Objective: To evaluate the antioxidant, immunomodulatory and anti-inflammatory activities of pyrrolidine dithiocarbamate and saxagliptin in rats with thioacetamide-induced ulcerative colitis. Methods: Animals were ora...Objective: To evaluate the antioxidant, immunomodulatory and anti-inflammatory activities of pyrrolidine dithiocarbamate and saxagliptin in rats with thioacetamide-induced ulcerative colitis. Methods: Animals were orally administered with a vehicle, sulfasalazine(500 mg/kg), pyrrolidine dithiocarbamate(100 mg/kg), and saxagliptin(10 mg/kg) for two weeks. Ulcerative colitis was induced by a single intrarectal instillation of thioacetamide on day 8. Colon samples were collected to assess mitogen-activated protein kinase(MAPK), phosphorylated extracellular signal-regulated kinase(ERK), c AMP response element-binding protein(CREB), interleukin-12(IL-12), caspase-3, β-defensin, inducible nitric oxide synthase(i NOS) and glucagon like peptide-1(GLP-1). Moreover, histopathological examination was performed. Results: Rats treated with thioacetamide caused increases in colonic MAPK, phosphorylated ERK, CREB, caspase-3, IL-12, β-defensin, i NOS, as well as decreases in body weight and GLP-1. In addition, distortion of colonic structure was found by histopathological examination. Pyrrolidine dithiocarbamate and saxagliptin mitigated colitis severity by improving body weight decrease and GLP-1, and reducing colonic MAPK, phosphorylated ERK, CREB, caspase-3, IL-12, β-defensin and i NOS. Conclusions: Pyrrolidine dithiocarbamate and saxagliptin are efficient against thioacetamide induced colitis through improving inflammatory and oxidative changes.展开更多
A simple, specific, accurate and precise high performance thin layer chromatographic method (HPTLC) was developed for the quantitative analysis of Saxagliptin in active pharmaceutical ingredients (APIs) and pharmaceut...A simple, specific, accurate and precise high performance thin layer chromatographic method (HPTLC) was developed for the quantitative analysis of Saxagliptin in active pharmaceutical ingredients (APIs) and pharmaceutical dosage forms. The method was achieved using silica gel aluminum plate 60 F254 (10 × 10 cm) as stationary phase and Methanol:Chloroform (6:4 v/v) as mobile phase. The developed plate was scanned densitometrically using UV 222 nm wavelength. The Rf value of Saxagliptin was found to be 0.50 ± 0.02. The developed method was validated according to ICH guidelines. Limit of detection (LOD) and limit of quantification (LOQ) of Saxagliptin by this method were found as 7.96 ng/spot and 26.54 ng/spot, respectively. The method was found to be sensitive, specific, linear, accurate, precise and robust for the quantitative analysis of Saxagliptin in both APIs and marketed tablet formulation.展开更多
A simple, specific, sensitive, precise and accurate reverse phase high performance liquid chromatographic method (RP-HPLC) was developed for the simultaneous analysis of Metformin and Saxagliptin in active pharmaceuti...A simple, specific, sensitive, precise and accurate reverse phase high performance liquid chromatographic method (RP-HPLC) was developed for the simultaneous analysis of Metformin and Saxagliptin in active pharmaceutical ingredients (APIs) as well as in marketed tablet (combination) dosage forms. The method was achieved on Enable C18 G (250 × 4.6 mm;5 μm particle size) column using 0.05 M KH2PO4 buffer (pH 4.5):Methanol:Acetonitrile (60:20:20 %v/v) as a mobile phase at a flow rate of 0.6 mL/min and by employing UV detection at 220 nm wavelength. The retention time of Metformin and Saxagliptin were found to be 4.38 min and 6.92 min, respectively. The method was validated as per ICH guidelines. The limit of detection (LOD) and limit of quantification (LOQ) of Metformin were found to be 0.112 μg/mL and 0.373 μg/mL, respectively, while those of Saxagliptin were found to be 0.029 μg/mL and 0.096 μg/mL, respectively. The method was found to be rapid, sensitive, linear, specific, accurate, precise and economic for the quality control and stability assays of Metformin and Saxagliptin in marketed tablet dosage forms.展开更多
