.AUC(0-12),AUC(0-inf) and Cmax was analysed by ANOVA followed by test,tmax was analysed by rank sum test. Results After a single dose administration,the pharmacokinetics parameters for omeprazole were as follows: Cmax were(939.63±284.29) μg·L-1 and(1 012.88±315.68) μg·L-1;tmax were(2.58±0.65) and(2.45±0.48) h;AUC(0-12) were(3 857.43±1 146.46) and(4 091.39±1 175.82) μg·h·L-1;AUC(0-inf) were(4 088.97±1 253.34)and(4 387.24±1 290.20) μg·h·L-1 for T and R respectively.The 90% confidential interval of Cmax,AUC(0-12) and AUC(0-inf) of tested formulation were 86.0%～101.7%,88.9%～101.5% and 87.3%～100.9% respectively. Conclusion The relative bioavailability of the tested and reference formulations was(96.26±16.52)%;The statistic analysis shows that the two formulations were bioequivalence.

OBJECTIVE To study the pharmacokinetics and relative bioavailability and bioequivalence of Gatifloxacin dispersible tablets in healthy volunteers.METHODS A single oral dose(400 mg of tested and reference formulation) was given to 20 healthy volunteers in a randomised crossover study.The concentrations of Gatifloxacin in plasma were determined by HPLC.The pharmacokinetics parameters were calculated and the bioavailability and bioequivalence of two formulations were evaluated by DAS program.RESULTS After a single dose,the pharmacokinetics parameters for gatifloxacin were as follows: Cmax were(3.75±0.74)mg·L-1 and(3.88±0.7) mg·L-1;Tmax were(0.81±0.31)h and(1.31±0.55)h;AUC(0-24) were(18.48±3.69)mg·h·L-1 and(18.45±2.67)mg·h·L-1;AUC(0-inf) were(19.24±3.64)mg·h·L-1 and(19.20±2.66)mg·h·L-1 for T and R respectively.The 90% confidential interval of AUC(0-24),AUC(0-inf) and Cmax of tested formulation were 91.8%-107.2%,92.1%-107.2%,90.4%-103.0%.CONCLUSION The relative bioavailability was(101.01±19.26)%;The results of the statistic analysis showed that the two formulations were bioequivalent.

目的 研究奥美拉唑肠溶胶囊的人体相对生物利用度和生物等效性.方法 健康志愿者20例,随机双交叉单剂量口服奥美拉唑肠溶胶囊的试验和参比制荆,剂量均为40 mg,剂间间隔1周.分别于服药后12 h内多点抽取静脉血;用高效液相色谱(HPLC)法测定血浆中奥美拉唑的浓度.用DAS药代动力学程序计算相对生物利用度并评价两种制剂生物等效性.AUC(0-12),AUC(0-inf)和Cmax经方差分析和双单侧t检验,tmax进行秩和检验.结果 单剂量口服奥美拉唑肠溶胶囊试验和参比制剂后,血浆奥美拉唑的Cmax分别为(939.63±284.29)和(1012.88±315.68)μg·L-1;tmax分别为(2.58±0.65)和(2.45 ±0.48)h;AUC(0-12)分别为(3857.43±1146.46)和(4091.39±1175.82)μg·h·L-1;AUC(0-inf)分别为(4088.97±1253.34)和(4387.24±1290.20)μg·h·L-1.Cmax、AUC(0-12)、AUC(0-inf)的90%可信区间分别为86.0%～101.7%,88.9%～101.5%和87.3%～100.9%.结论 试验制剂与参比制剂比较,其人体相对生物利用度为(96.26±16.52)%,两制剂具有生物学等效性.

