Aim To establish a LC-MS method for determining the concentration of nifedipine in human plasma and to evaluate the pharmacokinetic characteristics of nifedipine sustained-release tablets. Methods A XB-C18 （5 μm, 4....Aim To establish a LC-MS method for determining the concentration of nifedipine in human plasma and to evaluate the pharmacokinetic characteristics of nifedipine sustained-release tablets. Methods A XB-C18 （5 μm, 4.6 mm ×150 mm） column and a mobile phase of methanol： 0.01 mol·L^-1ammonium acetate （60：40, V/V） were used to separate nifedipine, the detections was accuracy under atmosperic pressure electronic spray ionization （AP-ESI） mode and ion mass spectrum （m/z） of 314.9 [M＋H]^＋ for nifedipine, and 320.8 [M＋H]^＋ for lorazepam （Internal Standard, IS）. Results The linear range of nifedipine was 0.3 - 80 ng·mL^-1 （ r = 0.9997）, and the limit of quantitation （LOQ） was 0.3 ng·mL^-1. The nifedipine pharmacokinetic parameters after a single dose of 20 mg nifedipine sustained-release tablets test （T） or reference （R） were as the followings, t1/2 （6.73 ± 2.00） h and （7.04 ± 2.18） h, Tmax （4.28 ± 0.70） h and （4.48 ± 0.70） h, Cmax（39.66 ± 10.58） ng·mL^-1 and （40.19 ± 10.97） ng·mL^-1, AUC0-36 （391.63 ± 108.55） ng·mL^-1·h and （387.57 ± 121.51） ng·mL^-1·h, and AUC0-∞ （408.28 ± 121.16） ng·mL^-1·h and （406.15 ± 133.13） ng·mL^-1·h. The relative bioavailability of nifedipine sustained-release tablets （test） was （103.02 ± 13.93） %. Conclusion LC-MS method for the determination of concentrations of nifedipine in human plasma was sensitive and accurate, and could be used in nifedipine bioavailability and pharmacokinetic studies.展开更多
Aim To evaluate the pharmacokinetics and bioequivalence of domestic pantoprazole sodium enteric-coated tablets as compared with imported pantoprazole enteric-coated tablets. Methods This was an open randomized, two pe...Aim To evaluate the pharmacokinetics and bioequivalence of domestic pantoprazole sodium enteric-coated tablets as compared with imported pantoprazole enteric-coated tablets. Methods This was an open randomized, two periods cross over study on twenty healthy male volunteers. The pantoprazole concentrations in plasma after an oral dose of 40 mg pantoprzaole preparations were determined by a HPLC-UV method. Non-compartmental method was used for the calculation of pharmacokinetic parameters. Logarithm-transformed Cmax and A UC were analyzed by the analysis of variance （ANOVA） with 90% confidence intervals. Results The main pharmacokinetics parameters of domestic pantoprazole sodium enteric-coated tablets and imported pantoprazole sodium enteric-coated tablets were as following： Cmax （3610 ± 956）, （3466 ± 1209） ng·mL^-1, tmax （3.00 ± 0.40）, （3.00 ± 0.46） h, AUC0-t （8140 ± 5065）, （8390 ± 5474） ng·h·mL^-1, AUC0-∞ （8293 ± 5094）, （8625 ± 5606） ng·h·mL^-1, t1/2 （1.61 ± 0.28）, （1.85 ± 0.27） h, respectively. Conclusion Domestic pantoprazole sodium enteric-coated tablets were bioequivalent with the imported pantoprazole sodium enteric-coated tablets.展开更多
Aim To develop a rapid, simple, and sensitive high-performance liquid chromatographic (HPLC) method for the determination of cefprozil in human plasma and to study its pharmacokinetics and bioequivalence after 0.5 g o...Aim To develop a rapid, simple, and sensitive high-performance liquid chromatographic (HPLC) method for the determination of cefprozil in human plasma and to study its pharmacokinetics and bioequivalence after 0.5 g oral doses of cefprozil granules and tablets. Methods The blood concentration of cefprozil was analyzed after extracted with 6% trichloroacetic acid, using tinidazole as internal standard (I.S.). A C_ 18 column was used to separate cefprozil with mobile phase of methanol, purified water and glac...展开更多