Introduction: Good glycaemic control without causing excessive hypoglycaemia reduced the risk of macrovascular and microvascular complications in type 2 DM patients on regular haemodialysis (HD). The objectives of thi...Introduction: Good glycaemic control without causing excessive hypoglycaemia reduced the risk of macrovascular and microvascular complications in type 2 DM patients on regular haemodialysis (HD). The objectives of this study were to assess the efficacy and safety of add-on saxagliptin to insulin therapy in blood sugar control compared to insulin therapy alone in diabetic patients undergoing HD. Design and Methods: In this prospective open-labelled randomized controlled trial, HD patients with type 2 DM and on stable insulin therapy with HbA1c 7% - 13% were randomized to receive add-on saxagliptin 2.5 mg once daily to insulin therapy or insulin therapy only for 12 weeks. Results: 24 patients were randomized into each arm equally. Baseline and week-12 serum HbA1c, fructosamine, fasting blood glucose (FBS) and mean self monitoring blood glucose (SMBG) were comparable in the groups. Reduction of HbA1c and mean SMBG were significant in both groups. There was a significant drop in fructosamine levels (p = 0.004) and trend of lower FBS (p = 0.097) in add-on saxagliptin group but not in insulin alone group. The incidence of hypoglycaemia was the same in both groups. Conclusion: Add-on saxagliptin to insulin is comparable to insulin therapy alone in blood sugar control in regular HD patients and is safe and generally well tolerated. Add-on saxagliptin group may have more persistent and less fluctuation of glucose control compared to insulin only group.展开更多
As a new oral hypoglycemic agent, saxagliptin belongs to the class of dipeptidyl peptidase-4 （DPP-4） inhibitors. However, it remains inconclusive whether saxagliptin is associated with increased risk of adverse even...As a new oral hypoglycemic agent, saxagliptin belongs to the class of dipeptidyl peptidase-4 （DPP-4） inhibitors. However, it remains inconclusive whether saxagliptin is associated with increased risk of adverse events （AE） and efficacy as add-on treatment. Therefore, we performed an up-to-date meta-analysis to compare the efficacy and safety of saxagliptin with placebo and other oral hypoglycemic agents in adult patients with type 2 diabetes mellitus （T2DM）. Randomized clinical trials （RCTs） comparing saxagliptin with comparators were retrieved by selecting articles from Pubmed, Embase, Cochrane Library and Clinical Trials Registry Platform up to Oct. 2013. Weighted mean difference （WMD） was used to analyze the effect of hypoglycemic agents on HbAlc, weight and fasting plasma glucose （FPG）. While the patients who achieved HbAlc〈7.0% and had AE were analyzed as relative risks （RR）. A total of 18 articles from 16 RCTs and one clinic trial from the WHO International Clinical Trials Registry Platform met the included criterion. Clinically significant decrease from baseline HbAlc compared with placebo was certified for 2.5 mg/day saxagliptin （WMD = -0.45%, 95% CI, -0.48% to -0.42%） and 5 mg/d saxagliptin （WMD = -0.52%, 95% CI, -0.60% to -0.44%）. Saxagliptin as add-on therapy was superior to thiazolidinediones, up-titrated glyburide, up-titrated metformin or metformin monotherapy in achieving HbA1c〈7.0%. Treatment with saxagliptin had negligible effect on weight, and it was considered weight neutral. Saxagliptin treatment did not increase the risk of hypoglycemia （RR = 1.28, 95% CI 0.72 to 2.27, P = 0.40） and serious adverse experiences （RR = 1.25, 95% CI 0.94 to 1.66, P = 0.13）. No statistically significant differences were observed between saxagliptin and comparators in terms of the risk of infections. The present study showed that saxagliptin was effective in improving glycaemic control in T2DM with a low risk of hypoglycaemia and incidence of infections in either monotherapy or add-on treatment. This founding should be further certified by large-sample size and good-designed RCT.展开更多
