Sample records for gliclazide

  1. Fabrication and Characterization of Gliclazide Loaded Microcapsules

    Muhammad Asad


    Full Text Available This study aimed to formulate, characterize and evaluate the Gliclazide (GLZ microcapsules prepared with sodium alginate, guar gum and pectin in different ratios by ionotropic-gelation method. The microcapsules were evaluated against different parameters such as particle size and shape, Carr's index, Hausner's ratio, rheological studies and drug release kinetics. Fourier Transform Infra Red (FTIR and Differential Scanning Calorimetric (DSC studies demonstrated the absence of any drug - polymers interaction. Promising characteristics were observed in rheological behavior and release kinetics. The size of microcapsules and percentage yield was in the range of 676 to 727 µm and 69 to 77%, respectively. Scanning electron micrographs revealed that microcapsules were discrete, spherical and free flowing. Entrapment efficiency and uniform drug release kinetics were some of the probable characteristics depicting the novel formulation design of Gliclazide microcapsules.

  2. Is gliclazide a sulfonylurea with difference? A review in 2016.

    Singh, Awadhesh Kumar; Singh, Ritu


    Sulfonylureas (SUs) remain the most commonly prescribed drug after metformin in the treatment of type 2 diabetes (T2DM), despite the availability of several newer agents. The primary reason of SUs being most popular is their quick glycemic response, time-tested experience and least cost. Although SUs are one amongst the several other second line agents after metformin in all major guidelines, the new Dutch type 2 guidelines specifically advise gliclazide as the preferred second line drug instead of SUs as a class. The World Health Organization (WHO) has also included gliclazide in their Model List of Essential Medicines 2013 motivated by its safety data in elderly patients. Specifically advising gliclazide may have been based on emerging evidence suggesting cardiovascular neutrality of gliclazide over other SUs. This prompted us to do a literature review of gliclazide efficacy and safety data compared to other SUs as well as oral anti-diabetic drugs.

  3. [The use of gliclazide in individualized sulfonylurea therapy].

    Winkler, Gábor


    In addition to the common blood glucose lowering effect, sulfonylurea compounds are different in many aspects from each other. Based on earlier findings the second generation gliclazide has special advantages within this group. Although the number of experimental and clinical observations on gliclazide is continuously increasing, these novel findings are not in the focus anymore due to the appearance of new antidiabetics. This article reviews recent experimental (effect on receptors, the absence of Epac2 activation, antioxidant properties, possible incentive of factors participating in beta-cell differentiation) and pharmacogenomic data, and compares them with clinical observations obtained from gliclazide treatment (hypoglycemias, parameters of cardiovascular outcome). The data underline the advantages of gliclazide, the highly pancreas-selective nature, preservation of the ischemic precondition, favourable hemodynamic properties and potential reduction of the beta-cell loss as compared to other compounds of the group. However, gliclazide is not free from disadvantages characteristic to sulfonylureas in general (blood glucose independent insulin stimulation, beta-cell depletion). Comparing gliclazide with other derivatives of the group, the above data indicate individual benefits for the application when sulfonylurea compound is the drug of choice.


    Thakkar Hardik Kumar Rajeshbhai


    Full Text Available A gastro retentive floating drug delivery system containing gliclazide was prepared in the form of tablet and evaluated for its processing parameters and in vitro release behaviour. Gliclazide is a selective second-generation sulphonyl urea used in treatment of hyperglycemia and it absorbs rapidly and completely. However its absorption is erratic in diabetic patient due to its impaired gastric motility or gastric emptying. To overcome these drawbacks, the present investigation was to develop a gastro retentive floating tablets of gliclazide. Ten formulations containing retardant materials such as hydroxypropylmethylcellulose K4M and K15M, sodium bicarbonate was used as a gas generating agent to reduce floating lag time and other release promoters. Tablets remained buoyant over 12 hours in the release medium, and the amount of sodium bicarbonate found to be significant for not only to remaining buoyant without causing disintegration of the tablet, but also to release of the drug in the acidic medium. Final F6 optimized formulation released approximately 99% drug in 12 hours in vitro, while the floating lag time was 39 sec and tablet remained floatable throughout all studies. In vitro gastro retentive study of tablets gave successful results by floating in gastric content over a period of 24 hours. The results of the current study clearly indicate, a promising potential of the gliclazide floating system as an alternative to the conventional dosage form.

  5. Design and evaluation of transdermal drug delivery system of gliclazide

    Shinde Anilkumar; Shinde Amit; More Harinath


    Transdermal systems are ideally suited for diseases that demand chronic treatment. Hence, an anti-diabetic agent of both therapeutic and prophylactic usage has been subjected to transdermal investigation. Gliclazide, a second-generation hypoglycemic agent, faces problems like its poor solubility, poor oral bioavailability with large individual variation and extensive metabolism. In the present work, transdermal matrix-type patches were prepared by film casting techniques on mercury using poly...


    Shardendu Prakash


    Full Text Available The objective of the present study was to develop floating microspheres of Gliclazide in order to achieve an extended retention in the upper gastrointestinal tract, which may result in enhanced absorption and thereby improved bioavailability. The present study involves preparation and evaluation of floating microspheres using Gliclazide as a model drug for prolongation of the gastric retention time. As gliclazide is mainly absorbed from stomach, thus using floating microspheres as a mode of drug delivery helps in increasing its residence time and hence increasing the bioavailability of drug. The microspheres were prepared by the Ionic gelation method. The average diameter and surface morphology of the prepared microspheres were characterized by optical microscope and scanning electron microscopic methods respectively. The prepared microspheres were evaluated for particle size, micromeritic study, drug entrapment efficiency, in vitro buoyancy, swelling index and in vitro release. The effect of various formulation variables on the size and drug release was also investigated. All the formulated microspheres were found to possess good flow properties. Scanning electron microscopy confirmed spherical structure of the prepared microspheres. The best formulation F3 drug release kinetics were evaluated using Zero order, First order, Higuchi model, Korsmeyer - Peppas model. After the interpretation of data that was based on the value of a resulting regression coefficient, it was observed that the Korsmeyer- Peppas model has a highest regression coefficient values indicating that the drug release was based on the erosion of polymeric chain matrix.


    Meka, Venkata Srikanth; Yee, Phung; Sheshala, Ravi


    In the past few years, there are number of researchers carrying out their research on the excipients derived from polysaccharides and some of these researches show that natural excipients are comparable and can serve as an alternative to the synthetic excipients. Hence, the objectives of this research are to characterize the naturally sourced chickpea starch powder and to study the pharmaceutical excipient behavior of chickpea starch in gliclazide immediate release (IR) tablets. In this research, the binding properties of chickpea starch were compared to that of povidone, whereas the disintegrant properties of chickpea starch were compared to those of crospovidone, croscarmellose sodium and sodium starch glycolate. Flow property of chickpea starch was assessed with the measurement of bulk density, tapped density, compressibility index and angle of repose. Calibration curve for gliclazide in phosphate buffer pH 7.4 was developed. Gliclazide IR tablets were then produced with direct compression method. Physicochemical characteristics of the tablets, including thickness, tablet weight uniformity, hardness, disintegration time and friability were evaluated. Then, in vitro dissolution studies were performed by following United States Pharmacopeia (USP) dissolution method. The dissolution results were analyzed and compared with t30, t50, dissolution efficiency (DE). Lastly, drug-excipient compatibility studies, including Fourier transform infrared (FTIR) spectroscopic analysis and differential scanning calorimetric (DSC) analysis were carried out. Fair flow property was observed in the chickpea starch powder. Furthermore, the tablets produced passed all the tests in physicochemical characteristics evaluation except hardness and disintegration test. Additionally, in vitro dissolution studies show that chickpea starch acted as a disintegrant instead of a binder in gliclazide IR tablets and its disintegrant properties were comparable to those of crospovidone, croscarmellose

  8. Design and evaluation of transdermal drug delivery system of gliclazide

    Shinde Anilkumar


    Full Text Available Transdermal systems are ideally suited for diseases that demand chronic treatment. Hence, an anti-diabetic agent of both therapeutic and prophylactic usage has been subjected to transdermal investigation. Gliclazide, a second-generation hypoglycemic agent, faces problems like its poor solubility, poor oral bioavailability with large individual variation and extensive metabolism. In the present work, transdermal matrix-type patches were prepared by film casting techniques on mercury using polymers like HPMC, Eudragit RL-100, and chitosan. Also an attempt was made to increase the permeation rate of drug by preparing an inclusion complex with hydroxypropyl β-cyclodextrin (HP β-CD. The possibility of a synergistic effect of chemical penetration enhancers (CPE (propylene glycol and oleic acid on the transdermal transport of the drug was also studied. Folding endurance was found to be high in patches containing higher amount of the Eudragit. There was increase in tensile strength with an increase in Eudragit in the polymer blend. In vitro drug release profile indicates that the drug release is sustained with increasing the amount of Eudragit in patches. The patches containing inclusion complex of drug showed higher permeation flux compared with patches containing plain drug. The result of the synergistic effect indicates that the HP β- CD in conjunction with other CPE showed a higher permeation flux.

  9. Waist Circumference-dependent Peripheral Monocytes Change after Gliclazide Treatment for Chinese Type 2 Diabetic Patients

    Qing LI; Hao-yong YU; Miao CHEN; Feng JIANG; Jian ZHOU; Yu-qian BAO; Cheng HU; Wei-ping JIA


    Gliclazide used for the treatment of type 2 diabetes mellitus (T2DM) stimulates insulin secretion and influences peripheral blood monocytes.The roles of gliclazide in peripheral monocytes of newly diagnosed T2DM patients were investigated in this study.A total of 105 newly diagnosed T2DM patients with no history of antihyperglycemic medication were treated with gliclazide-modified release for 16 weeks.The total and differential leukocyte profiles of peripheral blood were measured at baseline and week 16.The peripheral blood monocyte count at week 16 was significantly lower than that at baseline (P=0.019).Peripheral monocytes level at baseline was positively correlated with waist circumference.After gliclazide treatment,the peripheral monocytes were decreased [(320.09±15.13)×106/L vs.(294.19±14.22)×106/L] in non-abdominal obesity group,but increased in abdominal obesity group [(344.36±17.24)×106/L vs.(351.87±16.93)×106/L].Compared with non-abdominal obese patients,abdominal obese patients showed higher Amonocytes (P=0.046) and Aacute insulin secretion (P=0.049),but lower AHbAlc (P=0.047).There was significantly positive correlation between Amonocytes and Aacute insulin secretion (P=0.015),which disappeared after adjusting for age,waist circumference and dosage at baseline.In conclusion,waist circumference is correlated with peripheral monocyte change after gliclazide treatment in Chinese newly diagnosed T2DM patients.Peripheral monocytes are decreased in non-abdominal obesity group and increased in abdominal obesity group after gliclazide treatment.

  10. Drug-drug Interaction between Pravastatin and Gemfibrozil (Antihyperlipidemic) with Gliclazide (Antidiabetic) in Rats.

    Sultanpur, Cm; Satyanarayana, S; Reddy, Ns; Kumar, Ke; Kumar, S


    Diabetes mellitus is a condition of increased blood glucose level in the body. Antihyperlipidemic drugs like statins and fibrates are widely used for prophylactic treatment in dyslipideamia and atherosclerosis. Diabetic dislipidemia exists with increased triglycerides, low HDL and high LDL levels. Hence, with oral hypoglycemic drugs, the addition of a lipid-lowering drug is necessary for controlling dislipidemia. In such a situation, there may be chances of drug-drug interactions between antidiabetic and antihyperlipidemic drugs. The present study is planned to evaluate the safety of gliclazide (antidiabetic) in the presence of pravastatin and gemfibrozil (antihyperlpidemic) in rats. Studies in normal and alloxan-induced diabetic rats were conducted with oral doses of gliclazide and their combination with pravastatin and gemfibrozil, with an adequate washout period in between the treatments. Blood samples were collected in rats by retroorbital puncture at 0, 1, 2, 3, 4, 6, 8, 10 and 12 h. All the blood samples were analyzed for glucose by GOD -POD. Gliclazide (½ TD) produced hypoglycemic activity in normal and diabetic rats, with peak activity at 2 and 8 h. Pravastatin (TD) + gemfibrozil (TD) combination treatment increased the hypoglycemic effect of gliclazide in normal rats or diabetic rats when administered together. The interaction observed due to inhibition of both the enzymes (CYP 450 2C9 and CYP 450 3A4) responsible for the metabolism of gliclazide showed increased half-life, which was seen in the present study. Because concomitant administration of gliclazide with provastatin and gemfibrozil in diabetes is associated with atherosclerosis, it should be contraindicated or used with caution.

  11. Drug–drug Interaction between Pravastatin and Gemfibrozil (Antihyperlipidemic) with Gliclazide (Antidiabetic) in Rats

    Sultanpur, CM; Satyanarayana, S; Reddy, NS; Kumar, KE; Kumar, S


    Diabetes mellitus is a condition of increased blood glucose level in the body. Antihyperlipidemic drugs like statins and fibrates are widely used for prophylactic treatment in dyslipideamia and atherosclerosis. Diabetic dislipidemia exists with increased triglycerides, low HDL and high LDL levels. Hence, with oral hypoglycemic drugs, the addition of a lipid-lowering drug is necessary for controlling dislipidemia. In such a situation, there may be chances of drug–drug interactions between antidiabetic and antihyperlipidemic drugs. The present study is planned to evaluate the safety of gliclazide (antidiabetic) in the presence of pravastatin and gemfibrozil (antihyperlpidemic) in rats. Studies in normal and alloxan-induced diabetic rats were conducted with oral doses of gliclazide and their combination with pravastatin and gemfibrozil, with an adequate washout period in between the treatments. Blood samples were collected in rats by retroorbital puncture at 0, 1, 2, 3, 4, 6, 8, 10 and 12 h. All the blood samples were analyzed for glucose by GOD –POD. Gliclazide (½ TD) produced hypoglycemic activity in normal and diabetic rats, with peak activity at 2 and 8 h. Pravastatin (TD) + gemfibrozil (TD) combination treatment increased the hypoglycemic effect of gliclazide in normal rats or diabetic rats when administered together. The interaction observed due to inhibition of both the enzymes (CYP 450 2C9 and CYP 450 3A4) responsible for the metabolism of gliclazide showed increased half-life, which was seen in the present study. Because concomitant administration of gliclazide with provastatin and gemfibrozil in diabetes is associated with atherosclerosis, it should be contraindicated or used with caution. PMID:21264118

  12. Gliclazide mainly affects insulin secretion in second phase of type 2 diabetes mellitus

    Ligtenberg, JJM; van Haeften, TW


    We studied the effect of the acute administration of gliclazide at 160 mg on insulin release during hyperglycaemic clamps in 12 type 2 diabetes patients, age 50 +/- 9.0 years, diabetes duration 55 +/- 4.8 years, fasting blood glucose 9.6 +/- 2.1 mmol/L (means +/- SD). After a 210 min of hyperinsulin

  13. Using resonance light scattering and UV/vis absorption spectroscopy to study the interaction between gliclazide and bovine serum albumin.