Aim To establish a HPLC method for the determination of bicalutamide plasma concentration and to evaluate the bioequivalence of bicalutamide capsules （test） and tablets （reference）. Methods A single oral dose of 5...Aim To establish a HPLC method for the determination of bicalutamide plasma concentration and to evaluate the bioequivalence of bicalutamide capsules （test） and tablets （reference）. Methods A single oral dose of 50 mg bicalutamide capsules or tablets were given to 48 Chinese healthy volunteers in a one period parallel design test. Bicalutamide in plasma was analyzed using a XB-C18 column with a mobile phase of acetonitrile-water （60：40, V/V） and the dectection wavelength of 272 nm and it is pharmacokinetic parameters were calculated and evaluated using DAS2.0. Results The linear range of bicalutamide was 10 - 1200 ng·mL^-1. The main pharmacokinetic parameters of the test and reference were as the followings, t1/2 （138.36 ± 32.03） and （146.12 ± 27.04） h, Tmax （17.17 ± 4.65） and （16.92 ± 4.85） h, Cmax（910.83 ± 130.49） and （868.71 ± 115.35） ng·mL^-1 AUC0-672（172437.08 ± 3986.07） and （176842.34 ± 35733.85） ng·mL^-1·h, and AUC0-∞ （179456.55 ± 43127.65） and （185270.39 ± 39688.63） ng·mL^-1·h, respectively. The two-one side t-test analysis showed that the confidence intervals of Crux, A UC0-672 and A UC0-∞ were （98.9% - 100.7%）, （98.8% - 100.6%） and （99.7% - 101.7%）, respectively. Conclusion The relative bioavailability of bicalutamide capsules was 97.51%. The bioequivalence was demonstrated by the two-one side t-test展开更多
AIM： To evaluate the bioequivalence of ranitidine and bismuth derived from two compound preparations. METHODS： The bioavailability was measured in 20 healthy male Chinese volunteers following a single oral dose （eq...AIM： To evaluate the bioequivalence of ranitidine and bismuth derived from two compound preparations. METHODS： The bioavailability was measured in 20 healthy male Chinese volunteers following a single oral dose （equivalent to 200 mg of ranitidine and 220 mg of bismuth） of the test or reference products in the fasting state. Then blood samples were collected for 24 h. Plasma concentrations of ranitidine and bismuth were analyzed by high-performance liquid chromatography and inductively coupled plasma-mass spectrometry （ICPMS）, respectively. The non-compartmental method was used for pharmacokinetic analysis. Log-transformed Cmax, AUC（0-t） and AUC（0-∞） were tested for bioequivalence using ANOVA and Schuirmann two-one sided t-test. Tmax was analyzed by Wilcoxon＇s test. RESULTS： Various pharmacokinetic parameters of ranitidine derived from the two compound preparations, including Cmax, AUC（0-t）, AUC（0-∞）, Tmax and T1/2, were nearly consistent with previous observations. These parameters derived from test and reference drug were as follows： Cmax（0.67 ± 0.21 vs 0.68 ± 0.22 mg/L）, AUC（0-t）（3.1 ± 0.6 vs 3.0 ± 0.7 mg/L per hour）, AUC（0-∞）（3.3 ± 0.6 vs 3.2 ± 0.8 mg/L per hour）, Tmax （2.3 ± 0.9 VS 2.1 ± 0.9 h） and T1/2 （2.8 ± 0.3 vs 3.1 ± 0.4 h）. In addition, double-peak absorption profiles of ranitidine were found in some Chinese volunteers. For bismuth, those parameters derived from test and reference drug were as follows： Cmax （11.80 ± 7.36 vs 11.40 ± 6.55 μg/L）, AUC（0-t） （46.65 ± 16.97 vs 47.03 ± 21.49 μg/L per hour）, Tmax （0.50 ± 0.20 vs 0.50 ± 0.20 h） and T1/2 （10.2 ± 2.3 vs 13.0 ± 6.9 h）. Ninety percent of confidence intervals for the test/reference ratio of Cmax, AUC（0-t） and AUC（0-∞） derived from both ranitidine and bismuth were found within the bioequivalence acceptable range of 80%-125%. No significant difference was found in Tmax derived from both ranitidine and bismuth. CONCLUSION： The two compound preparations are bioequivalent and may be prescribed interchangeably.展开更多