In this study,we aimed to develop and evaluate a whole-body physiologically based pharmacokinetic(WB-PBPK)/pharmacodynamic(PD)model for saxagliptin,simulate its pharmacokinetic and pharmacodynamic properties in health...In this study,we aimed to develop and evaluate a whole-body physiologically based pharmacokinetic(WB-PBPK)/pharmacodynamic(PD)model for saxagliptin,simulate its pharmacokinetic and pharmacodynamic properties in healthy adults and patients with hepatic function impairment,and provide a new method for the research to the clinical pharmacy of special patients.Based on the drug-specific properties,such as log D,plasma protein binding collected by the published literature,the WB-PBPK model and the PD model were established.After comparing the simulated concentration-time profiles and the pharmacokinetic parameters with data in healthy adults from oral and intravenous clinical investigation,the WB-PBPK model could be optimized.After comparing the simulated DPP-4 inhibition profile with the observed pharmacodynamic in healthy subjects,the PD model could be optimized.The PK/PD model was utilized to predict the mean and variability of the pharmacokinetic and pharmacodynamic profiles in subjects with different hepatic impairment.All of the predicted pharmacokinetic curves were comparable to the observed curves both in healthy subjects and hepatic impairment subjects(Cmax and AUC were less than 1.3-fold).The predicted pharmacodynamic curves were comparable to the observed ones in different oral dosage after optimization,and pharmacodynamics of saxagliptin in hepatic impairment subjects were predicted successfully.The WB-PBPK/PD model can accurately simulate the pharmacokinetics and pharmacodynamics of saxagliptin in normal adults and different hepatic impaired patients.展开更多
目的分析2型糖尿病(Diabetes Mellitus Type 2,T2DM)肥胖型患者采用沙格列汀与利拉鲁肽联合治疗的效果。方法选取2022年9月—2023年8月济南市章丘区中医医院收治的94例T2DM肥胖型患者,按照随机数表法分为研究组和对照组,各47例。研究组...目的分析2型糖尿病(Diabetes Mellitus Type 2,T2DM)肥胖型患者采用沙格列汀与利拉鲁肽联合治疗的效果。方法选取2022年9月—2023年8月济南市章丘区中医医院收治的94例T2DM肥胖型患者,按照随机数表法分为研究组和对照组,各47例。研究组采用沙格列汀与利拉鲁肽联合治疗,对照组仅采用沙格列汀治疗。对比两组血糖值、体质指数(Body Mass Index,BMI)、腰围、胰岛功能指标以及不良反应。结果研究组治疗12周后空腹血糖(7.52±1.50)mmol/L低于对照组(9.56±1.46)mmol/L,差异有统计学意义(t=6.681,P<0.05),研究组餐后2 h血糖、糖化血红蛋白值较对照组低,且胰岛功能优于对照组,差异有统计学意义(P均<0.05)。与治疗12周后的对照组结果对比,研究组的BMI与腰围值更低,差异有统计学意义(P均<0.05)。两组不良反应发生率对比,差异无统计学意义(P>0.05)。结论T2DM肥胖型患者采用沙格列汀与利拉鲁肽联合治疗不仅可以改善血糖值与胰岛功能,且降低了BMI与腰围,安全性较为理想。展开更多
文摘Objective: To evaluate the antioxidant, immunomodulatory and anti-inflammatory activities of pyrrolidine dithiocarbamate and saxagliptin in rats with thioacetamide-induced ulcerative colitis. Methods: Animals were orally administered with a vehicle, sulfasalazine(500 mg/kg), pyrrolidine dithiocarbamate(100 mg/kg), and saxagliptin(10 mg/kg) for two weeks. Ulcerative colitis was induced by a single intrarectal instillation of thioacetamide on day 8. Colon samples were collected to assess mitogen-activated protein kinase(MAPK), phosphorylated extracellular signal-regulated kinase(ERK), c AMP response element-binding protein(CREB), interleukin-12(IL-12), caspase-3, β-defensin, inducible nitric oxide synthase(i NOS) and glucagon like peptide-1(GLP-1). Moreover, histopathological examination was performed. Results: Rats treated with thioacetamide caused increases in colonic MAPK, phosphorylated ERK, CREB, caspase-3, IL-12, β-defensin, i NOS, as well as decreases in body weight and GLP-1. In addition, distortion of colonic structure was found by histopathological examination. Pyrrolidine dithiocarbamate and saxagliptin mitigated colitis severity by improving body weight decrease and GLP-1, and reducing colonic MAPK, phosphorylated ERK, CREB, caspase-3, IL-12, β-defensin and i NOS. Conclusions: Pyrrolidine dithiocarbamate and saxagliptin are efficient against thioacetamide induced colitis through improving inflammatory and oxidative changes.