    Zhang, Qiu-Ju; Liu, Bao-Sheng; Li, Gai-Xia; Han, Rong


    At different temperatures (298, 310 and 318 K), the interaction between gliclazide and bovine serum albumin (BSA) was investigated using fluorescence quenching spectroscopy, resonance light scattering spectroscopy and UV/vis absorption spectroscopy. The first method studied changes in the fluorescence of BSA on addition of gliclazide, and the latter two methods studied the spectral change in gliclazide while BSA was being added. The results indicated that the quenching mechanism between BSA and gliclazide was static. The binding constant (Ka ), number of binding sites (n), thermodynamic parameters, binding forces and Hill's coefficient were calculated at three temperatures. Values for the binding constant obtained using resonance light scattering and UV/vis absorption spectroscopy were much greater than those obtained from fluorescence quenching spectroscopy, indicating that methods monitoring gliclazide were more accurate and reasonable. In addition, the results suggest that other residues are involved in the reaction and the mode 'point to surface' existed in the interaction between BSA and gliclazide. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  14. Development of modified release gliclazide biological macromolecules using natural biodegradable polymers.

    Prajapati, Vipulkumar D; Mashru, Krupa H; Solanki, Himanshu K; Jani, Girish K


    Modified release biological macromolecules (beads) of gliclazide using sodium alginate combined with either gellan gum or pectin in different ratios were prepared by Ionotropic gelation method. Biological macromolecules were evaluated for different physico-chemical parameters. Increase in polymers proportion showed difficulty in production of biological macromolecules due to high viscosity of dispersion. As the polymer concentration increases, the swelling and entrapment efficiency of drug increased. Compared to all other batches and commercial modified release gliclazide tablet, formulated biological macromolecules of sodium alginate with pectin (2:1 ratio) and with gellan gum (6:0.75 ratio) exhibited spherical shape, biphasic in vitro release profile and initial high drug release followed by moderate release up to 12 h as matrix diffusion kinetics and Higuchi model as well as Korsmeyer model. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. Studies on influence of process variables on performance of gliclazide mucoadhesive microcapsules

    Bala Vishnu Priya Mukkala


    Full Text Available Microencapsulation is a unique technique of controlled drug delivery system and is of major importance for effective alteration of drug release required to produce a novel formulation with desired characteristics to overcome the disadvantages of the conventional therapeutic dosage forms. Microcapsules offer efficient absorption and enhanced bioavailability owing to their higher surface area, however, mucoadhesive microcapsules render more intimate contact with the mucus membrane thereby leading to increase in the gastro intestinal residence time. Gliclazide is an oral hypoglycemic second generation sulfonyl urea, which is useful for a long-term treatment of non-insulin dependent diabetes mellitus. In the present investigation, the gliclazide microcapsules are formulated to control the release rate and improve the absorption across gastrointestinal membrane by employing ionic gelation method. The effect of various process variables such as curing time, stirring speed, stirring time, volume and concentration of curing reagent on entrapment efficiency, and drug release rate was studied. The microcapsules were evaluated for drug content, encapsulation efficiency, in vitro drug release studies. The optimized formulation was selected based on the entrapment efficiency and drug release rate. The optimized formulation of gliclazide microcapsules were evaluated for rheological properties, moisture content, swelling index, erosion studies, wall thickness and in vitro wash off test. The microcapsules formulated with 2:1 coat:core ratio by using 150 ml of 0.1M Cacl2 solution as curing reagent, at a stirring speed of 400 rpm for 60 minutes and a curing period of 48 hrs were found to be the optimum formulation. The drug release followed zero order kinetics and was controlled by peppas mechanism. The pharmacodynamic activity of optimized gliclazide microcapsules was conducted by measuring blood glucose levels in healthy albino rabbits. The percentage glucose

  16. Limited sampling strategy models for estimating the AUC of gliclazide in Chinese healthy volunteers.

    Huang, Ji-Han; Wang, Kun; Huang, Xiao-Hui; He, Ying-Chun; Li, Lu-Jin; Sheng, Yu-Cheng; Yang, Juan; Zheng, Qing-Shan


    The aim of this work is to reduce the cost of required sampling for the estimation of the area under the gliclazide plasma concentration versus time curve within 60 h (AUC0-60t ). The limited sampling strategy (LSS) models were established and validated by the multiple regression model within 4 or fewer gliclazide concentration values. Absolute prediction error (APE), root of mean square error (RMSE) and visual prediction check were used as criterion. The results of Jack-Knife validation showed that 10 (25.0 %) of the 40 LSS based on the regression analysis were not within an APE of 15 % using one concentration-time point. 90.2, 91.5 and 92.4 % of the 40 LSS models were capable of prediction using 2, 3 and 4 points, respectively. Limited sampling strategies were developed and validated for estimating AUC0-60t of gliclazide. This study indicates that the implementation of an 80 mg dosage regimen enabled accurate predictions of AUC0-60t by the LSS model. This study shows that 12, 6, 4, 2 h after administration are the key sampling times. The combination of (12, 2 h), (12, 8, 2 h) or (12, 8, 4, 2 h) can be chosen as sampling hours for predicting AUC0-60t in practical application according to requirement.

  17. Novel tamarind seed polysaccharide-alginate mucoadhesive microspheres for oral gliclazide delivery: in vitro-in vivo evaluation.

    Pal, Dilipkumar; Nayak, Amit Kumar


    Novel tamarind seed polysaccharide (TSP)-alginate mucoadhesive microspheres were prepared using TSP and alginate as blend in different ratios with different calcium chloride (CaCl(2)) concentration as a cross linker by ionotropic gelation. The prepared microspheres were of spherical shape having rough surfaces, and average particle sizes within the range of 752.12 ± 6.42 to 948.49 ± 20.92 µm. The drug entrapment efficiency of these microspheres were within the range between 58.12 ± 2.42 to 82.78 ± 3.43% w/w. Fourier transform infrared (FTIR) studies indicated that there were no reactions between gliclazide, and polymers (TSP, and sodium alginate) used. Different formulations of gliclazide loaded TSP-alginate microspheres showed prolonged in vitro release profiles of gliclazide over 12 hours in both stomach pH (pH 1.2), and intestinal pH (pH 7.4). It was found that the gliclazide release in gastric pH was comparatively slow and sustained than intestinal pH. These TSP-alginate microspheres also exhibited good mucoadhesivity. The in vivo studies on alloxan-induced diabetic rats (Animal Ethical Committee registration number: IFTM/837ac/0160) demonstrated the significant hypoglycemic effect of selected formulation of TSP-alginate mucoadhesive microspheres containing gliclazide on oral administration. This developed gliclazide loaded new TSP-alginate mucoadhesive microspheres may be very much useful for prolonged systemic absorption of gliclazide for proper maintaining blood glucose level and advanced patient compliance.

  18. Association between TCF7L2 Genotype and Glycemic Control in Diabetic Patients Treated with Gliclazide

    Martin Javorský


    Full Text Available Previous studies showed associations between variants in TCF7L2 gene and the therapeutic response to sulfonylureas. All sulfonylureas stimulate insulin secretion by the closure of ATP-sensitive potassium (KATP channel. The aim of the present study was to compare TCF7L2 genotype specific effect of gliclazide binding to KATP channel A-site (Group 1 with sulfonylureas binding to AB-site (Group 2. A total of 101 patients were treated with sulfonylureas for 6 months as an add-on therapy to the previous metformin treatment. TCF7L2 rs7903146 C/T genotype was identified by real-time PCR with subsequent melting curve analysis. Analyses using the dominant genetic model showed significantly higher effect of gliclazide in the CC genotype group in comparison with combined CT + TT genotype group (1.32±0.15% versus 0.73±0.11%, Padj=0.005. No significant difference in ΔHbA1c between the patients with CC genotype and the T-allele carriers was observed in Group 2. In the multivariate analysis, only the TCF7L2 genotype (P=0.006 and the baseline HbA1c (P<0.001 were significant predictors of ΔHbA1c. After introducing an interaction term between the TCF7L2 genotype and the sulfonylurea type into multivariate model, the interaction became a significant predictor (P=0.023 of ΔHbA1c. The results indicate significantly higher difference in ΔHbA1c among the TCF7L2 genotypes in patients treated with gliclazide than in patients treated with glimepiride, glibenclamide, or glipizide.

  19. Dissolution enhancement of gliclazide by preparation of inclusion complexes with β-cyclodextrin

    Hiremath S


    Full Text Available Gliclazide is an oral hypoglycemic agent used in the treatment of non-insulin-dependent diabetes mellitus. The drug is practically insoluble in water and exhibits an exceedingly slow intrinsic dissolution rate and poor bioavailability. The present study has emphasized on improving the solubility and dissolution rate of the drug by forming inclusion complex with β -cyclodextrin. Phase solubility studies indicated the formation of 1:2 M complex in solution. The value of apparent stability constant K c was found to be 691.45 M -1 . The inclusion complexes were prepared by physical mixture and kneading method. Prepared complexes were characterized by infrared (IR spectroscopy and differential scanning calorimetry (DSC studies, which indicated formation of 1:2 M complex. The gliclazide:β -CD (1:2 M complex prepared by kneading method exhibited higher dissolution rate and dissolution efficiency values in 0.1-N HCl. A 20.31-fold increase in dissolution rate and 16.50-fold increase in dissolution efficiency values were observed in the kneading method.

  20. A Supercritical Fluid Chromatography/Tandem Mass Spectrometry Method for the Simultaneous Quantification of Metformin and Gliclazide in Human Plasma

    Agrawal, Y. K.; Gogoi, P. J.; Manna, K.; Bhatt, H. G.; Jain, V. K.


    Present study reports the development and validation of a simultaneous estimation of metformin and gliclazide in human plasma using supercritical fluid chromatography followed by tandem mass spectrometry. Acetonitrile:water (80:20) mixture was used as a mobile phase along with liquid CO2 in supercritical fluid chromatography and phenformin as an internal standard. The modified plasma samples were analyzed by electro-spray ionization method in selective reaction monitoring mode in tandem mass spectrometry. Supercritical fluid chromatographic separation was performed using nucleosil C18 containing column as a stationary phase. The separated products were identified by characteristic peaks and specific fragments peaks in tandem mass spectrometry as m/z 130 to 86 for metformin, m/z 324 to 110 for gliclazide and m/z 206 to 105 for phenformin. The present method was found linear in the concentration ranges of 6.0-3550 ng/ml and 7.5-7500 ng/ml for metformin and gliclazide, respectively. Pharmacokinetic study was performed after an oral administration of dispersible tablets containing 500 mg of metformin and 80 mg of gliclazide using same techniques. PMID:20582190

  1. Characterization of gliclazide-polyethylene glycol solid dispersion and its effect on dissolution

    Moreshwar Pandharinath Patil


    Full Text Available The present study was initiated with the objective of studying the in vitro dissolution behavior of gliclazide from its solid dispersion with polyethylene glycol 6000. In this work, a solid dispersion of gliclazide with polyethylene glycol was prepared by the fusion method. In vitro dissolution study of gliclazide, its physical mixture and solid dispersion were carried out to demonstrate the effect of PEG 6000. Analytical techniques of FT-IR spectroscopy, differential scanning calorimetry and X-ray diffractometry were used to characterize the drug in the physical mixtures and solid dispersions. The dissolution studies of solid dispersion and physical mixture showed greater improvement compared to that of the pure drug. The mechanisms for increased dissolution rate may include reduction of crystallite size, a solubilization effect of the carrier, absence of aggregation of drug crystallites, improved wettability and dispersbility of the drug from the dispersion, dissolution of the drug in the hydrophilic carrier or conversion of drug to an amorphous state. The FT-IR spectra suggested that there was no interaction between gliclazide and PEG 6000 when prepared as a solid dispersion. DSC and XRD study indicated that the drug was converted in the amorphous form.O presente trabalho foi realizado com o objetivo de estudar o comportamento in vitro da dissolução da gliclazida a partir da sua dispersão sólida com polietileno glicol 6000. Neste trabalho, as dispersões sólidas de gliclazida com polietileno glicol foram preparadas pelo método de fusão. Os estudo de dissolução in vitro da gliclazida, na mistura física e nas dispersões sólidas foram realizados para demonstrar o efeito de PEG 6000. Técnicas analíticas como espectroscopia FT-IR, calorimetria diferencial de varredura e difração de raios-X foram empregadas para caracterizar o fármaco nas misturas físicas e nas dispersoes sólidas. Os estudos de dissolução demonstraram maior

  2. Probiotics decreased the bioavailability of the bile acid analog, monoketocholic acid, when coadministered with gliclazide, in healthy but not diabetic rats.

    Al-Salami, Hani; Butt, Grant; Tucker, Ian; Golocorbin-Kon, Svetlana; Mikov, Momir


    In recent studies we showed that gliclazide has no hypoglycemic effect on type 1 diabetic (T1D) rats while MKC does, and their combination exerted a better hypoglycemic effect than MKC alone. We also showed that the most hypoglycemic effect was noticed when T1D rats were treated with probiotics then gavaged with MKC + gliclazide (blood glucose decreased from 24 ± 3 to 10 ± 2 mmol/l). The aim of this study is to investigate the influence of probiotics on MKC pharmacokinetics when coadministered with gliclazide, in T1D rats. 80 male Wistar rats (weight 350 ± 50 g) were randomly allocated into 8 groups (10 rats/group), 4 of which were injected with alloxan (30 mg/kg) to induce T1D. Group 1 was healthy and group 2 was diabetic. Groups 3 (healthy) and 4 (diabetic) were gavaged with probiotics (75 mg/kg) every 12 h for 3 days and 12 h later all groups received a single oral dose of MKC + gliclazide (4 and 20 mg/kg respectively). The remaining 4 groups were treated in the same way but administered MKC + gliclazide via the i.v. route. Blood samples collected from T1D rats prior to MKC + gliclazide revealed that probiotic treatment alone reduced blood glucose levels twofold. When coadministered with gliclazide, the bioavailability of MKC was reduced in healthy rats treated with probiotics but remained the same in diabetic pretreated rats. The decrease in MKC bioavailability, when administered with gliclazide, caused by probiotic treatment in healthy but not diabetic rats suggests that probiotic treatment induced MKC metabolism or impaired its absorption, only in healthy animals. The different MKC bioavailability in healthy and diabetic rats could be explained by different induction of presystemic elimination of MKC in the gut by probiotic treatment.