Gelatin has been used in hard capsule shells for more than a century, and some shortcomings have appeared, such as high moisture content and risk of transmitting diseases of animal origin to people. Based on available...Gelatin has been used in hard capsule shells for more than a century, and some shortcomings have appeared, such as high moisture content and risk of transmitting diseases of animal origin to people. Based on available studies regarding gelatin and vegetable shells, we developed a new type of algal polysaccharide capsule (APPC) shells. To test whether our products can replace commercial gelatin shells, we measured in-vivo plasma concentration of 12 selected volunteers with a model drug, ibuprofen, using high performance liquid chromatography (HPLC), by calculating the relative bioavailability of APPC and Qualicaps referenced to gelatin capsules and assessing bioequivalence of the three types of shells, and calculated pharmacokinetic parameters with the software DAS 2.0 (China). The results show that APPC shells possess bioequivalence with Qualicaps and gelatin shells. Moreover, the disintegration behavior of four types of shells (APPC, Vegcaps , Qualicaps and gelatin shells) with the content of lactose and radioactive element (99mTc) was observed via gamma-scintigraphic images. The bioavailability and gamma-scintigraphic studies showed that APPC was not statistically different from other vegetable and gelatin capsule shells with respect to in-vivo behavior. Hence, it can be concluded that APPCs are exchangeable with other vegetable and gelatin shells.展开更多
In the present study, we determined the pharmacokinetics and bioequivalence of two amlodipine tablets in Chinese male and female volunteers using HPLC-MS/IVIS method. A randomized, two-period and crossover design was ...In the present study, we determined the pharmacokinetics and bioequivalence of two amlodipine tablets in Chinese male and female volunteers using HPLC-MS/IVIS method. A randomized, two-period and crossover design was conducted in 20 healthy volunteers （14 male subjects and six female subjects）. A single dose of either the reference or test formulation was given at the start of each period. Blood samples were collected before drug administration and at 1, 2, 3, 4, 5, 6, 8, I0, 12, 24, 48, 72, 96, 120 and 144 h after drug administration. Plasma amlodipine was detected by HPLC-MS/MS method, and the pharmacokinetic parameters were analyzed using DAS 3.2.8. The developed HPLC-MS/MS method was suitable for the analysis of amlodipine in biological matrix samples. The main pharmacokinetic parameters between the trial preparation and the reference preparation met the regulatory criteria for bioequivalence, and the two preparations were both well tolerated.展开更多
The clinical pharmacokinetics of osmotic pump controlled release tablets of terazosin hydrochloride in healthy volunteers was studied.A sensitive and rapid HPLC method was used to determine the terazosin plasma concen...The clinical pharmacokinetics of osmotic pump controlled release tablets of terazosin hydrochloride in healthy volunteers was studied.A sensitive and rapid HPLC method was used to determine the terazosin plasma concentrations,and single and multiple doses of terazosin hydrochloride regular tablets（reference tablets）and osmotic pump controlled release tablets were orally administrated in randomized crossover design.The results showed that the C_（max）of the reference tablets after single oral dose（（120.56±23.15）ng/mL）in 20 healthy volunteers was significantly higher than that of controlled release tablets （（95.27±16.35）ng/mL）.The T_（max）of the controlled release tablets（（2.65±0.82）h）was significantly longer than that of reference tablets（（1.27±0.61）h）（P0.05）.The relative bioavailability of the controlled release tablets was found to be（105.85±6.12）%. The multiple oral dose pharmacokinetic parameters of the regular tablets and controlled release tablets were as follows：AUC_（SS） were（1275.17±175.35）and（1382.65±205.31）ng·h/mL respectively,C_（max）were（128.15±22.37）and（98.57±18.16）ng/mL respectively,T_（max）were（1.35±0.71）and（2.76±0.85）h respectively,C_（av）were（53.13±9.12）and（57.61±9.25）ng/mL respectively, and DF were（2.25±0.26）%and（1.62±0.25）%respectively.The relative bioavailability of the controlled release tablets to the reference tablets was（108.43±6.26）%.The controlled release tablet of terazosin hydrochloride was bioequivalent to the reference tablet.The controlled release tablet exhibited a sustained-release property with a significantly longer T_（max）and lower C_（max）.展开更多