Objective To develop a HPLC-MS/MS method for the determination of colchicine in human plasma,and to study its pharmacokinetics in healthy volunteers. Methods The plasma were extracted by Ethyl ether and dichloromethane.The analytical column was packed with ZORBAX Extend-C18.The mobile phase was Methanol-10 mmol·L-1 ammonium acetate and the flow rate was 1.1 mL·min-1.The selected ion was determined by ESI+.The colchicine concentrations of plasma were detected in 12 healthy volunteers at different time after they had been orally given 2 mg colchicines.The pharmacokinetic parameters were obtained with the DAS 2.0 program. Results Excellent liner relationship was obtained from the range of 0.05 μg·L-1 to 10 μg·L-1.The mean recovery rate was 92.47±1.73%,the RSDs of intra-and inter-day were less than 2.99% and 2.22% respectively. Conclusion The method is simple,rapid,accurate and can be used to determine the colchicine concentration in human plasma and to study its pharmacokinetics.

Objective:To develop an HPLC method for the determination of trimetazidine hydrochloride in human plasma.Methods:The plasma was extracted by ethyl acetate and n-henaxe.The analytical column was packed with ZORBAX Eclipse XDB-C_(18)(4.6 mm×150 mm,5μm)column.The mobile phase consisted of acetonitrile-0.1 mol ·L~(-1)sodium dihydrogen phosphate-0.1% trifluoroacetic acid-water(10:10:20:60)and the flow rate was 0.8 mL·min~(-1).The UV detection wavelength was 234 nm.Results:Excellent linear relationship was obtained in the range of 2.5μg·L~(-1)to 200μg·L~(-1)(r=0.9999);the determination limit of trimetazidine was 2.5μg·L~(-1);the relative recoveries(n=5)were(100.6±2.31)%,(99.84±7.53)% and(99.89±2.63)% respectively at low, middle,high concentrations;the intra-day RSDs(n=5)were 7.24%,2.61% and 5.45% and inter-day RSDs (n=5)were 5.64%,1.99% and 2.76%,respectively.Conclusion:The method is simple,rapid,accurate and can be adopted to determine the trimetazidine concentration in human plasma and for its pharmacokinetics study.

AIM To study the relative bioavailability and bioequivalence of glipizide orally disintegrating tablets in healthy volunteers.METHODS A single oral doses(10 mg of tested and reference formulations) were given to 20 healthy volunteers in a randomised crossover study.The concentrations of glipizide in plasma were determined by HPLC.The pharmacokinetic parameters were calculated and the bioavailability and bioequivalence of two formulations were evaluated by DAS program.RESULTS After a single dose,the pharmacokinetic parameters for glipizide were as follows: ρmax were(930.16±171.63)μg·L-1 and(915.12±126.11)μg·L-1;tmax were(3.05±0.94)h and(3.85±1.39)h;AUC0→24 were(8 220.93±1 162.94)μg·h·L-1 and(7 927.13±1 158.82)μg·h·L-1;AUC0→∞ were(8 821.76±1 323.28)μg·h·L-1 and(8 303.96±1 239.24) μg·h·L-1 for tested and reference formulations respectively.The 90% confidence interval of ρmax、AUC0→24 and AUC0→∞ of tested formulation were 94.82%-107.46%、99.76%-108.10% and 101.93%-110.84% respectively.CONCLUSION The relative bioavailability is(104.5±12.0)%.The results of the statistic analysis show that the two formulations are bioequivalence.

Objective To study the relative bioavailability and bioequivalence of isosorbide mononotrate tablets in healthy volunteers.Methods A single oral dose(40mg of respective test and reference) was given to 18 healthy volunteer in a randomized crossover study with an interval of one week.Blood samplings were conducted consequently within 24 hours;the concentrations of isosorbide mononotrate in plasma were determined by high-performance liquid chromatography(HPLC). The relative bioavailability was calculated and bioequivalence was evaluated by DAS program.Analysis of variance and two one sides t test were used to test AUC(0-24),AUC(0-∞),and Cmax;rank test was used to test Tmax.Results After a single oral dose of test and reference preparations,Cmax of isosorbide mononotrate in plasma was 424.28±43.09μg·L-1 and 442.48±57.78μg·L-1, respectively;Tmax was 1.11±0.21h and 1.06±0.24h respectively;AUC(0-24) was 2855.09±276.27μg·h·L-1 and 3028.28±296.00μg·h·L-1;respectively;AUC(0-inf) was(3046.40±314.61) μg·h·L-1 and(3312.46±382.60) μg·h·L-1 respectively.The 90% confidence interval of AUC(0-24),AUC(0-∞) and Cmax was 90.3%～98.5%,87.2%～97.1% and 92.6%～99.9% respectively.Conclusions The relative bioavailability of test and reference preparations was(94.79±10.14)%,the two preparations are bioequivalent.