  3. Novel artificial cell microencapsulation of a complex gliclazide-deoxycholic bile acid formulation: a characterization study

    Mooranian A


    Full Text Available Armin Mooranian,1 Rebecca Negrulj,1 Nigel Chen-Tan,2 Hesham S Al-Sallami,3 Zhongxiang Fang,4 Trilochan Mukkur,5 Momir Mikov,6,7 Svetlana Golocorbin-Kon,6,7 Marc Fakhoury,8 Frank Arfuso,5 Hani Al-Salami1 1Biotechnology and Drug Development Research Laboratory, School of Pharmacy, Curtin Health Innovation Research Institute, Biosciences Research Precinct, Curtin University, Perth, WA, Australia; 2Faculty of Science and Engineering, Curtin University, Perth, WA, Australia; 3School of Pharmacy, University of Otago, Dunedin, New Zealand; 4School of Public Health, Curtin University, Perth, WA, Australia; 5Curtin Health Innovation Research Institute, Biosciences Research Precinct, School of Biomedical Science, Curtin University, Perth, WA, Australia; 6Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia; 7Department of Pharmacy, Faculty of Medicine, University of Montenegro, Podgorica, Montenegro; 8Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada Abstract: Gliclazide (G is an antidiabetic drug commonly used in type 2 diabetes. It has extrapancreatic hypoglycemic effects, which makes it a good candidate in type 1 diabetes (T1D. In previous studies, we have shown that a gliclazide-bile acid mixture exerted a hypoglycemic effect in a rat model of T1D. We have also shown that a gliclazide-deoxycholic acid (G-DCA mixture resulted in better G permeation in vivo, but did not produce a hypoglycemic effect. In this study, we aimed to develop a novel microencapsulated formulation of G-DCA with uniform structure, which has the potential to enhance G pharmacokinetic and pharmacodynamic effects in our rat model of T1D. We also aimed to examine the effect that DCA will have when formulated with our new G microcapsules, in terms of morphology, structure, and excipients' compatibility. Microencapsulation was carried out using the Büchi-based microencapsulating system

  4. Development of novel gastroretentive floating particulate drug delivery system of gliclazide.

    Awasthi, Rajendra; Kulkarni, Giriraj T


    The objective of present project was to improve the dissolution profile of gliclazide by developing floating alginate beads using various biodegradable polymers like gelatin, pectin and hydroxypropylmethylcellulose (HPMC). The floating beads were prepared by a simple ionotropic gelatin method using calcium carbonate as gas generating agent. The developed beads were characterized by Fourier transform infrared spectroscopy analysis, differential scanning calorimetry, X-ray diffraction analysis and scanning electron microscopy (SEM). The prepared beads showed good in vitro floatation, which was dependent on the concentration of gas-forming agent. SEM photomicrographs confirmed that the developed beads were spherical in shape and had particle size in the range of 730 to 890 μm. The incorporation efficiency was found to be in the range of 59.96 to 85.1%. The cumulative percent drug release from the beads after 10 h dissolution study at pH 1.2 and pH 5.8 was in the range of 33 to 46% and 82 to 95% respectively. The concentration of the gas generating agent was found to influence the release rate. The mechanism of drug release was Fickian diffusion with swelling. The in vivo sub-acute hypoglycemic study in high fat diet induced diabetic C57BL/6J mice demonstrated significant (p < 0.05) hypoglycemic effect over a period of 12 h and 24 h, respectively, with HPMC and pectin beads. A significant (p & 0.05) reduction in fasting and non-fasting blood glucose levels, reduction in fasting plasma insulin level and a significant improvement in glucose tolerance were observed in animals treated with formulations. The developed beads were suitable carriers for improving the systemic absorption of gliclazide and maintaining reduced blood glucose levels.


    Teraiya Sandip R


    Full Text Available The aim of this study was to demonstrate that the asymmetric membrane capsule can be used to deliver apoorly water soluble drug with a pH sensitive solubility such as gliclazide. In order to obtain the desireddelivery duration, the drug was solubilized with the use of a pH-controlling excipient. The capsule wallmembrane was made by a phase inversion process, in which asymmetric membrane was formed on glassmold pins by dipping the mold pins into a coating solution containing a polymeric material followed bydipping into a quench solution. This study evaluates the influence of coating formulation that wascellulose acetate (CA, ethyl cellulose (EC, and plasticizer (glycerin and PEG 600. Results showcapsule that made by CA with glycerol and PEG 600(F8, which appear in asymmetric structure and areable to release gliclazide(GLZ in significant percentage. Results show that sodium bicarbonate and Dmannitolis able to promote the release of GLZ from polymeric capsules prepared with CA withasymmetrical membrane. The addition of solubilizer, sodium lauryl sulphate (SLS could enhance therelease of GLZ by micelle formation of GLZ. Based on these results, influence of core formulationvariables, including D-mannitol, sodium bicarbonate and the added amount of SLS were examined onthe release of GLZ. It was found that HPMC 15cp was suitable to be a thickening agent and both addedamount of HPMC and SLS showed a comparable and profoundly positive effect. In vitro release studiesfor all the prepared formulations were done (n=3. Statistical test (Dunnett’s multiple comparison testwas applied for in vitro drug release at P>0.05. The best formulation closely corresponded to themarketed formulation by a similarity (f2 value of 78.36 and difference (f1 value of 4.49. The drugrelease was independent of pH but dependent on the osmotic pressure of the dissolution medium. Therelease kinetics followed the First order model and the mechanism of release was anomalous type.

  6. Safety and efficacy of gliclazide as treatment for type 2 diabetes: a systematic review and meta-analysis of randomized trials.

    Gijs W D Landman

    Full Text Available OBJECTIVE AND DESIGN: Gliclazide has been associated with a low risk of hypoglycemic episodes and beneficial long-term cardiovascular safety in observational cohorts. The aim of this study was to assess in a systematic review and meta-analysis of randomized controlled trials the safety and efficacy of gliclazide compared to other oral glucose-lowering agents (PROSPERO2013:CRD42013004156. DATA SOURCES: Medline, EMBASE,,, and the Cochrane database. SELECTION: Included were randomized studies of at least 12 weeks duration with the following outcomes: HbA1c change, incidence of severe hypoglycemia, weight change, cardiovascular events and/or mortality when comparing gliclazide with other oral blood glucose lowering drugs. Bias was assessed with the Cochrane risk of bias tool. The inverse variance random effects model was used. RESULTS: Nineteen trials were included; 3,083 patients treated with gliclazide and 3,155 patients treated with other oral blood glucose lowering drugs. There was a considerable amount of heterogeneity between and bias in studies. Compared to other glucose lowering agents except metformin, gliclazide was slightly more effective (-0.13% (95%CI: -0.25, -0.02, I(2 55%. One out of 2,387 gliclazide users experienced a severe hypoglycemic event, whilst also using insulin. There were 25 confirmed non-severe hypoglycemic events (2.2% in 1,152 gliclazide users and 22 events (1.8% in 1,163 patients in the comparator group (risk ratio 1.09 (95% CI: 0.20, 5.78, I² 77%. Few studies reported differences in weight and none were designed to evaluate cardiovascular outcomes. CONCLUSIONS: The methodological quality of randomized trials comparing gliclazide to other oral glucose lowering agents was poor and effect estimates on weight were limited by publication bias. The number of severe hypoglycemic episodes was extremely low, and gliclazide appears at least equally effective

  7. Influence of the semisynthetic bile acid MKC on the ileal permeation of gliclazide in vitro in healthy and diabetic rats treated with probiotics.

    Al-Salami, H; Butt, G; Tucker, I; Mikov, M


    The aim of this study was to investigate the influence of sodium 3alpha,7alpha-dihydroxy-12-keto-5beta-cholanate (MKC) on the ileal permeation of gliclazide in healthy and diabetic rats treated with probiotics. Male Wistar rats (2-3 months, 350 +/- 50 g) were randomly allocated into four groups (n = 32); Groups 1 and 2 were healthy controls and Groups 3 and 4 were diabetic rats (alloxan 30 mg/kg was administered i.v.), which were administered probiotics for three days after the rats became diabetics. The rats were sacrificed and tissues were mounted on Ussing chambers. Then, gliclazide (200 microg/ml) was added to all the groups, while MKC (50 microg/ml) was given to Groups 2 and 4, for the measurement of the mucosal to serosal absorption Jss(MtoS) and serosal to mucosal secretion Jss(StoM) of gliclazide. In the tissues of healthy rats treated with probiotics, MKC stimulated the net absorption of gliclazide by stimulating the absorptive and reducing the secretory unidirectional fluxes, while in tissues from diabetic rats treated with probiotics, MKC had no effect. In healthy rats treated with probiotics, the degradation of MKC by bacterial polypeptides produced divalent bile salts that inhibited Mrp2, which resulted in reducing secretion and stimulating the absorption of gliclazide. In contrast, in diabetic rats treated with probiotics, MKC had no effect possibly due to a difference in the metabolic profile and resulting in no net flux.

  8. Spectroscopic and Thermal Characterization of Gliclazide, Glibenclamide and Glimeperide Complexes with Transition and Inner Transition Metals



    Full Text Available Metal complxes of Gliclazide, Glibenclamide and Glimeperide drugs were prepared and characterized based on elemental analysis, FT-IR, Molar conductance and thermal analysis (TGA and DTG technique. From elemental analysis data, the complexes were proposed to have general formulae (GLZ2Co2H2O, (GLZ2Cu, (GLB2Co2H2O, Cu(GLB 2, (GLM 2Hg and (GLM 2La2H2O. The molar conductance data reveal that all the metal complexes are non-electrolytic, IR spectra shows that GLZ, GLB and GLM are coordinated to metal ions in a neutral bidentate manner from the ESR spectra and XRD-spectra. It is found that the geometrical structures of these complexes are tetrahedral Cu(II ,Hg(II and octrahedral Co(II, La(II. The thermal behavior of these complexes studied using thermogravimetric analysis (TGA and DTG techniques. The results obtained shows that the hydrated complexes lose water molecules of hydration followed immediately by decomposition of the anions and ligand molecules in the successive unseparate steps. Thermogravimetric analysis was carried out to study the decomposition and various kinetic parameters. Freeman Carroll and Sharp Wentworth method have been applied for calculation of kinetic parameters. While data from freeman Carroll method have been used to determine various thermodynamic parameters such as order of reactions, energy of activation, frequency factor, entropy change, free energy change and apparent entropy change and order of reaction..



    Objective To compare the influence of different sulfonylureas on the myocardial protection effect of ischemic preconditioning (IPC) in isolated rat hearts, and ATP-sensitive potassium channel current (IKATP ) of rat ventricular myocytes.Methods Isolated Langendorff perfused rat hearts were randomly assigned to five groups: ( 1 ) control group, (2)IPC group, (3) IPC + glibenclamide (GLB, 10 μmol/L) group, (4) IPC + glimepiride (GLM, 10 μmol/L) group,(5) IPC + gliclazide ( GLC, 50 μmol/L ) group. IPC was defined as 3 cycles of 5 -minute zero-flow global ischemia followed by 5-minute reperfusion. The haemodynamic parameters and the infarct size of each isolated heart were recorded.And the sarcolemmal IKATP of dissociated ventricular myocytes reperfused with 10 μmol/L GLB, 1 μmol/L GLM, and 1μmol/L GLC was recorded with single-pipette whole-cell voltage clamp under simulated ischemic condition.Results The infarct sizes of rat hearts in IPC (23.7% ± 1.3% ), IPC + GLM (24. 6% ± 1.0% ), and IPC +GLC (33. 1% ±1.3% ) groups were all significantly smaller than that in control group (43.3% ±1.8%; P <0. 01, n=6). The infarct size of rat hearts in IPC + GLB group (40.4% ± 1.4% ) was significantly larger than that in IPC group (P <0. 01, n =6). Under simulated ischemic condition, GLB ( 10 μmol/L) decreased IKATP from 20. 65 ± 7.80 to 9. 09 ± 0. 10 pA/pF (P < 0. 01, n = 6), GLM ( 1 μ mol/L) did not significantly inhibit IKATP ( n = 6 ), and GLC ( 1μmol/L) decreased IKATP from 16.73 ± 0. 97 to 11.18 ± 3.56 pA/pF ( P < 0. 05, n = 6).Conclusions GLM has less effect on myocardial protection of IPC than GLB and GLC. Blockage of sarcolemmal ATP-sensitive potassium channels in myocardium might play an important role in diminishing IPC-induced protection of GLM, GLB, and GLC.

  10. Gliclazide and bedtime insulin are more efficient than insulin alone for type 2 diabetic patients with sulfonylurea secondary failure

    Chazan A.C.S.


    Full Text Available To determine the effects of combined therapy of gliclazide and bedtime insulin on glycemic control and C-peptide secretion, we studied 25 patients with type 2 diabetes and sulfonylurea secondary failure, aged 56.8 ± 8.3 years, with a duration of diabetes of 10.6 ± 6.6 years, fasting plasma glucose of 277.3 ± 64.6 mg/dl and a body mass index of 27.4 ± 4.8 kg/m². Patients were submitted to three therapeutic regimens lasting 2 months each: 320 mg gliclazide (phase 1, 320 mg gliclazide and bedtime NPH insulin (phase 2, and insulin (phase 3. At the end of each period, glycemic and C-peptide curves in response to a mixed meal were determined. During combined therapy, there was a decrease in all glycemic curve values (P<0.01. Twelve patients (48% reached fasting plasma glucose <140 mg/dl with a significant weight gain of 64.8 kg (43.1-98.8 vs 66.7 kg (42.8-101.4 (P<0.05, with no increase in C-peptide secretion or decrease in HbA1. C-Peptide glucose score (C-peptide/glucose x 100 increased from 0.9 (0.2-2.1 to 1.3 (0.2-4.7 during combined therapy (P<0.01. Despite a 50% increase in insulin doses in phase 3 (12 U (9-30 vs 18 U (11-60; P<0.01 only 3 patients who responded to combined therapy maintained fasting plasma glucose <140 mg/dl (P<0.02. A tendency to a higher absolute increase in C-peptide (0.99 (0.15-2.5 vs 0.6 (0-2.15; P = 0.08 and C-peptide incremental area (2.47 (0.22-6.2 vs 1.2 (0-3.35; P = 0.07 was observed among responders. We conclude that combined therapy resulted in a better glucose response to a mixed meal than insulin alone and should be tried in type 2 diabetic patients before starting insulin monotherapy, despite difficulties in predicting the response.

  11. Bioequivalence between two commercial formulations of gliclazide in Colombia Bioequivalencia entre dos formulaciones comerciales de gliclazida en Colombia

    Ignacio Rodríguez


    Full Text Available Two commercial formulations of Gliclazide 80 mg tablets were studied in order to evaluate both pharmaceutical and biological equivalence, Glidiab® Tecnoquímicas Laboratories and Diamicron® Euroetika-Elsevier Laboratories. After proving the pharmaceutical equivalence, a bioequivalence was tested in 14 healthy volunteers and the determination of gliclazide in plasma was carried out by high-performance liquid chromatography (HPLC. The evaluated pharmacokinetic parameters were: area under the curve (AUC from 0 to 60 hours, maximum concentration (Cmax and time to maximum concentration (Tmax. In statistical analysis the 90.0% confidence intervals for AUC, Cmax and Tmax, and acceptance range for bioequivalence of 80.0%-125.0% to AUC and Cmax and acceptance range of 80:0%-120.0% to Tmax, were applied. Both formulations presented inter and intra subject high variability and it was found that they are bioequivalent in relation to AUC but they are not bioequivalent in relation to Cmax and Tmax. Los formulaciones comerciales de Gliclazida de 80 mg – tabletas, los productos Glidiab® de Tecnoquímicas y Diamicron® de Euroetika-Elsevier, fueron sometidos a estudio para evaluar la equivalencia farmacéutica y la equivalencia biológica. Después de comprobar la equivalencia farmacéutica se llevó a cabo el estudio de la equivalencia biológica en 14 voluntarios sanos; la cuantificación de Gliclazida en plasma se realizó por la técnica de cromatografía líquida de alta resolución (HPLC. Los parámetros farmacocinéticos evaluados fueron: área bajo la curva (AUC de 0-60 horas, concentración máxima (Cmáx y el tiempo máximo (tmáx los cuales se analizaron estadísticamente con intervalos de confianza del 90.0% y un rango de aceptación para bioequivalencia del 80.0% al 125.0% para AUC y Cmáx y del 80.0% al 120.0% para el tmáx. Ambas formulaciones presentaron alta variabilidad inter e intrasujeto y se encontró que son bioequivalentes con

  12. A double-blind, randomized trial, including frequent patient–physician contacts and Ramadan-focused advice, assessing vildagliptin and gliclazide in patients with type 2 diabetes fasting during Ramadan: the STEADFAST study