In the present study, we aimed to compare the pharmacokinetics and pharmacodynamics between Glucophage~? and a generic metformin formulation in a diabetic rat model in order to assess the bioequivalence of the generic...In the present study, we aimed to compare the pharmacokinetics and pharmacodynamics between Glucophage~? and a generic metformin formulation in a diabetic rat model in order to assess the bioequivalence of the generic formulation. Adult male Zucker diabetes fatty rats received Glucophage~? or the generic metformin through gastric gavage at a dose of 180 mg/kg(n = 6 per condition). Both pharmacokinetic parameters(AUC0–t, AUC0–∞, Cmax) of metformin and plasma glucose levels were compared between the two groups. For pharmacodynamics, rats received Glucophage~? or the generic metformin at doses of 180 and 300 mg·kg–1·d–1 for 6 weeks. The measurements included body weight, fasting plasma glucose, glycosylated serum protein(GSP) and serum insulin. Data were analyzed with SPSS 22.0 and Prism 7. The level of statistical significance was set at P<0.05. In single dosing experiments, pharmacokinetic parameters(t1/2, AUC0–t and Cmax) did not differ between Glucophage~? and the generic metformin(P>0.05). However, plasma glucose was significantly higher in the generic metformin group at 2 h(P = 0.03) and 4 h(P = 0.04) after drug treatment. In repeated dosing experiments, fasting glucose, HOMA-IR and body weight in rats receiving high-dose Glucophage~? were significantly lower at the end of the 6-week treatment period than those in rats receiving high-dose generic metformin(P<0.05 for all). GSP and serum insulin did not differ significantly between the two groups. In rats receiving low-dose metformin, fasting glucose was lower in the Glucophage~? group. HOMA-IR and body weight did not differ between the two groups. Moreover, blood lipids did not differ significantly between the two groups. The generic metformin used in the current study did not differ significantly in pharmacokinetic characteristics with Glucophage~?. However, Glucophage~? was superior in terms of glucose control, body weight loss and insulin sensitivity in repeated administration.展开更多
文摘Aim To establish a LC-MS method for determining the concentration of nifedipine in human plasma and to evaluate the pharmacokinetic characteristics of nifedipine sustained-release tablets. Methods A XB-C18 （5 μm, 4.6 mm ×150 mm） column and a mobile phase of methanol： 0.01 mol·L^-1ammonium acetate （60：40, V/V） were used to separate nifedipine, the detections was accuracy under atmosperic pressure electronic spray ionization （AP-ESI） mode and ion mass spectrum （m/z） of 314.9 [M＋H]^＋ for nifedipine, and 320.8 [M＋H]^＋ for lorazepam （Internal Standard, IS）. Results The linear range of nifedipine was 0.3 - 80 ng·mL^-1 （ r = 0.9997）, and the limit of quantitation （LOQ） was 0.3 ng·mL^-1. The nifedipine pharmacokinetic parameters after a single dose of 20 mg nifedipine sustained-release tablets test （T） or reference （R） were as the followings, t1/2 （6.73 ± 2.00） h and （7.04 ± 2.18） h, Tmax （4.28 ± 0.70） h and （4.48 ± 0.70） h, Cmax（39.66 ± 10.58） ng·mL^-1 and （40.19 ± 10.97） ng·mL^-1, AUC0-36 （391.63 ± 108.55） ng·mL^-1·h and （387.57 ± 121.51） ng·mL^-1·h, and AUC0-∞ （408.28 ± 121.16） ng·mL^-1·h and （406.15 ± 133.13） ng·mL^-1·h. The relative bioavailability of nifedipine sustained-release tablets （test） was （103.02 ± 13.93） %. Conclusion LC-MS method for the determination of concentrations of nifedipine in human plasma was sensitive and accurate, and could be used in nifedipine bioavailability and pharmacokinetic studies.