OBJECTIVE To study the relative bioavailability and bioequivalence of domperidone orally disintegrating tablets in healthy volunteers.METHODS A single oral dose(20 mg of test and reference formulation) were given to 18 healthy volunteers in a randomised crossover study.The concentrations of domperidone in plasma were determined by HPLC.The pharmacokinetics parameters were calculated and the bioavailability and bioequivalence of two formulations were evaluated by DAS program.RESULTS After a single dose,the pharmacokinetics parameters for domperidone were as follows:Cmax were(31.0±5.5)μg·L-1 and(33.7±10.8)μg·L-1;Tmax were(0.56±0.14) h and(0.63±0.13) h;AUC(0-36) were(204.2±85.0)μg·h·L-1 and(186.8±58.6)μg·h·L-1;AUC(0-inf) were(244.8±114.1)μg·h·L-1and(215.4±56.5)μg·h·L-1 for T and R respectively.The 90% confidential interval of Cmax、AUC(0-36) and AUC(0-inf) of the test formulation were 86.3-104.8%,96.2-116.5% and 94.4-120.8% respectively.CONCLUSION The relative bioavailability is(108.5±25.1)%;The results of the statistic analysis show that the two formulations are bioequivalent.

Objective To study the relative bioavailability and bioequi-valence of sertraline hydrochloride dispersible tablets in healthy volunteers. Methods A single oral dose (100 mg of tested and reference formulation) were given to 20 healthy volunteers in a randomised crossover study. The concentrations of srtraline in plasma were determined by HPLC. The pharmacokinetic parameters were calculated and the bioavai-lability and bioequivalence of two formulations were evaluated by DAS program.Results After a single dose, the pharmacokinetic parameters for srtraline were as follows: Cmax were (42.11±3.48),(42.76±4.19)μg·L-1; tmax were (3.45±0.51),(4.60±0.94) h ; AUC(0-120) were (1.61±0.17),(1.60±0.20) mg·h·L-1; AUC(0-∞) were (1.68±0.18),(1.68±0.20) mg·h·L-1 for tested and reference formulation respectively. Te relative bioavailability was (101.08±9.10)%.Conclusion The results of the statistic analysis showed that the two formulations were bioequivalence.

OBJECTIVE To study the relative bioavailability of Dioxopromethazine Hydrochloride granules in healthy volunteers.METHODS A single oral dose (9 mg of tested and reference formulation) was given to 18 healthy volunteers in a randomized crossover study. The concentrations of Dioxopromethazine Hydrochloride in plasma were determined by HPLC. The pharmacokinetic parameters were calculated and the bioavailability and bioequivalence of two formulations were evaluated by DAS program.RESULTS After a single dose,the pharmacokinetic parameters for Dioxopromethazine Hydrochloride were as follows: ρmax (30.548±5.373) and (29.670±4.970) μg·L-1;tmax (2.833±1.225) and (2.593±1.798)h; AUC0-60 (436.722± 95.713) and (433.668±83.881) μg·h·L-1;AUC0-inf (455.990±105.688) and (448.718±84.741) μg·h·L-1 for T and R respectively. The 90% confidential interval of ρmax,AUC0-60 and AUC0-inf of tested formulation were 98.0%～107.9%,95.7%～105.0% and 95.1%～107.0%,respectively.CONCLUSION The relative bioavailability was (101.3±15.2)%.The results of the statistic analysis showed that the two formulations were bioequivalence.