    Hassanein M


    Full Text Available Mohamed Hassanein,1 Khalifa Abdallah,2 Anja Schweizer31Betsi Cadwaladr University Health Board, Wales, United Kingdom; 2Clinical Research Center, Alexandria University Hospital, Alexandria, Egypt; 3Global Medical Affairs, Novartis Pharma AG, Basel, SwitzerlandBackground: Several observational studies were conducted with vildagliptin in patients with type 2 diabetes mellitus (T2DM fasting during Ramadan, showing significantly lower incidences of hypoglycemia with vildagliptin versus sulfonylureas, including gliclazide. It was of interest to complement the existing real-life evidence with data from a randomized, double-blind, clinical trial.Clinical Trials Identifier: NCT01758380.Methods: This multiregional, double-blind study randomized 557 patients with T2DM (mean glycated hemoglobin [HbA1c], 6.9%, previously treated with metformin and any sulfonylurea to receive either vildagliptin (50 mg twice daily or gliclazide plus metformin. The study included four office visits (three pre-Ramadan and multiple telephone contacts, as well as Ramadan-focused advice. Hypoglycemic events were assessed during Ramadan; HbA1c and weight were analyzed before and after Ramadan.Results: The proportion of patients reporting confirmed (<3.9 mmol/L and/or severe hypoglycemic events during Ramadan was 3.0% with vildagliptin and 7.0% with gliclazide (P=0.039; one-sided test, and this was 6.0% and 8.7%, respectively, for any hypoglycemic events (P=0.173. The adjusted mean change pre- to post-Ramadan in HbA1c was 0.05%±0.04% with vildagliptin and -0.03%±0.04% with gliclazide, from baselines of 6.84% and 6.79%, respectively (P=0.165. In both groups, the adjusted mean decrease in weight was -1.1±0.2 kg (P=0.987. Overall safety was similar between the treatments.Conclusion: In line with the results from previous observational studies, vildagliptin was shown in this interventional study to be an effective, safe, and well-tolerated treatment in patients with T2DM fasting

  13. Hypoglycemia and coma associated with gliclazide and glipizide%格列齐特、格列吡嗪相关低血糖及昏迷

    于栋伟; 顾琴华


    A 69-year-old woman with type 2 diabetes suddenly developed slurred speech and mouth distortion and then was hospitalized. Before admission, the patient received gliclazide 80 mg twice daily and aspirin 0. 1 g once daily. A blood glucose test showed a glucose level of 1. 7 mmol/L. An Ⅳ injection of 50% glucose 100 ml was administered. One hour later, her blood glucose level increased to 20 mmol/L, and her symptoms relieved. Gliclazide was discontinued and replaced with 1 tablet of sustained-release glipizide 5 mg once daily. The next day, her fasting blood glucose level was 1. 7 mmol/L and her postprandial blood glucose level was 2. 7 mmol/L. She also had palpitation, dizziness, and so on. Her symptoms improved after receiving an Ⅳ infusion of 10% glucose 250 ml. On days 3-5 of admission, the hypoglycemic agent was withdrawn, her blood glucose levels were then maintained between 8. 2 mmol/L(fasting) and 10. 1 mmol/L ( postprandial). On day 6, 1 tablet of sustained-release glipizide 5 mg once daily was readministered. Her blood glucose level was maintained within 5. 5-6. 5 mmol/L. Two days later, she was discharged and continued taking sustained-release glipizide tablets. On day 12 after discharge , the patient suddenly redeveloped unconsciousness and no response to verbal stimuli, and then she was readmitted. A blood glucose test showed a glucose level of 1. 6 mmol/L. On day 3 of admission,she started received metformin therapy, and her 2-hour postprandial blood glucose level was maintained at approximately 8. 7 mmol/L.On day 9, she was discharged.%1例69岁女性2型糖尿病患者因突发言语不清和口角歪斜入院.入院前服用格列齐特80 mg,2次/d和阿司匹林0.1 g,1;L/d.查血糖:1.7 mmol/L.给予50%葡萄糖100 ml静脉注射.1 h后血糖升至20 mmol/L,症状缓解.停用格列齐特,改为格列吡嗪缓释片5 mg,1次/d.次日,患者空腹血糖1.7 mmol/L、餐后血糖2.7 mmoL/L,并有心慌、头晕等症状.静脉滴注10%

  14. 格列吡嗪和格列奇特对MIN6细胞的影响%Effects of glipizide and gliclazide on MIN6 cells

    刘继红; 苏青


    Objective: To explore the effects of different sulphonylureas on pancreatic beta-cells. Methods: M1N6 cells were cultured in DMFM and managed with different concentrations of glipizide and gliclazide, and cell viability was detected by MTT. Dihydroethidium ( 11E ) ,2 ,7-dichlo-rofluorescein diacetate ( DCF11-DA ) or dihydrorhodamine 123 ( D11R123 ) was used as reactive oxygen species ( ROS ) capture. The mean fluorescent intensity of ethidium ,2',7'-dichlorofluorescein or rhoda-mine 123, product of intracellular oxidation by the above probes, was detected by fluorescent microscopy and flow cytometry. Cell apoptosis was analyzed by Annexin-V-FITC. Results: In glipizide treated M1N6 cells, cell viability was inhibited and intracellular fluorescent intensity and cell apoptosis were markedly elevated in a dose-and time-dependent fashion( P 0.05);细胞内的MFI无明显增加;细胞凋亡率亦无明显增加.结论:格列吡嗪可诱导MIN6细胞发生氧化应激,诱导MIN6细胞凋亡,说明临床上磺脲类药物治疗糖尿病出现失效可能与磺脲类药物诱发胰岛细胞衰竭相关,然而,格列奇特不诱导MIN6细胞损害,说明并非所有磺脲类药物对β细胞都有损害作用.

  15. Pharmacokinetics of gliclazide osmotic pump tablets in Beagle dogs%格列齐特渗透泵片在Beagle犬体内的药动学

    高国义; 刘志东; 解江纯


    目的 建立格列齐特血药浓度的高效液相色谱测定方法,研究Beagle犬单、多剂量口服格列齐特渗透泵片的药动学.方法 用HPLC法测定6只健康Beagle犬单剂量和多剂量口服格列齐特缓释片和渗透泵片的血药浓度,以DAS 2.0软件计算药动学参数.结果 格列齐特的药一时曲线符合单室模型.单剂量给药后,缓释片和渗透泵片的t1/2分别为(6.0±s 1.6)h和(7.4±2.3)h,tmax分别为(8.0±2.5)h和(6.2±2.9)h,pmax分别为(8.1±3.2)mg·L-1和(6.6±1.6)mg·L-1,AUC0-∞分别为(146±8)mg·h·L-1和(144±17)mg·h·L-1,渗透泵片的相对生物利用度为(99±15)%.多剂量给药后,缓释片和渗透泵片的t1/2分别为(8.0±2.5)h和(9±3)h,tmax分别为(4.2±0.4)h和(5.3±0.5)h,pmax分别为(14.4±1.8)mg·L-1和(12.5±1.7)mg·L-1,pmax分别为(4.1±1.5)mg·L-1和(5.8±1.5)mg·L-1,pav分别为(10.2±1.1)mg·L-1和(11.0±1.2)mg·L-1,AUC0-∞分别为(263±29)mg·h·L-1和(270±31)mg·h·L-1,DF分别为(103±21)%和(61±26)%.渗透泵片的相对生物利用度为(103±9)%.结论 本方法准确、灵敏,格列齐特在犬体内的药动学符合单室模型,2种片剂生物等效.%AIM To establish a method of HPLC for studying the pharmacokinetics of gliclazide osmotic pump tablets after a single and multiple oral administrations in Beagle dogs. METHODS To determine the plasma concentrations of sustained-release tablets and osmotic pump tablets after a single and multiple oral administration in Beagle dogs by HPLC. The pharmacokinetic parameters were calculated with DAS 2.0 software.RESULTS The drug concentration-time curves fitted to a one-compartment model. The pharmacokinetic parameters for the single oral administration of the sustained-release tablets and osmotic pump tablets were t1/2 (6.0 ± s 1.6) h and (7.4 ± 2.3) h, tmax(8.0 ± 2.5) h and (6.2 ± 2.9) h, pmax,(8.1 ± 3.2) mg·L-1 and (6.6 ± 1.6) mg·L-1, AUC(0-∞) (146 ± 8) mg·h·L-1 and (144 ±17) mg·h·L-1, respectively. The

  16. 近红外特征谱段相关系数法测定胶囊中非法添加格列齐特和氢氯噻嗪%Near Infrared Correlation Coefficient Method with Characteristic Spectral Band for Determination of Illegally Added Gliclazide and Hydrochlorothiazide in Capsule Preparations



    Objective To detect the illegally added gliclazide and hydrochlorothiazide in capsule preparations with the near infrared (NIR) correlation coefficient method. Methods The near infrared spectrum of the chemical reference substance of gliclazide and hydrochlorothiazide was used as reference spectrum, the specific spectrum was selected. According to the added amount of gliclazide and hydrochlorothiazide in capsule preparations, the threshold value of similarity coefficient in this spectral band of the tested sample spectrum and the reference spectrum was established. Whether the tested sample contained gliclazide or hydrochlorothiazide was qualitatively estimated. Results The spectral band 5 850~5 700 cm-1 was selected as the characteristic band for gliclazide, and the threshold value was set as 60%. The spectral band 6 150~5 950 cm-1 was selected as the characteristic band for hydrochlorothiazide, and the threshold value was set as 70%. Conclusion The two models have high accuracy and strong applicability, which may be used as a fast detection method to determine illegally added gliclazide and hydrochlorothiazide in traditional Chinese medicine and health food capsule preparations on market.%目的:利用近红外特征谱段相关系数法检测胶囊中是否非法添加格列齐特和氢氯噻嗪。方法以格列齐特和氢氯噻嗪化学对照品的近红外光谱为参照光谱,选择特征谱段,根据格列齐特和氢氯噻嗪被掺入胶囊中的量建立待测样品光谱和参照光谱在该谱段的相似系数阈值,定性判断胶囊中是否含有格列齐特或氢氯噻嗪。结果选定5850~5700 cm-1谱段为格列齐特的特征谱段,设定阈值为60%;选定6150~5950 cm-1谱段为氢氯噻嗪的特征谱段,设定阈值为70%。结论两个模型均有较高的准确性和较强的适用性,可作为检测市售中成药和保健品胶囊剂中非法添加格列齐特和氢氯噻嗪的快检方法。

  17. The mushroom Agaricus Blazei Murill in combination with metformin and gliclazide improves insulin resistance in type 2 diabetes: a randomized, double-blinded, and placebo-controlled clinical trial.

    Hsu, Chung-Hua; Liao, Yang-Li; Lin, Su-Ching; Hwang, Kung-Chang; Chou, Pesus


    Complementary and alternative medicine use in adults with type 2 diabetes is popular. Although most of the herbs and supplements appear to be safe, there is still insufficient evidence that demonstrates their definitive beneficial effects. This study was done to determine whether the supplement of Agaricus blazei Murill extract improves insulin resistance in type 2 diabetes. This study was a clinical randomized, double-blind, placebo-controlled trial. Of a population of 536 registered diabetes patients with 72 subjects (1) aged between 20 and 75 years, (2) being Chinese, (3) having type 2 diabetes for more than 1 year, and (4) having been taking gliclazide and metformin for more than 6 months were enrolled in this study. The enrolled patients were randomly assigned to either receiving supplement of Agaricus blazei Murill (ABM) extract or placebo (cellulose) 1500 mg daily for 12 weeks. Homeostasis model assessment for insulin resistance (HOMA-IR) was used as the major outcome measurement. At the end of the study, subjects who received supplement of ABM extract (n = 29) showed significantly lower HOMA-IR index (3.6[standard deviation, 2.5] versus 6.6[standard deviation, 7.4], p = 0.04) than the control group (n = 31). The plasma adiponectin concentration increased 20.0(standard deviation, 40.7)% in the ABM group after 12 weeks of treatment, but decreased 12.0(20.0)% among those taking the placebo (p diabetes. The increase in adiponectin concentration after taking AMB extract for 12 weeks might be the mechanism that brings the beneficial effect. Studies with longer periods of follow-up should be conducted in the future.

  18. 地特胰岛素联合格列齐特缓释片与诺和锐30治疗2型糖尿病的疗效比较%Comparison of therapeutic effects between insulin detemir combined with gliclazide sustained-release tablets and insulin aspart30 in treating type 2 diabetes melitus

    薛萌; 周宇


      目的比较地特胰岛素联合格列齐特缓释片与诺和锐30治疗2型糖尿病患者的疗效。方法选择80例继发性磺脲类降糖药失效的2型糖尿病患者,随机分为地特胰岛素联合格列齐特缓释片组和诺和锐30治疗组。观察两组治疗前后血糖及HbA1c变化,以及低血糖发生率。结果两组各监测点血糖及HbA1c治疗后与治疗前比较均明显下降(P0.05)。结论地特胰岛素联合格列齐特缓释片与诺和锐30均能有效控制血糖,两组低血糖发生率低且相近。%Objective To study the therapeutic effects of insulin detemir combined with gliclazide sustained-release tablets and insulin aspart30 in treating type 2 diabetes melitus. Methods 80 type 2 diabetes patients with secondary failure to sulfonylureas(SFS) were grouped randomly by insulin detemir combined with gliclazide sustained-release tablets ,insulin aspart30 for 3 months. The blood glucose and HbA1c before and after treatment were observed. And the incidence of hypoglycemia were compared. Result There were statisticaly significant differences in blood glucose at various points in 24 hours and in HbA1c between the two groups before and after treatment (P0.05) .Conclusion The above two treatments can reduce the blood glucose and HbA1c effectively. The incidence of hypoglycemia in insulin detemir combined with gliclazide sustained-release tablets was as low as in insulin aspart30.