文摘Aim To evaluate the pharmacokinetics and bioequivalence of domestic pantoprazole sodium enteric-coated tablets as compared with imported pantoprazole enteric-coated tablets. Methods This was an open randomized, two periods cross over study on twenty healthy male volunteers. The pantoprazole concentrations in plasma after an oral dose of 40 mg pantoprzaole preparations were determined by a HPLC-UV method. Non-compartmental method was used for the calculation of pharmacokinetic parameters. Logarithm-transformed Cmax and A UC were analyzed by the analysis of variance （ANOVA） with 90% confidence intervals. Results The main pharmacokinetics parameters of domestic pantoprazole sodium enteric-coated tablets and imported pantoprazole sodium enteric-coated tablets were as following： Cmax （3610 ± 956）, （3466 ± 1209） ng·mL^-1, tmax （3.00 ± 0.40）, （3.00 ± 0.46） h, AUC0-t （8140 ± 5065）, （8390 ± 5474） ng·h·mL^-1, AUC0-∞ （8293 ± 5094）, （8625 ± 5606） ng·h·mL^-1, t1/2 （1.61 ± 0.28）, （1.85 ± 0.27） h, respectively. Conclusion Domestic pantoprazole sodium enteric-coated tablets were bioequivalent with the imported pantoprazole sodium enteric-coated tablets.
文摘Aim To develop a rapid, simple, and sensitive high-performance liquid chromatographic (HPLC) method for the determination of cefprozil in human plasma and to study its pharmacokinetics and bioequivalence after 0.5 g oral doses of cefprozil granules and tablets. Methods The blood concentration of cefprozil was analyzed after extracted with 6% trichloroacetic acid, using tinidazole as internal standard (I.S.). A C_ 18 column was used to separate cefprozil with mobile phase of methanol, purified water and glac...
文摘Aim To establish a HPLC method for the determination of bicalutamide plasma concentration and to evaluate the bioequivalence of bicalutamide capsules （test） and tablets （reference）. Methods A single oral dose of 50 mg bicalutamide capsules or tablets were given to 48 Chinese healthy volunteers in a one period parallel design test. Bicalutamide in plasma was analyzed using a XB-C18 column with a mobile phase of acetonitrile-water （60：40, V/V） and the dectection wavelength of 272 nm and it is pharmacokinetic parameters were calculated and evaluated using DAS2.0. Results The linear range of bicalutamide was 10 - 1200 ng·mL^-1. The main pharmacokinetic parameters of the test and reference were as the followings, t1/2 （138.36 ± 32.03） and （146.12 ± 27.04） h, Tmax （17.17 ± 4.65） and （16.92 ± 4.85） h, Cmax（910.83 ± 130.49） and （868.71 ± 115.35） ng·mL^-1 AUC0-672（172437.08 ± 3986.07） and （176842.34 ± 35733.85） ng·mL^-1·h, and AUC0-∞ （179456.55 ± 43127.65） and （185270.39 ± 39688.63） ng·mL^-1·h, respectively. The two-one side t-test analysis showed that the confidence intervals of Crux, A UC0-672 and A UC0-∞ were （98.9% - 100.7%）, （98.8% - 100.6%） and （99.7% - 101.7%）, respectively. Conclusion The relative bioavailability of bicalutamide capsules was 97.51%. The bioequivalence was demonstrated by the two-one side t-test
文摘AIM： To evaluate the bioequivalence of ranitidine and bismuth derived from two compound preparations. METHODS： The bioavailability was measured in 20 healthy male Chinese volunteers following a single oral dose （equivalent to 200 mg of ranitidine and 220 mg of bismuth） of the test or reference products in the fasting state. Then blood samples were collected for 24 h. Plasma concentrations of ranitidine and bismuth were analyzed by high-performance liquid chromatography and inductively coupled plasma-mass spectrometry （ICPMS）, respectively. The non-compartmental method was used for pharmacokinetic analysis. Log-transformed Cmax, AUC（0-t） and AUC（0-∞） were tested for bioequivalence using ANOVA and Schuirmann two-one sided t-test. Tmax was analyzed by Wilcoxon＇s test. RESULTS： Various pharmacokinetic