文摘A simple, specific, accurate and precise high performance thin layer chromatographic method (HPTLC) was developed for the quantitative analysis of Saxagliptin in active pharmaceutical ingredients (APIs) and pharmaceutical dosage forms. The method was achieved using silica gel aluminum plate 60 F254 (10 × 10 cm) as stationary phase and Methanol:Chloroform (6:4 v/v) as mobile phase. The developed plate was scanned densitometrically using UV 222 nm wavelength. The Rf value of Saxagliptin was found to be 0.50 ± 0.02. The developed method was validated according to ICH guidelines. Limit of detection (LOD) and limit of quantification (LOQ) of Saxagliptin by this method were found as 7.96 ng/spot and 26.54 ng/spot, respectively. The method was found to be sensitive, specific, linear, accurate, precise and robust for the quantitative analysis of Saxagliptin in both APIs and marketed tablet formulation.
文摘A simple, specific, sensitive, precise and accurate reverse phase high performance liquid chromatographic method (RP-HPLC) was developed for the simultaneous analysis of Metformin and Saxagliptin in active pharmaceutical ingredients (APIs) as well as in marketed tablet (combination) dosage forms. The method was achieved on Enable C18 G (250 × 4.6 mm;5 μm particle size) column using 0.05 M KH2PO4 buffer (pH 4.5):Methanol:Acetonitrile (60:20:20 %v/v) as a mobile phase at a flow rate of 0.6 mL/min and by employing UV detection at 220 nm wavelength. The retention time of Metformin and Saxagliptin were found to be 4.38 min and 6.92 min, respectively. The method was validated as per ICH guidelines. The limit of detection (LOD) and limit of quantification (LOQ) of Metformin were found to be 0.112 μg/mL and 0.373 μg/mL, respectively, while those of Saxagliptin were found to be 0.029 μg/mL and 0.096 μg/mL, respectively. The method was found to be rapid, sensitive, linear, specific, accurate, precise and economic for the quality control and stability assays of Metformin and Saxagliptin in marketed tablet dosage forms.
文摘Introduction: Good glycaemic control without causing excessive hypoglycaemia reduced the risk of macrovascular and microvascular complications in type 2 DM patients on regular haemodialysis (HD). The objectives of this study were to assess the efficacy and safety of add-on saxagliptin to insulin therapy in blood sugar control compared to insulin therapy alone in diabetic patients undergoing HD. Design and Methods: In this prospective open-labelled randomized controlled trial, HD patients with type 2 DM and on stable insulin therapy with HbA1c 7% - 13% were randomized to receive add-on saxagliptin 2.5 mg once daily to insulin therapy or insulin therapy only for 12 weeks. Results: 24 patients were randomized into each arm equally. Baseline and week-12 serum HbA1c, fructosamine, fasting blood glucose (FBS) and mean self monitoring blood glucose (SMBG) were comparable in the groups. Reduction of HbA1c and mean SMBG were significant in both groups. There was a significant drop in fructosamine levels (p = 0.004) and trend of lower FBS (p = 0.097) in add-on saxagliptin group but not in insulin alone group. The incidence of hypoglycaemia was the same in both groups. Conclusion: Add-on saxagliptin to insulin is comparable to insulin therapy alone in blood sugar control in regular HD patients and is safe and generally well tolerated. Add-on saxagliptin group may have more persistent and less fluctuation of glucose control compared to insulin only group.