  19. 格列齐特对2型糖尿病大鼠肾脏组织中HIF-1α和VEGF表达的影响%Effects of gliclazide on the HIF-1αand VEGF expression in kidney tissue of type 2 diabetic rats

    操轩; 胡亚琳


    Objective:To investigate the effects of gliclazide on the kidney function ,pathology and hypoxia inducible factor-1α( HIF-1α) and vascular en-dothelial growth factor ( VEGF) expression in type 2 diabetic rats induced by high fat diet.Methods:Forty-eight male SD rats were randomly divided into control group ( CG) ,model group ( MG) and gliclazide group ( GG) ( n=16 for each) ,Rats in MG and GG groups were given high fat diet for six months to induce type 2 diabetic models.The eligible animals in GG group were intragastrically administered with gliclazide in dose of 24 mg/( kg・ d) ,and the other two with saline as placebo.By the 6th week and 12th week after treatment,half of rats in each group were sacrificed to obtain the serum and kidney tissues for examination.Results:Renal tissue sections in the CG group remained distinct with no inflammatory reaction.Although the renal tissues in MG group demonstrated significant inflammation,yet it was managed and improved after 6 and 12 weeks of treatment,respectively.The index suggestive of renal function,including blood urea nitrogen,serum creatinine and blood urea was significantly reduced in GG group by the 6th week,further decrease occurred by the 12th week(P<0.05).Expression of HIF-1α,VEGF protein and mRNA in the renal tissues was significantly lower in GG group than MG group af-ter six week of treatment,and the expression was further down-regulated by the 12th week(P<0.05).Conclusion:Gliclazide may inhibit the expression of HIF-1αand VEGF and improve kidney function of type 2 diabetic rats induced by high fat diet.%目的:探讨分析格列齐特对2型糖尿病大鼠肾功能、肾脏病理学、缺氧诱导因子-1α( hypoxia Inducible factor-1α,HIF-1α)及血管内皮生长因子( vascular endothelial growth factor,VEGF)影响。方法:48只雄性SD大鼠,随机分为空白组( control group,CG),模型组( model group,MG)以及格列齐特组( gliclazide group

  20. Pharmacokinetics and bioavailability of two kinds of gliclazide sustained release tablets following a single and multiple dose in healthy volunteers%格列齐特2种缓释片单次和多次给药的药动学和生物利用度比较

    邹健军; 肖大伟; 朱余兵; 莫陵; 于翠霞; 顾荣; 胡云芳; 钱薇; 娄晟


    目的:比较国产和进口格列齐特缓释片的人体药动学和相对生物利用度.方法:采用单次和多次给药的4周期双交叉设计,用液相色谱-质谱联用法测定20名健康男性志愿者血浆中格列齐特的浓度.结果:单次口服国产和进口格列齐特缓释片后的药动学参数分别为:tmax为(7.2±s 1.5)h和(6.9±1.4)h,cmax为(2.4±0.8)mg·L-1和(2.3±0.6)mg·L-1,t1/2为(13.4±1.2)h和(13.7±1.3)h,AUC0~60为(48±14)mg·h·L-1和(48±14)mg·h·L-1,AUC0~∞为(51±15)mg·h·L-1和(50±14)mg·h·L-1,平均滞留时间(MRT)为(22.4±1.9)h和(22.78±1.9)h.多次(60mg,6 d)口服国产和进口格列齐特缓释片后的稳态药动学参数分别为:tmax为(6.1±1.4)h和(6.5±1.4)h,cmax为(4.6±0.9)mg·L-1和(4.7±1.1)mg·L-1,cmin为(0.23±0.08)mg·L-1和(0.26±0.08)mg·L-1,稳态血药浓度均值(cav)为(1.6±0.3)mg·L-1和(1.6±0.3)mg·L-1,AUCss为(94±19)mg·h·L-1和(95±20)mg·h·L-1,波动度(DF)为(282±33)%和(283±43)%.单次和多次口服国产与进口格列齐特缓释片相对生物利用度分别为(102±9)%和(99±10)%.上述单次和多次给药的药动学参数经方差分析无显著差异(P>0.05).结论:双单侧t检验表明2种制剂具有生物等效性.%AIM: To compare the pharmacokinetics and relative bioavailability of the domestic and imported sustained-release tablets of gliclazide in healthy volunteers. METHODS:The study was performed by an four-period crossover design with singledose and multiple-dose administration. The plasmadrug concentrations of twenty male healthy volunteers were determined by liquid chromatography with mass spectrum detector method (LC-MS). RESULTS:The pharmacokinetic parameters after a single oral dose of the domestic and imported gliclazide tablets were (7.2+s 1.5) h and (6.9 +1.4) h for tmax, (13.4 ±1.2) h and (13.7 +1.3) h for t1/2, (2.4 +0.8) mg ·L-1and (2.3 ±0.6) mg· L-1 forcmax, (48 ±14)mg · h · L-1 and (48 +14) mg· h · L-1 forAUC0-60,(51+15) mg· h

  1. Evaluation of the efficacy and safety of repaglinide and gliclazide in treatment of type 2 diabetes by meta-analysis%瑞格列奈与格列齐特治疗2型糖尿病有效性及安全性的Meta分析

    陈慧; 李江华; 庄文斌


    Objective To evaluate the efficacy and safety of repaglinide,a kind of oral hypoglycemic agent, in the treatment of type 2 diabetes. Methods Recent published papers that chose randomized comparative trials to distinguish clinical effects between repaglinide and gliclazide were collected for meta-analysis. Results Total seven papers met this requirement and were selected for meta-analysis. When fixed effects model was adopted for fasting plasma glucose ( FPG) analysis, results showed that Z = 0. 28, P = 0. 78 , WMD = 0. 04 ( - 0. 25,0. 34). When random effects model was adopted for 2h postprandial blood glucose (PBG) analysis, results showed that Z = 5. 54, P <0. 00001, WMD = -1.91 ( -2.58, -1.23). When fixed effects model was adopted for HbAIC analysis, results showed that Z = 1. 33, P = 0. 18, WMD = -0. 19( -0.47, -0.09). When fixed effects model was adopted for hypoglycemia analysis, results showed that Z = 3. 63, P = 0. 0003 , WMD = 0. 24 (0. 11 , 0. 52 ). Conclusion There is no significant difference between repaglinide and gliclazide in decreasing the levels of FPG and HbAlC. However, repaglinide could further decrease the level of 2 h PBG and prevent against hypoglycemia compared with gliclazide.%目的 评价口服降糖药瑞格列奈治疗2型糖尿病的疗效及安全性.方法 检索至今已公开发表的关于比较瑞格列奈和格列齐特治疗2型糖尿病临床效应差异的随机对照试验论文,提取临床效应指标进行Meta分析.结果 7项随机对照试验纳入分析,采用固定效应模型对空腹血糖进行Meta分析,结果显示Z =0.28,P=0.78,WMD=0.04(-0.25,0.34);采用随机效应模型对餐后2小时血糖进行Meta分析,结果显示Z=5.54,P<0.00001,WMD=-1.91(-2.58,-1.23);采用固定效应模型对糖化血红蛋白值进行Meta分析,结果显示Z=1.33,P=0.18,WMD=-0.19(-0.47,-0.09);采用固定效应模型对低血糖进行Meta分析,结果显示Z=3.63,P=0.0003,WMD =0.24(0.11,0.52).结论 瑞格列奈与格列齐特

  2. Efficacy comparison and preliminary safety analysis of gliclazide modified-release combined with morning or evening taking metformin in patients with newly diagnosed type 2 diabetes mellitus%早餐或晚餐后服用二甲双胍在初诊2型糖尿病患者中的疗效对比及安全性初步分析

    张晓亚; 孙良阁


    Objective To compare the effect of gliclazide modified-release combined with morn ing or evening taking metformin to glycosylated hemoglobin A1 c (HbA1 c)and homeostasis model assessment(HOMA-IR and HOMA-β)on patients with newly diagnosed type 2 diabetes mellitus and its safety.Methods This 12-week study included 60 newly diagnosed type 2 diabetic patients who were randomly divided into two groups.Based on diet controlling and exercise therapy,patients in group A received gliclazide modified-release (diamicron) 60 mg (2 tablets) once daily before breakfast and metformin (glucophage) 850 mg(1 tablet) once daily after breakfast; patients in group B received gliclazide modifiedrelease tablet (diamicron) 60 mg (2 tablets) once daily before breakfast and metformin (glucophage) 850 mg (1 tablet) once daily after supper.Fasting blood glucose (FBG),Postprandial 2 h plasma glucose (2 h PG),Fasting insulin (F-ins),Postprandial 2 h insulin (P-ins),HbA1 c,Body weight,liver and kidney functions,triglyceride (TG),total cholesterol (TC),electrocardiogram (ECG),adverse drug reactions were measured and recorded.Results Glycosylated henoglobin A1c (HbA1c) in group A and B decreased (0.93 ± 0.63) % and (0.99 ± 0.89) %,respectively,there was no significant differences between the two groups (P > 0.05),HOMA-IR decreased 0.52 ± 0.62 in group A and 0.34 ± 0.59 in group B,there was no significant difference between the two groups (P > 0.05).HOMA-βincreased (13.59 ± 12.83) % in group A and (11.35 ± 15.40) % in group B,there was no significant difference between the two groups (P > 0.05).Conclusions Combination of gliclazide modified-release and metformin could decrease HbA1c,improve insulin resistence and increase β-cell function effectively,there is no significantly difference in morning or evening taking metformin.%目的 比较格列齐特缓释片联合不同时间(早或晚餐后)服用二甲双胍对初诊2型糖尿病患者糖化血红蛋白、胰岛素抵抗


    臧东莲; 张立艳



  4. Pharmacokinetics and bioequivalence study of Gliclazide tables in Chinese healthy volunteers%格列齐特片在健康人体内的药代动力学及生物等效性研究

    刘史佳; 张军; 居文政; 刘芳; 谈恒山


    目的研究格列齐特片在健康人体内的相对生物利用度和生物等效性.方法 20名健康成年男性志愿者采用随机分组自身交叉对照试验设计,单剂量口服80mg格列齐特片后,用高效液相色谱法测定血浆中药物浓度.结果格列齐特在0.104~12.48μg/ml浓度范围内线性良好(r=.999 88),平均回收率90.125%~104.6%,日内和日间精密度(RSD)均<10.0%.试验制剂和参比制剂的主要药代动力学参数:峰时(Tmax):(4.4±0.9)和(4.0±0.9)h;峰浓度(Cmax):(4.8±0.6)和(5.3±0.8)μg/ml;曲线下面积(AUC)0~48h:(86±29)和(88±33)mg·L-1·h-1;AUC0~∞:(99±45)和(103±58)mg·L-1·h-1;消除半衰期(T1/2):(13±4)和(14±5)h.以AUC0~48h计算的受试制剂的相对生物利用度为(99±9)%.结论建立的分析方法准确灵敏,统计学分析表明两种制剂生物等效.

  5. Hypoglycaemia when adding sulphonylurea to metformin

    Andersen, Stig Ejdrup; Christensen, Mikkel


    of hypoglycaemia was lowest with gliclazide compared to glipizide (OR 0.22, CrI: 0.05 to 0.96), glimepiride (OR 0.40, CrI: 0.13 to 1.27), and glibenclamide (OR 0.21, CrI: 0.03 to 1.48). A major limitation is varying definitions of hypoglycaemia across studies. CONCLUSIONS: When added to metformin, gliclazide...

  6. Pharmacokinetics and Bioequivalence of Gliclazide Sustained-release Tablets in Healthy Volunteers after High Fat Diet%格列齐特缓释片在健康人高脂饮食后的药动学及生物等效性

    杨丽君; 朱运贵


    研究了格列齐特缓释片在健康人高脂饮食后的药动学和生物等效性.以进口胶囊为参比制剂,国产胶囊为受试制剂,18名健康受试者高脂饮食后随机交叉口服受试制剂和参比制剂60 mg.以格列吡嗪为内标,采用HPLC-UV法测定血药浓度.结果显示:高脂饮食后受试制剂和参比制剂的主要药动学参数为:Cmax(2.457±0.376)和(2.443±0.310)mg/L,AUC0-t,(40.782±7.653)和(39.341±5.389)mg·h·L-1,AUC0-∞(42.456±7.029)和(42.913±8.154)mg·h·L-1,tmax(5.39±0.85)和(5.50±0.71)h.受试制剂的相对生物利用度为(103.3±8.4)%,两制剂具有生物等效性.

  7. Unchanged gene expression of glycogen synthase in muscle from patients with NIDDM following sulphonylurea-induced improvement of glycaemic control

    Vestergaard, H; Lund, S; Bjørbaek, C


    We have previously shown that the mRNA expression of muscle glycogen synthase is decreased in non-insulin-dependent diabetic (NIDDM) patients; the objective of the present protocol was to examine whether the gene expression of muscle glycogen synthase in NIDDM is affected by chronic sulphonylurea...... treatment. Ten obese patients with NIDDM were studied before and after 8 weeks of treatment with a weight-maintaining diet in combination with the sulphonylurea gliclazide. Gliclazide treatment was associated with significant reductions in HbA1C (p=0.001) and fasting plasma glucose (p=0.005) as well...... metabolism (p=0.02) was demonstrated in teh gliclazide-treated patients when compared to pre-treatment values. In biopsies obtained from vastus lateralis muscle during insulin infusion, the half-maximal activation of glycogen synthase was achieved at a significantly lower concentration of the allosteric...

  8. Hypoglycaemia

    Piya Sen Gupta; Andrea N Green; Tahseen A Chowdhury


    @@ A 58 year old white man who has had type 2 diabetes for 10 years is concerned about increasingly frequent hypoglycaemic episodes, usually in the late afternoon.He has been taking a stable, once daily dose of basal insulin glargine 14 units for two years, as well as twice daily gliclazide 160 mg and metformin 1000 mg.

  9. Rational choice of monotherapy for the treatment of type 2 diabetes mellitus based on the pharmacoeconomical analysis

    Tatyana Ivko


    Full Text Available Research was conducted to scientific justification of rational choice of monotherapy diabetes mellitus (DM type 2 based on the pharmacoeconomical analysis. It has been found that the unit of efficiency was the cheapest in the scheme of the monotherapy with gliclazide and most expensive – in the scheme of the monotherapy with metformin.

  10. Drug: D01599 [KEGG MEDICUS

    Full Text Available D01599 Drug Gliclazide (JP16/INN); Glimicron (TN) C15H21N3O3S 323.1304 323.4105 D01599.gif Antidiabetic...ents affecting metabolism 396 Antidiabetic agents 3961 Sulfonylureas D01599 Glicl

  11. 2003~2005年我院口服降糖药物利用分析%Drug utilization analysis of oral hypoglycemic agents in our hospital during the period of 2003 ~ 2005

    辛海莉; 蔡雯雯; 郭蔚


    To assess the drug utilization and tendency of progress of oral hypoglycemic agents in our hospital and to provide references for rational administration clinically. Methods: DDDs, sales quantities, sales expenses and the ratio of sales expenses sequencing to that of DDDs in our hospital during the period of 2003 ~ 2005 were analyzed statistically with the method of DDDs analysis. Results:The top two antidiabetic drugs according to DDDs were melbine ( dimethyl diguanide) and gliclazide three successive years. The DDDs of acarbose increased dramatically. Which blood glucose regulatsry drugs ranked lower, the ratio of sales expenses sequencing to that of DDDs of glipizide and gliclazide controlled release pellets was equal or about, whereas that of rosiglitazone, acarbose(glucobay) and glimepiride was less than 1. Conclusion:The study shows that the drug utilization of oral hypoglycemic agents in our hospital is basically rational and is in accordance with the trend of advancement and drug therapeutic strategies of diabetes mellitus.

  12. Effect of Correlation Structure in Generalized Estimating Equation and Quasi Least Square: An Application in Type 2 Diabetes Patient

    Dilip C Nath


    Full Text Available The Quasi-Least Squares (QLS is useful for different correlation structure with attachment of Generalized Estimating Equation (GEE. The purpose of this work is to compare the regression parameter in the presence of different correlation structure with respect to GEE and QLS method. The comparison of estimated regression parameter has been performed in clinical trial data set; studying the effect of drug treatment (metformin with pioglitazone Vs (gliclazide with pioglitazone in type 2 diabetes patients. In case of QLS, the correlation coefficient of post-parandinal blood sugar (PPBS under tridiagonal correlation is 0.008 while it failed to produce by GEE. It has been found that the combination of metformin with pioglitazone is more effective as compared to the combination of gliclazide with pioglitazone.

  13. Renoprotective effect of hypericum perforatum against diabetic nephropathy in rats: Insights in the underlying mechanisms.