parameters of ranitidine derived from the two compound preparations, including Cmax, AUC（0-t）, AUC（0-∞）, Tmax and T1/2, were nearly consistent with previous observations. These parameters derived from test and reference drug were as follows： Cmax（0.67 ± 0.21 vs 0.68 ± 0.22 mg/L）, AUC（0-t）（3.1 ± 0.6 vs 3.0 ± 0.7 mg/L per hour）, AUC（0-∞）（3.3 ± 0.6 vs 3.2 ± 0.8 mg/L per hour）, Tmax （2.3 ± 0.9 VS 2.1 ± 0.9 h） and T1/2 （2.8 ± 0.3 vs 3.1 ± 0.4 h）. In addition, double-peak absorption profiles of ranitidine were found in some Chinese volunteers. For bismuth, those parameters derived from test and reference drug were as follows： Cmax （11.80 ± 7.36 vs 11.40 ± 6.55 μg/L）, AUC（0-t） （46.65 ± 16.97 vs 47.03 ± 21.49 μg/L per hour）, Tmax （0.50 ± 0.20 vs 0.50 ± 0.20 h） and T1/2 （10.2 ± 2.3 vs 13.0 ± 6.9 h）. Ninety percent of confidence intervals for the test/reference ratio of Cmax, AUC（0-t） and AUC（0-∞） derived from both ranitidine and bismuth were found within the bioequivalence acceptable range of 80%-125%. No significant difference was found in Tmax derived from both ranitidine and bismuth. CONCLUSION： The two compound preparations are bioequivalent and may be prescribed interchangeably.
基金Supported by the National High Technology Research and Development Program of China (863 program) (No. 2007AA091604)the Knowledge Innovation Project of Chinese Academy of Sciences(No. KZCX2-YW-209)
文摘Gelatin has been used in hard capsule shells for more than a century, and some shortcomings have appeared, such as high moisture content and risk of transmitting diseases of animal origin to people. Based on available studies regarding gelatin and vegetable shells, we developed a new type of algal polysaccharide capsule (APPC) shells. To test whether our products can replace commercial gelatin shells, we measured in-vivo plasma concentration of 12 selected volunteers with a model drug, ibuprofen, using high performance liquid chromatography (HPLC), by calculating the relative bioavailability of APPC and Qualicaps referenced to gelatin capsules and assessing bioequivalence of the three types of shells, and calculated pharmacokinetic parameters with the software DAS 2.0 (China). The results show that APPC shells possess bioequivalence with Qualicaps and gelatin shells. Moreover, the disintegration behavior of four types of shells (APPC, Vegcaps , Qualicaps and gelatin shells) with the content of lactose and radioactive element (99mTc) was observed via gamma-scintigraphic images. The bioavailability and gamma-scintigraphic studies showed that APPC was not statistically different from other vegetable and gelatin capsule shells with respect to in-vivo behavior. Hence, it can be concluded that APPCs are exchangeable with other vegetable and gelatin shells.
基金supported by Institute of Clinical Pharmacy,Central South University,Changsha,China
文摘In the present study, we determined the pharmacokinetics and bioequivalence of two amlodipine tablets in Chinese male and female volunteers using HPLC-MS/IVIS method. A randomized, two-period and crossover design was conducted in 20 healthy volunteers （14 male subjects and six female subjects）. A single dose of either the reference or test formulation was given at the start of each period. Blood samples were collected before drug administration and at 1, 2, 3, 4, 5, 6, 8, I0, 12, 24, 48, 72, 96, 120 and 144 h after drug administration. Plasma amlodipine was detected by HPLC-MS/MS method, and the pharmacokinetic parameters were analyzed using DAS 3.2.8. The developed HPLC-MS/MS method was suitable for the analysis of amlodipine in biological matrix samples. The main pharmacokinetic parameters between the trial preparation and the reference preparation met the regulatory criteria for bioequivalence, and the two preparations were both well tolerated.