基金Xinjiang Medical University Scientific Research and Innovation Foundation(Grant No.XYDCX2014117)
文摘As a new oral hypoglycemic agent, saxagliptin belongs to the class of dipeptidyl peptidase-4 （DPP-4） inhibitors. However, it remains inconclusive whether saxagliptin is associated with increased risk of adverse events （AE） and efficacy as add-on treatment. Therefore, we performed an up-to-date meta-analysis to compare the efficacy and safety of saxagliptin with placebo and other oral hypoglycemic agents in adult patients with type 2 diabetes mellitus （T2DM）. Randomized clinical trials （RCTs） comparing saxagliptin with comparators were retrieved by selecting articles from Pubmed, Embase, Cochrane Library and Clinical Trials Registry Platform up to Oct. 2013. Weighted mean difference （WMD） was used to analyze the effect of hypoglycemic agents on HbAlc, weight and fasting plasma glucose （FPG）. While the patients who achieved HbAlc〈7.0% and had AE were analyzed as relative risks （RR）. A total of 18 articles from 16 RCTs and one clinic trial from the WHO International Clinical Trials Registry Platform met the included criterion. Clinically significant decrease from baseline HbAlc compared with placebo was certified for 2.5 mg/day saxagliptin （WMD = -0.45%, 95% CI, -0.48% to -0.42%） and 5 mg/d saxagliptin （WMD = -0.52%, 95% CI, -0.60% to -0.44%）. Saxagliptin as add-on therapy was superior to thiazolidinediones, up-titrated glyburide, up-titrated metformin or metformin monotherapy in achieving HbA1c〈7.0%. Treatment with saxagliptin had negligible effect on weight, and it was considered weight neutral. Saxagliptin treatment did not increase the risk of hypoglycemia （RR = 1.28, 95% CI 0.72 to 2.27, P = 0.40） and serious adverse experiences （RR = 1.25, 95% CI 0.94 to 1.66, P = 0.13）. No statistically significant differences were observed between saxagliptin and comparators in terms of the risk of infections. The present study showed that saxagliptin was effective in improving glycaemic control in T2DM with a low risk of hypoglycaemia and incidence of infections in either monotherapy or add-on treatment. This founding should be further certified by large-sample size and good-designed RCT.
文摘In this study,we aimed to develop and evaluate a whole-body physiologically based pharmacokinetic(WB-PBPK)/pharmacodynamic(PD)model for saxagliptin,simulate its pharmacokinetic and pharmacodynamic properties in healthy adults and patients with hepatic function impairment,and provide a new method for the research to the clinical pharmacy of special patients.Based on the drug-specific properties,such as log D,plasma protein binding collected by the published literature,the WB-PBPK model and the PD model were established.After comparing the simulated concentration-time profiles and the pharmacokinetic parameters with data in healthy adults from oral and intravenous clinical investigation,the WB-PBPK model could be optimized.After comparing the simulated DPP-4 inhibition profile with the observed pharmacodynamic in healthy subjects,the PD model could be optimized.The PK/PD model was utilized to predict the mean and variability of the pharmacokinetic and pharmacodynamic profiles in subjects with different hepatic impairment.All of the predicted pharmacokinetic curves were comparable to the observed curves both in healthy subjects and hepatic impairment subjects(Cmax and AUC were less than 1.3-fold).The predicted pharmacodynamic curves were comparable to the observed ones in different oral dosage after optimization,and pharmacodynamics of saxagliptin in hepatic impairment subjects were predicted successfully.The WB-PBPK/PD model can accurately simulate the pharmacokinetics and pharmacodynamics of saxagliptin in normal adults and different hepatic impaired patients.
文摘目的分析2型糖尿病(Diabetes Mellitus Type 2,T2DM)肥胖型患者采用沙格列汀与利拉鲁肽联合治疗的效果。方法选取2022年9月—2023年8月济南市章丘区中医医院收治的94例T2DM肥胖型患者,按照随机数表法分为研究组和对照组,各47例。研究组采用沙格列汀与利拉鲁肽联合治疗,对照组仅采用沙格列汀治疗。对比两组血糖值、体质指数(Body Mass Index,BMI)、腰围、胰岛功能指标以及不良反应。结果研究组治疗12周后空腹血糖(7.52±1.50)mmol/L低于对照组(9.56±1.46)mmol/L,差异有统计学意义(t=6.681,P<0.05),研究组餐后2 h血糖、糖化血红蛋白值较对照组低,且胰岛功能优于对照组,差异有统计学意义(P均<0.05)。与治疗12周后的对照组结果对比,研究组的BMI与腰围值更低,差异有统计学意义(P均<0.05)。两组不良反应发生率对比,差异无统计学意义(P>0.05)。结论T2DM肥胖型患者采用沙格列汀与利拉鲁肽联合治疗不仅可以改善血糖值与胰岛功能,且降低了BMI与腰围,安全性较为理想。