    Abd El Motteleb, Dalia M; Abd El Aleem, Dalia I


    Oxidative stress and inflammation play a key role in the initiation and progression of diabetic nephropathy (DN). The present study aimed to investigate the possible protective effect of hypericum perforatum (HP) against DN. Rats were allocated into six groups; control: received normal saline, diabetic untreated (DM): received single dose of streptozotocin (STZ) after injection of nicotinamide (NA), gliclazide: received STZ,NA+ gliclazide (10mg/kg), DM+HP50, DM+HP100, DM+HP200:received STZ,NA and HP 50, 100, 200 mg/kg respectively. Gliclazide and HP were administered daily via gavage for 8 weeks. Serum glucose, insulin, kidney function and histopathological picture were assessed. Furthermore, oxidative/nitrosative stress, inflammatory cytokines, apoptotic and fibrotic markers were measured. Diabetic untreated group showed increase in serum glucose, urea, creatinine with albuminurea. Renal expression of protein for nuclear factor kappa-B (NF-кB), renal expression of inducible nitric oxide synthase (iNOS), cyclooxygenase II (COXII), collagen IV, fibronectin were elevated. Malondialdehyde (MDA), nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), intracellular adhesion molecule (ICAM-1), monocellular chemoattractant protein-1 (MCP-1), tumor growth factor- β (TGF-β), caspase-3 and cytochrome c contents were also increased consequently with decline of serum insulin, expression of peroxisome proliferator-activated receptor (PPARγ), renal reduced glutathione (GSH) content and superoxide dismutase (SOD) activity. Treatment with either gliclazide or HP mitigated the deleterious effects of STZ on the tested parameters. These findings indicate for the first time that HP may have a renoprotective effect against DN through reduction of oxidative/nitrosative stress, enhancement of antioxidant defense mechanisms, decline of inflammatory cytokines, antifibrotic, antiapoptotic and blood glucose lowering properties. This article is protected by

  14. A severe case of vasoplegic shock following metformin overdose successfully treated with methylene blue as a last line therapy

    Graham, Rachel Erin; Cartner, Michaela; Winearls, James


    A 44-year-old man presented to hospital 24 h after an intentional overdose of metformin and gliclazide. He had a critical metabolic acidosis on presentation with a pH of 6.88, and very rapidly deteriorated into distributive shock refractory to large volume fluid resuscitation and massive doses of vasopressors. We introduced a methylene blue infusion as a rescue therapy in an attempt to improve the patient's haemodynamics, which was successful. The patient made a full recovery with no long-term sequelae. PMID:26150642

  15. Effect of immunosuppressive and other drugs on the cortisol-cortisone shuttle in human kidney and liver.

    Quinkler, M; Jussli, J; Bähr, V; Pfeiffer, A F H; Lepenies, J; Diederich, S


    Impaired 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) has been suggested in patients with hypertension or renal disease, where it may contribute to sodium retention and hypertension. 11beta-HSD1, which is expressed predominantly in liver and adipose tissue, influences glucose homeostasis and fat distribution by altering intracellular cortisol (F) concentrations. We tested immunosuppressive drugs that cause hypertension, and substances that interfere with steroidogenesis or influence glucose homeostasis for their ability to influence the inhibition of 11beta-HSD isozymes. For inhibition experiments, we used microsomes prepared from unaffected parts of human liver segments and resected human kidney cortex because of hepatocarcinoma or renal cell cancer. The inhibitory potency of several compounds was evaluated in concentrations from 10(-9)-10(-5) mol/l. Only sirolimus, but not cyclosporine A, tacrolimus, mycophenolate mofetil, or azathioprine showed a slight inhibition of 11beta-HSD2 activity. None of the drugs that inhibit steroidogenesis (suramine, mitotane, etomidate, and aminogluthethimide) or steroid metabolism (rifampicine) influenced 11beta-HSDs, nor did ginsenoides Re, Rc, and Rb1. Among sulfonylureas, only gliclazide decreased significantly 11beta-HSD1 activity. Increased blood pressure due to immunosuppressive drugs is probably not caused by direct inhibition of 11beta-HSD2. An additional glucose lowering effect of sulfonylurea gliclazide may be due to its ability to inhibit 11beta-HSD1.

  16. In vitro and in vivo evaluation of a novel push-pull osmotic pump with orifices on both side surfaces.

    Li, Wei; Du, Gani; Yang, Xinggang; Zhang, Zhihong; Nie, Shufang; Peng, Bo; Pan, Weisan


    A novel push-pull osmotic pump (PPOP) was developed for delivery of water-insoluble drug gliclazide. Compared to conventional PPOP, which only had orifice(s) on the side of the drug layer, the novel PPOP had orifices of the same diameter on both side surfaces. The in vitro drug-release behavior of both novel PPOP and conventional PPOP were studied and compared; it was found that the drug-release rate of both kinds of PPOP could be influenced by coating level and core hardness whereas orifice size did not have much influence on it, and the study also showed that none of the former factors could influence the similarity of the drug-release profiles of the two kinds of PPOP. Mechanism of drug release from novel PPOP was illustrated using Poiseuille's law of lamina flow, and it was found that under regular formulation, the dissolution profiles of the two kinds of PPOP were similar. In vivo study also showed that the concentration-time profiles of gliclazide in plasma of the two PPOP were comparable and both of them had good in vitro-in vivo correlation. By simply drilled on both side surfaces, the novel PPOP did not need side identification when drilled, so it was more suitable for industrial manufacture than the conventional ones.

  17. Do geriatrics require dose titration for antidiabetic agents?

    R Shastry


    Full Text Available Objective: To evaluate the antidiabetic drug dosage differences between geriatric and nongeriatric diabetics with reference to duration of disease and creatinine clearance (Crcl. Materials and Methods: Prospective study conducted for 6 months in a tertiary care hospital. Patients with type 2 diabetes mellitus were grouped into geriatric (age ≥60 years and nongeriatric (age <60 years. Patients′ demographic data, duration of diabetes, medication, and serum creatinine were recorded. Crcl was calculated using Cockcroft-Gault formula. Doses of sulfonylureas (SU were converted into equivalent doses, taking glibenclamide as standard. Univariate analysis was done for comparison of drug doses between groups. Result: A total of 320 geriatric and 157 nongeriatric diabetics completed the study. The duration of diabetes and Crcl adjusted dose reduction of glibenclamide (mean dose: Geriatrics 7.2±0.4 mg, nongeriatrics 9.6±0.7 mg; P=0.01 and gliclazide (mean dose: Geriatrics 85.5±11.5 mg, nongeriatrics 115.3±32.7 mg; P=0.42 was 25%, glimepiride (mean dose: Geriatrics 1.62±0.13 mg, nongeriatrics 2.1±0.18 mg; P=0.06 was 22%. Glipizide did not require dose reduction. Mean converted equivalent dose of sulfonylurea monotherapy was significantly lower in geriatrics than nongeriatrics (3.2±0.5 vs 6.4±1.02 mg; P=0.01 and showed 50% dose reduction. Mean dose of metformin was lower in geriatrics (901±32.2 mg vs 946.7±45.8 mg; P=0.45 and showed 5% reduction in dosage. There was no difference in the mean drug doses of thiazolidinediones and insulin between the groups. Conclusion: A substantial dose reduction of glibenclamide (25%, gliclazide (25%, glimepiride (22%, and metformin (5% in geriatrics compared to nongeriatrics was observed. Smaller dosage formulations like 0.75 mg glibenclamide, 0.5 mg glimepiride, 20 mg gliclazide, and 250 mg metformin may be of value in geriatric diabetic practice.

  18. Application of oral hypoglycemic agent in Our Hospital in 2013%我院2013年门诊口服降糖药临床应用分析

    余彬; 王述蓉


    Objective:To make out the current situation and trend of oral hypoglycemic agent used in hospital and to make objective evaluation. Methods:The use of oral hypoglycemic agent in our hospital in 2013 was analyzed retrospectively in respect of consumption sum, DDDs .RESULTS:The top 3 oral hypoglycemic agent of consumption sum were Repaglinide, Acarbose and Glipizide.The top 3 oral hypoglycemic agent in respect of DDDs were Glipizide, Gliclazide Sustained-release Tablets and Glibenclamide. DDDc of Glibenclamide Glipizide and Gliclazide Sustained-release Tablets were the top 3.Conclusion:The use of oral hypoglycemic agent used in our hospital is rational on the whole, Acarbose of Glycosidase inhibitors and Gliclazide of Sulfonylureas are the most common because their good effects and few adverse reactions.%目的:对我院2013年门诊口服降糖药临床应用情况及趋势作出客观评价。方法:统计我院2013年门诊口服降糖药的销售金额、用药频度(DDDs)等,进行回顾性分析。结果:我院2013年口服降糖药销售金额排序前3位的是瑞格列奈片、阿卡波糖、格列吡嗪;DDDs排序前3位是格列吡嗪、格列齐特缓释片、格列苯脲片;日均费用前3位为格列苯脲片、格列吡嗪片、格列齐特缓释片。结论:我院口服降糖药使用较合理,糖苷酶抑制剂阿卡波糖、磺脲类药物的格列齐特因其疗效好、不良反应较少等居主导地位。

  19. [Risk and benefit of sulfonylureas--their role in view of new treatment options for type 2 diabetes].

    Rustenbeck, Ingo


    Currently, the therapy with oral antidiabetic drugs undergoes major changes. The use of sulfonylureas is in marked decline. The major argument in favor of newer oral antidiabetic drugs is the lower risk of hypoglycemia. At the present time however, it is unclear whether DDP4 inhibitors or SGLT2 inhibitors lead to better outcomes with respect to cardiovascular events and overall mortality. Most evidence on the therapeutic use of sulfonylureas has been gained with glibenclamide and to some degree sulfonylureas and glibenclamide have become synonymous. Since sulfonylureas vary considerably in their affinity for the K(ATP) channel subtypes and in their pharmacokinetic properties, the epidemiological evidence that outcomes tend to be less favorable with glibenclamide than with glimepiride or gliclazide has gained some attention. Beyond debate is the efficacy of metformin to diminish cardiovascular events in type 2 diabetes, probably due to effects beyond the lowering of blood glucose.

  20. Antihyperglycemic activity of the ethanolic seed extract of Vernonia anthelminticum willd

    Karthikeyan A


    Full Text Available The investigation was carried out to study the effects of Vernonia anthelminticum Willd seed extract on blood glucose level. The antihyperglycemic efficacy of the ethanolic extract of the seed was evaluated in normal, glucose and alloxan induced diabetic rats. The extract exhibited significant hypoglycemic activity in all three animal models when compared with the control group. The activity was also comparable to that of the effect produced by a standard antidiabetic agent gliclazide, 25 mg/kg (p.o.. The results also indicated dose dependent effect. The hypoglycemia and antihyperglycaemia produced by the extract may be due to increased uptake of glucose at tissue level or increase in pancreatic beta-cell function or due to inhibition of intestinal absorption of glucose. The study indicated that the ethanolic extract is a potential antidiabetic agent and lends scientific support for its else′s in folk medicine.

  1. [Hemorheologic, metabolic and blood coagulation changes in diabetics in treatment with sulfanyl ureas].

    Cortinovis, A; Crippa, A; Sciacca, V; Caravaggio, V; Crippa, M


    A study was carried out to see if chronic treatment with a sulphanylurea with hypoglycaemic action, with also haemoactive action in terms of anti-platelet aggregation, profibrinolytic and antifibrinogenetic action also acted haemorheologically. For this purpose a group of patients treated with Gliclazide was compared with a group under treatment with Glibenclamide. A significant variation was noted in terms of an increase in erythrocyte filtrability and a diminution in erythrocyte aggregation with diminution in blood viscosity at low shear-rates. The absence of parallel modifications in quantitative corpuscular viscous factors, the early onset of the process, the real diminution in the sense of a reduction below the range of normality suggests that the effect is pharmacological and not mediated by metabolic compensation.

  2. Comparisons of anti-diabetic prescriptions of private practitioners and hospital prescribers: A survey

    Ananya Mandal


    Full Text Available Monotherapy as well as effective and safe combination therapy for diabetes is practiced widely by both private and government hospital prescribers. This study attempted to compare the prescriptions of government and private practitioners to obtain a fair idea of the trends of diabetes management in either group. Prescriptions for diabetic patients from both private practitioners and government medical college prescribers were collected. These were analyzed for parameters such as number and type of drugs, cost, and generic prescription. Private prescribers were not significantly different from hospital prescribers in terms of number of drugs per prescription, cost of therapy, and treatment regimens. However, there was a dearth of generic prescriptions from private consultants (33% vs. 9%. Metformin and Glimepiride were the most prescribed drugs in both groups. However, private practitioners preferred Gliclazide, Glipizide, and Glibenclamide more than hospital prescribers.

  3. Hypoglycemic of Cajanus scarabaeoides in glucose overloaded and streptozotocin-induced diabetic rats

    Suman Pattanayak


    Full Text Available In light of traditional claim of Cajanus scarabaeoides (L in the treatment of diabetes, we studied the effects of different solvent extracts in normal, glucose over loaded normal and streptozotocin-induced diabetic rats. The methanolic extract (500 mg/kg orally was produce significantly reduce blood glucose level at normal, glucose over loaded normal rats, and streptozotocin-induced diabetic rats 15 days treatment whereas petroleum ether and chloroform extract (500 mg/kg orally did not exhibit any significant effect on three groups of rats. Histopathology studies on pancreas streptozotocin-induced diabetic rats inflammatory changes were detected in pancreatic islets results from selectively destroy of insulin producing β-cells. These changes are inhibited by C. scarabaeoides methanolic extract and gliclazide. The antidiabetic activity of methanolic extract may be due to the presence of flavonoids.

  4. Effects of drugs on platelet function.

    Morse, E E


    Numerous drugs and chemicals affect the function of human blood platelets. The mechanism of action of some medications is partly understood. Aspirin is the most frequently involved drug. It appears to interfere with the platelet release reaction by acetylation of a platelet membrane protein which may be involved in the synthesis of prostaglandins. Other anti-inflammatory drugs, including indomethacin, phenylbutazone, ibuprophen (Motrin) and clonixin, also interfere with the release reaction but have a shorter acting course than aspirin. Some drugs stimulate adenylcyclase (gliclazide) or block phosphodiesterase, (dipyridamole, caffeine) both of which actions lead to an increase in adenosine cyclic 3':5' monophosphate (cAMP) and decrease aggregation by adenosine diphosphate (ADP). These interactions should be known to clinical scientists since patients using these medicaments may manifest abnormal platelet function tests in the laboratory and mild hemorrhagic syndromes in the clinic.

  5. Simultaneous Quantification of Antidiabetic Agents in Human Plasma by a UPLC–QToF-MS Method

    Fachi, Mariana Millan; Cerqueira, Letícia Bonancio; Leonart, Letícia Paula; de Francisco, Thais Martins Guimarães


    An ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry method for the simultaneous quantification of chlorpropamide, glibenclamide, gliclazide, glimepiride, metformin, nateglinide, pioglitazone, rosiglitazone, and vildagliptin in human plasma was developed and validated, using isoniazid and sulfaquinoxaline as internal standards. Following plasma protein precipitation using acetonitrile with 1% formic acid, chromatographic separation was performed on a cyano column using gradient elution with water and acetonitrile, both containing 0.1% formic acid. Detection was performed in a quadrupole time-of-flight analyzer, using electrospray ionization operated in the positive mode. Data from validation studies demonstrated that the new method is highly sensitive, selective, precise (RSD 0.99), free of matrix and has no residual effects. The developed method was successfully applied to volunteers’ plasma samples. Hence, this method was demonstrated to be appropriate for clinical monitoring of antidiabetic agents. PMID:27930700

  6. Sulfonylurea therapy improves glucose disposal without changing skeletal muscle GLUT4 levels in noninsulin-dependent diabetes mellitus subjects

    Vestergaard, H; Weinreb, J E; Rosen, A S


    A major pathological feature of noninsulin-dependent diabetes (NIDDM) is defective insulin-stimulated glucose transport in skeletal muscle. When NIDDM subjects are assessed as a group, GLUT4 gene expression in skeletal muscle varies widely and is not different from that in controls. Thus......, longitudinal studies are needed to assess whether changes in GLUT4 expression in muscle of NIDDM subjects could be responsible for changes in glucose disposal. The question is timely because recent studies in transgenic mice show that increasing GLUT4 expression can increase insulin-stimulated glucose uptake...... in vivo and in vitro. Here we use a longitudinal design to investigate the effects of 8 weeks of therapy with the sulfonylurea gliclazide on glycemic control, glucose tolerance, insulin-stimulated glucose disposal, and GLUT4 expression in muscle of 10 obese NIDDM subjects. Subjects were on a weight...