文摘The clinical pharmacokinetics of osmotic pump controlled release tablets of terazosin hydrochloride in healthy volunteers was studied.A sensitive and rapid HPLC method was used to determine the terazosin plasma concentrations,and single and multiple doses of terazosin hydrochloride regular tablets（reference tablets）and osmotic pump controlled release tablets were orally administrated in randomized crossover design.The results showed that the C_（max）of the reference tablets after single oral dose（（120.56±23.15）ng/mL）in 20 healthy volunteers was significantly higher than that of controlled release tablets （（95.27±16.35）ng/mL）.The T_（max）of the controlled release tablets（（2.65±0.82）h）was significantly longer than that of reference tablets（（1.27±0.61）h）（P0.05）.The relative bioavailability of the controlled release tablets was found to be（105.85±6.12）%. The multiple oral dose pharmacokinetic parameters of the regular tablets and controlled release tablets were as follows：AUC_（SS） were（1275.17±175.35）and（1382.65±205.31）ng·h/mL respectively,C_（max）were（128.15±22.37）and（98.57±18.16）ng/mL respectively,T_（max）were（1.35±0.71）and（2.76±0.85）h respectively,C_（av）were（53.13±9.12）and（57.61±9.25）ng/mL respectively, and DF were（2.25±0.26）%and（1.62±0.25）%respectively.The relative bioavailability of the controlled release tablets to the reference tablets was（108.43±6.26）%.The controlled release tablet of terazosin hydrochloride was bioequivalent to the reference tablet.The controlled release tablet exhibited a sustained-release property with a significantly longer T_（max）and lower C_（max）.
基金The National Key Development Plan for Precision Medicine Research(Grant No.2017YFC0910004)Jinan Science Project(Grant No.201602171)
文摘In the present study, we aimed to compare the pharmacokinetics and pharmacodynamics between Glucophage~? and a generic metformin formulation in a diabetic rat model in order to assess the bioequivalence of the generic formulation. Adult male Zucker diabetes fatty rats received Glucophage~? or the generic metformin through gastric gavage at a dose of 180 mg/kg(n = 6 per condition). Both pharmacokinetic parameters(AUC0–t, AUC0–∞, Cmax) of metformin and plasma glucose levels were compared between the two groups. For pharmacodynamics, rats received Glucophage~? or the generic metformin at doses of 180 and 300 mg·kg–1·d–1 for 6 weeks. The measurements included body weight, fasting plasma glucose, glycosylated serum protein(GSP) and serum insulin. Data were analyzed with SPSS 22.0 and Prism 7. The level of statistical significance was set at P<0.05. In single dosing experiments, pharmacokinetic parameters(t1/2, AUC0–t and Cmax) did not differ between Glucophage~? and the generic metformin(P>0.05). However, plasma glucose was significantly higher in the generic metformin group at 2 h(P = 0.03) and 4 h(P = 0.04) after drug treatment. In repeated dosing experiments, fasting glucose, HOMA-IR and body weight in rats receiving high-dose Glucophage~? were significantly lower at the end of the 6-week treatment period than those in rats receiving high-dose generic metformin(P<0.05 for all). GSP and serum insulin did not differ significantly between the two groups. In rats receiving low-dose metformin, fasting glucose was lower in the Glucophage~? group. HOMA-IR and body weight did not differ between the two groups. Moreover, blood lipids did not differ significantly between the two groups. The generic metformin used in the current study did not differ significantly in pharmacokinetic characteristics with Glucophage~?. However, Glucophage~? was superior in terms of glucose control, body weight loss and insulin sensitivity in repeated administration.