  7. Intensive glucose control and risk of cancer in patients with type 2 diabetes

    Stefansdottir, G; Zoungas, S; Chalmers, J


    : Preterax and Diamicron-MR Controlled Evaluation (ADVANCE) trial ( NCT00145925) were studied. Cancer incidence and cancer mortality was compared in groups randomised to intensive or standard glucose control. Information on events during follow-up was obtained from serious adverse event...... reports and death certificates. HRs (95% CI) were calculated for all cancers, all solid cancers, cancer deaths and site-specific cancers. RESULTS: After a median follow-up of 5 years, 363 and 337 cancer events were reported in the intensive and standard control groups, respectively (incidence 1...... death) [corrected].Across all the major organ systems studied, no significant differences in the cancer incidences were observed in the intensive and standard control groups. CONCLUSIONS/INTERPRETATIONS: More intensive glucose control achieved with a regimen that included greater use of gliclazide...

  8. The incidence of mild and severe hypoglycaemia in patients with type 2 diabetes mellitus treated with sulfonylureas: a systematic review and meta-analysis.

    Schopman, J E; Simon, A C R; Hoefnagel, S J M; Hoekstra, J B L; Scholten, R J P M; Holleman, F


    Patients with type 2 diabetes mellitus using sulfonylurea derivatives or insulin may experience hypoglycaemia. However, recent data regarding the incidence of hypoglycaemia are scarce. We conducted a systematic review and meta-analysis to determine the proportion of patients with type 2 diabetes mellitus that experience hypoglycaemia when treated with sulfonylurea or insulin. We searched MEDLINE and EMBASE for randomized controlled trials that compared incretin-based drugs to sulfonylureas or insulin and assessed hypoglycaemia incidence in the latter therapies. Subgroup and meta-regression analyses were performed to study possible associations with potential risk factors for hypoglycaemia. Data of 25 studies were extracted, 22 for sulfonylurea and 3 for insulin. Hypoglycaemia with glucose ≤3.1 mmol/L or ≤2.8 mmol/L was experienced by 10.1% [95% confidence interval (CI) 7.3-13.8%] and 5.9% (95% CI 2.5-13.4%) of patients with any sulfonylurea treatment. Severe hypoglycaemia was experienced by 0.8% (95% CI 0.5-1.3%) of patients. Hypoglycaemia with glucose ≤3.1 mmol/L and severe hypoglycaemia occurred least frequently with gliclazide: in 1.4% (95% CI 0.8-2.4%) and 0.1% (95% CI 0-0.7%) of patients, respectively. None of the risk factors were significant in a stepwise multivariate meta-regression analysis. Too few studies had insulin as comparator, so these data could not be meta-analysed. The majority of patients with type 2 diabetes mellitus on sulfonylurea therapy in clinical trials remain free of any relevant hypoglycaemia. Gliclazide was associated with the lowest risk of hypoglycaemia. Because participants in randomized controlled trials differ from the general population, care should be taken when translating these data into clinical practice.

  9. Within-Sulfonylurea-Class Evaluation of Time to Intensification with Insulin (ZODIAC-43.

    Dennis Schrijnders

    Full Text Available Previous studies have shown that many within-class differences exist between sulfonylureas (SUs, however, whether differences exist regarding the time it takes between initiating an SU and the need to intensify treatment with insulin is unclear. The aim of this study was investigate the relationships between the three frequently used sulphonylureas, prescribed as dual therapy next to metformin, and the time needed to treatment intensification with either insulin or oral triple therapy in patients with type 2 diabetes mellitus.Zwolle Outpatient Diabetes project Integrating Available Care (ZODIAC is a prospective observational cohort study set in primary care in the Netherlands. Annually collected data on diabetes medication and clinical variables within ZODIAC are used to evaluate the primary outcome, time to insulin and secondary outcome, time to either insulin or triple oral therapy. For statistical analysis a time-dependent cox proportional hazard model was used.3507 patients were included in the analysis, with a mean age of 61 (SD 11.4 and a median HbA1c of 6.8% [IQR 6.4-7.4] (50.8 mmol/mol [IQR 46.4-57.4].The hazard ratio (HR for the primary endpoint was 1.10 (95% CI 0.78-1.54 for metformin/glimepiride and 0.93 (95% CI 0.67-1.30 for metformin/tolbutamide with metformin/gliclazide as reference group. The HR for the secondary outcome was 1.04 (95% CI 0.78-1.40 and 0.85 (95% CI 0.64-1.13, respectively.In this large Dutch primary care cohort, new users of neither gliclazide, glimepiride nor tolbutamide as dual therapy with metformin, resulted in differences in the time needed for further treatment intensification.

  10. Analysis of drug-protein binding using on-line immunoextraction and high-performance affinity microcolumns: Studies with normal and glycated human serum albumin.

    Matsuda, Ryan; Jobe, Donald; Beyersdorf, Jared; Hage, David S


    A method combining on-line immunoextraction microcolumns with high-performance affinity chromatography (HPAC) was developed and tested for use in examining drug-protein interactions with normal or modified proteins. Normal human serum albumin (HSA) and glycated HSA were used as model proteins for this work. High-performance immunoextraction microcolumns with sizes of 1.0-2.0 cm × 2.1mm i.d. and containing anti-HSA polyclonal antibodies were developed and tested for their ability to bind normal HSA or glycated HSA. These microcolumns were able to extract up to 82-93% for either type of protein at 0.05-0.10 mL/min and had a binding capacity of 0.34-0.42 nmol HSA for a 1.0 cm × 2.1mm i.d. microcolumn. The immunoextraction microcolumns and their adsorbed proteins were tested for use in various approaches for drug binding studies. Frontal analysis was used with the adsorbed HSA/glycated HSA to measure the overall affinities of these proteins for the drugs warfarin and gliclazide, giving comparable values to those obtained previously using similar protein preparations that had been covalently immobilized within HPAC columns. Zonal elution competition studies with gliclazide were next performed to examine the specific interactions of this drug at Sudlow sites I and II of the adsorbed proteins. These results were also comparable to those noted in prior work with covalently immobilized samples of normal HSA or glycated HSA. These experiments indicated that drug-protein binding studies can be carried out by using on-line immunoextraction microcolumns with HPAC. The same method could be used in the future with clinical samples and other drugs or proteins of interest in pharmaceutical studies or biomedical research.

  11. Anti-diabetic and renoprotective effects of aliskiren in streptozotocin-induced diabetic nephropathy in female rats.

    Mahfoz, Amal M; El-Latif, Hekma A Abd; Ahmed, Lamiaa A; Hassanein, Nahed M; Shoka, Afaf A


    Since chronic kidney disease due to diabetic nephropathy (DN) is becoming an ever larger health burden worldwide, more effective therapies are desperately needed. In the present study, the anti-diabetic and renoprotective effects of aliskiren have been evaluated in streptozotocin (STZ)-induced DN in rats. DN was induced by a single intraperitoneal injection of STZ (65 mg/kg). Three weeks after STZ, rats were divided into four groups; normal, diabetic, diabetic treated with gliclazide (10 mg/kg/day) for 1 month, and diabetic treated with aliskiren (50 mg/kg/day) for 1 month. At the end of the experiment, mean arterial blood pressure and heart rate were recorded. Rats were then euthanized and serum was separated for determination of glucose, insulin, kidney function tests, superoxide dismutase activity (SOD), adiponectin, and tumor necrosis factor-alpha (TNF-α). One kidney was used for estimation of malondialdehyde (MDA), reduced glutathione (GSH), and nitric oxide (NO) contents. Other kidney was used for histopathological study and immunohistochemical measurement of caspase-3 and transforming growth factor beta (TGF-β). In addition, islets of Langerhans were isolated from normal rats by collagenase digestion technique for in vitro study. Aliskiren normalized STZ-induced hyperglycemia, increased insulin level both in vivo and in vitro, normalized kidney function tests and blood pressure, and alleviated STZ-induced kidney histopathological changes. This could be related to the ability of aliskiren toward preserving hemodynamic changes and alleviating oxidative stress and inflammatory and apoptotic markers induced by STZ in rats. However, aliskiren was more effective than gliclazide in relieving STZ-induced DN. These findings support the beneficial effect of aliskiren treatment in DN which could be attributed to its anti-diabetic, renoprotective, antioxidant, anti-inflammatory, and anti-apoptotic effects. Moreover, clinical studies are required to establish the

  12. Comparative evaluation of the anti-diabetic activity of Pterocarpus marsupium Roxb. heartwood in alloxan induced diabetic rats using extracts obtained by optimized conventional and non conventional extraction methods.

    Devgan, Manish; Nanda, Arun; Ansari, Shahid Husain


    The aim of the present study was to assess the anti-diabetic activity of Pterocarpus marsupium Roxb. heartwood in alloxan induced diabetic rats using extracts obtained by optimized conventional and non conventional extraction methods. Aqueous and ethanol extracts of Pterocarpus marsupium heartwood were prepared by conventional methods (infusion, decoction, maceration and percolation) and non conventional methods, such as ultrasound-assisted extraction (UAE) and microwave-assisted extraction (MAE). The crude aqueous extracts were administered orally to both normal and alloxan induced male albino rats (Sprague-Dawley strain). The experimental set up consisted of 48 male albino rats divided into 6 groups: Normal control, diabetic control (sterile normal saline, 1 ml/100 g body weight), standard (gliclazide, 25 mg/1000g of body weight), groups 4-6 (crude aqueous percolation, optimized UAE and MAE extract, 250 mg/1000g of body weight). In acute treatment, the reduction of blood glucose level was statistically significant with the oral administration of UAE and percolation aqueous extracts to the hyperglycemic rats. In sub-acute treatment, the UAE aqueous extract led to consistent and statistically significant (p<0.001) reduction in the blood glucose levels. There was no abnormal change in body weight of the hyperglycemic animals after 10 days of administration of plant extracts and gliclazide. This study justifies the traditional claim and provides a rationale for the use of Pterocarpus marsupium to treat diabetes mellitus. The antidiabetic activity of Pterocarpus marsupium can be enhanced by extracting the heartwood by non conventional method of UAE.

  13. Influence of sulfonylureas on autophagy, apoptosis, and differentiation of the mice MC3T3-E1 cells%磺脲类药物对成骨细胞MC3T3-E1自噬、凋亡和分化功能的影响

    张丽; 季虹; 苏华; 刘兴艳; 辛衍代; 荣海钦


    目的 探讨磺脲类药物对成骨细胞自噬、凋亡及分化功能的影响. 方法 用磺酰罗丹明B染色检测不同浓度的格列本脲(GLB)、格列齐特(GLC)和格列吡嗪(GLP)对成骨细胞存活率的影响;Western blot分析3种磺脲类药物对细胞中自噬、凋亡标志蛋白表达的变化;Hoechst染色镜下观察上述药物对细胞凋亡的影响;通过对骨钙素(OCN)和碱性磷酸酶(ALP)的测定研究药物对细胞分化功能的影响. 结果 中、高浓度的GLB、GLC和GLP使MC3T3-E1细胞存活率降低.在药物干预下,MC3T3-E1细胞自噬和凋亡标志蛋白表达增加,mTOR信号途径无明显变化.3种药物可使细胞分泌OCN和ALP的能力下降. 结论 GLB、GLC和GLP可诱导成骨细胞MC3T3-E1发生自噬和凋亡,降低成骨细胞分化功能,且可能通过mTOR-非依赖途径诱导细胞自噬.%Objective To investigate the influence of sulfonylureas on the autophagy, apoptosis, and differentiation of the MC3T3-E1 cells. Methods Sulforhodamine B Assay was carried out to determine the effect of glibenclamide, gliclazide and glipizide in different concentrations on the cell survival. Western blot analysis was done to determine the protein levels of autophagy and apoptosis markers. Hoechst staining was applied to observe the impact of the three sulfonylureas on the cell apoptosis. The osteocalcin and alkaline phosphatase were assayed to assess the influence of these drugs on the differentiation of MC3T3-E1 cells. Results The intervention with glibenclamide, gliclazide, and glipizide in high concentrations made the survival rate of MC3T3-E1 cells decreased. Under the condition of drug intervention, the expression of autophagy and apoptosis markers of MC3T3-E1 cells was enhanced, whereas no remarkable changes were detected in mTOR signaling. The three sulfonylureas weakened the secretion of osteocalcin and alkaline phosphatase of MC3T3-E1 cells. Conclusion Glbenclamide, gliclazide, and glipizide

  14. Compound Danshen Dripping Pill Adjunctive Therapy for Type 2 Diabetes in 65 Cases%复方丹参滴丸辅助治疗2型糖尿病65例

    江霞; 徐文军; 高厚明; 郭彬


    目的 观察复方丹参滴丸辅助治疗2型糖尿病的临床效果.方法 选择2型糖尿病患者130例,随机均分为对照组和治疗组各65例,对照组口服格列齐特缓释片(80 mg,每日2次)、阿卡波糖片(100 mg,每日3次).治疗组在对照组基础上加服复方丹参滴丸(10丸,每日3次),疗程10周.结果 对照组总有效率为60.00%,治疗组总有效率为81.54%,两组总有效率比较有显著性差异(x2=5.46,P<0.05);两组治疗10周后空腹血糖、餐后2 h血糖、糖化血红蛋白、血清总胆固醇和甘油三酯均显著下降,且治疗组改善更明显.结论 复方丹参滴丸辅助治疗2型糖尿病疗效较好,值得临床推广.%Objective To study the clinical curative effect of Fufang Danshen Dripping Pill as an adjunctive therapy for type 2 diabetes. Methods A hundred and thirty patients with type 2 diabetes were randomly evenly assigned to control and treatment groups. The control group( n = 65) receive Gliclazide Sustained Release Tablets plus Acarbose Tablets for 10 weeks. and the treatment group( n =65) received Gliclazide Sustained Release Tablets+Acarbose Tablets in combination with Compound Danshen Dripping Pill for 10 weeks. Results The effective rate was 60. 00% in the control group and 81. 54% in the treatment group. There was significant difference in the total effective rate between the two groups (χ2 = 5. 46, P < 0. 05) . After 10 - week treatment. FBG, P2hBG, HbA1c, TC and TCJ were decreased significantly ( P < 0. 05), but the treatment group showing better improvement than control group. Conclusion Compound Danshen Dripping Pill as an adjunctive therapy for type 2 diabetes achieved satisfactory curative effect,whice deserves to be popularized in clinic.

  15. Analysis of cost-effectiveness of three different drugs in the treatment of type 2 diabetes mellitus%3种治疗方案在2型糖尿病患者中的成本-效果分析

    廖祖松; 陈雁


    Objective To explore the cost - effectiveness of three different drugs in the treatment of type 2 diabetes mellitus,to provide reference for choice drug. Methods From the patients using of metformin hydrochloride sustained release tablets、acarbose capsules、gliclazide sustained release tablets were randomly selected 80 cases, namely A group、 B group and C group,compared the cost - effectiveness and sensitivity analysis. Results A group of patients with C/E was 170.18, its value was minimal; C patients group of patients with ⊿ C/⊿ E was 6. 87, smaller than the other two groups. Conclusion The metformin hydrochloride sustained release tablets in the treatment of type 2 diabetes mellitus is the most economical solution, but the effect of gliclazide sustained -release tablets is the best, choice of drug should be based on the different clinical conditions.%目的利用成本-效果分析方法,评价3种方案治疗2型糖尿病的药物经济学效果,为治疗2型糖尿病药物选择提供参考.方法 从采用二甲双胍缓释片、阿卡波糖胶囊和格列齐特缓释片治疗的2型糖尿病患者中各随机选取80例,分别为A组、B组和C组,比较其药物经济学效果和敏感性分析.结果 A组C/E 170.18,最小;C组⊿C/⊿E 6.87,小于其他两组.结论 从药物经济学的角度分析,二甲双胍缓释片治疗2型糖尿病方案最经济,但是格列齐特缓释片疗效最佳,在临床治疗中应根据具体情况合理选药.

  16. Dipeptidyl peptidase-IV inhibitors are efficient adjunct therapy in HNF1A maturity-onset diabetes of the young patients--report of two cases.

    Katra, Barbara; Klupa, Tomasz; Skupien, Jan; Szopa, Magdalena; Nowak, Natalia; Borowiec, Maciej; Kozek, Elzbieta; Malecki, Maciej T


    In HNF1A maturity-onset diabetes of the young (MODY), sulfonylurea (SU) is the first-line treatment. Over time, such therapy fails, and additional treatment is required. Dipeptidyl peptidase IV (DPP-IV) inhibitors are new agents that lower blood glucose by prolonging the activity of circulating incretins. We applied DPP-IV inhibitors in two HNF1A MODY patients whose earlier therapeutic regimen included SU. Case 1, a 39-year-old woman, a carrier of the ArgR171X HNF1A mutation, with a 7-year history of diabetes was on 160 mg of gliclazide and 2,000 mg of metformin. Her initial hemoglobin A1c (HbA1c) level was 7.2%, while the mean glucose level on the CGMS((R)) (Medtronic, Northridge, CA) record was 162 mg/dL. Sitagliptine, in a dose of 100 mg/day, was added to the previous treatment. Case 2, a 62-year-old woman, a carrier of the IVS7nt-6G>A mutation, with a 41-year history of diabetes was treated with 240 mg/day gliclazide and 6 IU of insulin/day. Her initial HbA1c was 8.8%, and average glycemia reached 172 mg/dL. In her case, we started the combined therapy with 50 mg of vildagliptine twice daily. Patients were reexamined after 3 months, and HbA1c fell to 6.3% in both subjects. Similarly, significant improvement in glycemic control on CGMS was observed as the average glycemia decreased to 114 mg/dL and 134 mg/dL in Case 1 and Case 2, respectively. No episodes of hypoglycemia or other side effects were recorded. As intravenous glucose tolerance tests (IVGTTs) were performed before and after DPP-IV implementation, we were able to assess their impact on insulin secretion under fasting conditions. We saw a substantial rise in insulin level increment during IVGTT (by 9.8 and13.4 mIU/L in Case 1 and Case 2, respectively). DPP-IV inhibitors may be an effective tool of combined therapy in HNF1A MODY, and they seem to improve beta-cell function under fasting conditions.

  17. Remnant B-cell-stimulative and anti-oxidative effects of Persea americana fruit extract studied in rats introduced into streptozotocin - induced hyperglycaemic state.

    Rao, U S Mahadeva; Adinew, Bizuneh


    Insulin-stimulative and anti-oxidative effects of Persea americana fruit extract were evaluated using streptozotocin (STZ). Ethanol extract of P. americana in the concentration of 300 mg/kg body weight/rat /day was orally administered to rats introduced into STZ-induced hyperglycaemic state for a period of 30 days. After the treatment with avocado fruit extract, the elevated levels of blood glucose, glycosylated haemoglobin, blood urea and serum creatinine seen in the hyperglycaemic rats, reverted back to near normal. Similarly, significantly decreased plasma insulin and haemoglobin levels went back to near normal after the treatment, suggesting the insulin-stimulative effect of P. americana fruit. Determination of thiobarbituric acid reactive substances (TBARS), hydroperoxides and both enzymatic and non-enzymatic antioxidants, confirmed the anti-oxidative potential of avocado fruit extract which, in turn, might be responsible for its hypoglycaemic potential. Changes in activities of enzymes such as serum aspartate transaminase (AST), serum alanine transaminase (ALT), and serum alkaline phosphatase (ALP) seen in the control and experimental rats, revealed the tissue-protective nature of Persea americana fruits, while all of the analysed biochemical parameters were comparable to those obtained with gliclazide as a standard reference drug.

  18. Antidiabetic Effects of Add-On Gynostemma pentaphyllum Extract Therapy with Sulfonylureas in Type 2 Diabetic Patients

    V. T. T. Huyen


    Full Text Available Aims. To investigate the antidiabetic effect of the traditional Vietnamese herb Gynostemma pentaphyllum (GP together with sulfonylurea (SU in 25 drug-naïve type 2 diabetic patients. Methods. After 4-week treatment with gliclazide (SU, 30 mg daily, all patients were randomly assigned into 2 groups to add on GP extract or placebo extract, 6 g daily, during eight weeks. Results. After 4-week SU treatment, fasting plasma glucose (FPG and HbA1C decreased significantly (P<0.001. FPG was further reduced after add-on therapy with 2.9 ± 1.7 and 0.9 ± 0.6 mmol/L in the GP and placebo groups, respectively (P<0.001. Therapy with GP extract also reduced 30- and 120-minute oral glucose tolerance test postload values. HbA1C levels decreased approximately 2% units in the GP group compared to 0.7% unit in the placebo group (P<0.001. Conclusion. GP extract in addition to SU offers an alternative to addition of other oral medication to treat type 2 diabetic patients.

  19. [Sulfonylureas in today's blood glucose lowering therapy. New data on advantages and potential barriers of an "old" antidiabetic group].

    Winkler, Gábor


    Sulfonylurea compounds have been basic elements of antidiabetic treatment in type 2 diabetes for a long time. However, with the introduction of incretin type insulin secretagogues it is often arises, whether is still there a place for sulfonylureas in the today's therapy. To answer this question the author overviews general pharmaceutical characteristics of the sulfonylurea compounds as well as individual particularities of the second generation derivatives used at present in Hungary. The author details also the most important differences between incretin type drugs - first of all dipeptidyl peptidase-4 inhibitors - and sulfonylureas. On the basis of available data it can be concluded in accordance with the latest international guidelines, that sulfonylureas have still role in the blood glucose lowering therapy of type 2 diabetes, though they became somewhat pushed back among insulin secretagogue type drugs. If a sulfonylurea compound is the drug of choice, it is important to select the appropriate molecule (in case of normal renal function gliclazide or glimepiride). It is also important to re-educate the patient, as well as to apply the minimal dose providing the desired glycaemic effect.

  20. 沿海和内地两家医院口服降糖药利用分析%Analysis on the Durg Utilization of Oral Hypoglycaemic Agents in an Inland Hospital and a Coastal Hospital

    莫斌斌; 符成海


    To get information about the status of use of oral hypoglycaemic agents in an inland and coastal hospitals,the ordes of total cost and DDDs were employed to compare the use of oral hypoglycaemic agents in an inland hospital and a coastal hospital.Our results showed that the much less biguanides were used in the coastal hospital as compared with the inland hospital.It is conclinical practice included dimethyl biguanide,glipizide,gliclazide and glibenclamide.%目的:了解口服降糖药在沿海和内地两家医院的用药情况。方法:应用总金额排序法及用药频度(DDDs)排序法对1998~1999年沿海和内地两家医院口服降糖药的利用情况进行比较分析。结果:沿海地区使用双胍类降糖药的患者远远少于内地。结论:沿海地区肥胖型糖尿病患者少于内地。二甲双胍、格列吡嗪、格列齐特、格列本脲等目前用药活跃,仍为主要降糖药。

  1. Using highly sensitive C-reactive protein measurement to diagnose MODY in a family with suspected type 2 diabetes.

    Besser, Rachel E J; Jones, Jackie; McDonald, Timothy J; Smith, Rebecca; Shepherd, Maggie H; Hattersley, Andrew T


    The authors report an adolescent who was found to have diabetes on routine blood testing. The initial diagnosis was type 2 diabetes because she was obese, did not have type 1 diabetes antibodies and both parents had diabetes. Highly sensitive C-reactive protein (hsCRP) was low in the proband and her father (≤0.1 mg/l) indicating that type 2 diabetes was unlikely, and that hepatocyte nuclear factor 1-α-maturity onset diabetes of the young (HNF1A-MODY) was the most likely diagnosis. Following a genetic diagnosis of HNF1A-MODY in the proband and her father, both patients were treated with gliclazide, with improvement in HbA1c. This case highlights the challenges of making a correct diagnosis of MODY in young onset diabetes. The authors report the first case where hsCRP, an easily available biomarker, has been used on an individual level to determine appropriate genetic testing of MODY in a family whose main differential diagnosis was familial type 2 diabetes.

  2. Multi-residue analysis method for analysis of pharmaceuticals using liquid chromatography-time of flight/mass spectrometry (LC-TOF/MS) in water sample

    Al-Qaim, Fouad Fadhil; Abdullah, Md Pauzi; Othman, Mohamed Rozali


    In this work, a developed method using solid - phase extraction (SPE) followed by liquid chromatography - time of flight mass spectrometry (LC-ESI-TOF/MS) was developed and validated for quantification and confirmation of eleven pharmaceuticals with different therapeutic classes in water samples, Malaysia. These compounds are caffeine (CAF), prazosin (PRZ), enalapril (ENL), carbamazepine (CBZ), nifedipine (NFD), levonorgestrel (LNG), simvastatin (SMV), hydrochlorothiazide (HYD), gliclazide (GLIC), diclofenac-Na (DIC-Na) and mefenamic acid (MEF). LC was performed on a Dionex Ultimate 3000/LC 09115047 (USA) system. Chromatography was performed on a Thermo Scientific C18 (250 mm × 2.1 mm, i.d.: 5μm) column. Several parameters were optimised such as; mobile phase, gradient elution, collision energy and solvent elution for extraction of compounds from water. The recoveries obtained ranged from 30-148 % in river water. Five pharmaceutical compounds were detected in the surface water samples: caffeine, prazosin, enalpril, diclofenac-Na and mefenamic acid. The developed method is precise and accepted recoveries were got. In addition, this method is suitable to identify and quantify trace concentrations of pharmaceuticals in surface water.

  3. Quantitative Evaluation of Compliance with Recommendation for Sulfonylurea Dose Co-Administered with DPP-4 Inhibitors in Japan

    Motonobu Sakaguchi


    Full Text Available After the launch of dipeptidyl peptidase-4 (DPP-4, a new oral hypoglycemic drug (OHD, in December 2009, severe hypoglycemia cases were reported in Japan. Although the definite cause was unknown, co-administration with sulfonylureas (SU was suspected as one of the potential risk factors. The Japan Association for Diabetes Education and Care (JADEC released a recommendation in April 2010 to lower the dose of three major SUs (glimepiride, glibenclamide, and gliclazide when adding a DPP-4 inhibitor. To evaluate the effectiveness of this risk minimization action along with labeling changes, dispensing records for 114,263 patients prescribed OHDs between December 2008 and December 2010 were identified in the Nihon-Chouzai pharmacy claims database. The adherence to the recommended dosing of SU co-prescribed with DPP-4 inhibitors increased from 46.3% before to 63.8% after the JADEC recommendation (p < 0.01 by time-series analysis, while no change was found in those for SU monotherapy and SU with other OHD co-prescriptions. The adherence was significantly worse for those receiving a glibenclamide prescription. The JADEC recommendation, along with labeling changes, appeared to have a favorable effect on the risk minimization action in Japan. In these instances, a pharmacy claims database can be a useful tool to evaluate risk minimization actions.

  4. Role of oral hypoglycemic agents in the management of type 2 diabetes mellitus during Ramadan

    Mir Iftikhar Bashir


    Full Text Available It is obligatory for all adult Muslims to observe fast during the holy month of Ramadan, but sick individuals including those with diabetes mellitus are exempted from the duty of fasting. Specific medical advice must be provided to individual patients concerning the potential risks they must accept if they decide to fast. Any alteration in medications deemed necessary to provide an effective and safe antidiabetic regimen should be instituted well before the start of Ramadan. Diet-controlled patients and those well controlled on insulin sensitizers have low risk of hypoglycemia and may safely fast with some modification in the timing of the doses. Newer generation sulfonylureas (gliclazide MR and glimepiride have reasonable safety profile during Ramadan fasting and are economical options for a large number of diabetics worldwide, especially in the developing countries; older, long acting sulfonylureas like glibenclamide and chlorpropamide should be avoided during fasting. Oral DPP-IV inhibitors are important substitutes to sulfonylureas for patients with diabetes mellitus during fasting owing to their glucose-dependent mechanism of action, efficacy, and tolerability. This group of drugs causes a moderate A1c reduction, are weight neutral, and have a very low risk of hypoglycemia. Short-acting insulin secretagogues are an option in the subset of fasting diabetic patients who have predominantly post-prandial hyperglycemia.

  5. Antidiabetic activity of methanolic bark extract ofAlbizia odoratissima Benth. in alloxan induced diabetic albino mice

    Dinesh Kumar; Sunil Kumar; Sonia Kohli; Renu Arya; Jyoti Gupta


    Objective:To evaluate the antidiabetic potential of methanolic extract ofAlbizia odoratissima Benth. bark in alloxan induced diabetic mice.Methods: Group-Ⅰ (normal control) mice received only basal diet without any treatment. In Group-Ⅱ (Diabetic control) mice, diabetes was induced by alloxan (150 mg/kgi.p.) and received only Tween80, 5% v/v in normal saline. Group-Ⅲ and Group-Ⅳ mice received metformin (10 mg/kg) and gliclazide (10 mg/kg) as standard drugs. Group-Ⅴ and Ⅵ mice received methanolic bark extract ofAlbizia odoratissima at doses of250 and500 mg/kg body weightp.o., respectively.Results: The results of the study indicates thatAlbizia odoratissima bark extract significantly (P<0.01) reduced the blood sugar level. The bark extract also significantly reduced the levels of serum cholesterol, triglycerides, serum glutamic-oxaloacetic transaminase, serum glutamic-pyruvic transaminase, alkaline phosphatase and decreases level of total proteins in alloxan induced diabetic mice.Conclusions:Methanolic extract ofAlbizia odoratissima has protective effects on the protection of vital tissues (pancreas, kidney, liver, heart and spleen), thereby reducing the causation of diabetes in experimental animals.

  6. Strychnos nux-vomica seeds: Pharmacognostical standardization, extraction, and antidiabetic activity

    Rajesh Bhati


    Full Text Available Background: Strychnos nux-vomica, commonly known as kuchla, contains strychnine and brucine as main constituents. Minor alkaloids present in the seeds are protostrychnine, vomicine, n-oxystrychnine, pseudostrychnine, isostrychnine, chlorogenic acid, and a glycoside. Seeds are used traditionally to treat diabetes, asthma, aphrodisiac and to improve appetite. Objective: The present study was aimed to evaluate the various pharmacognostical characters and antidiabetic activity of S. nux-vomica seed. Materials and Methods: Pharmacognostical characters were performed as per the WHO guideline. Extraction was carried out in petroleum ether, chloroform, alcohol, hydroalcoholic, aqueous, and phytochemical constituents present in extracts were detected by different chemical tests. Among these extracts hydroalcoholic, aqueous extracts were evaluated for antidiabetic activity on the basis of extractive yield and phytoconstituents, in alloxan-induced diabetic rats using gliclazide as standard. Results: Various analytical values of S. nux-vomica extract were established. Phytoconstituents present in S. nux-vomica extracts were detected. Conclusion: S. nux-vomica extracts show antihyperglycemic activity in experimental animals.

  7. Place of sulfonylureas in the management of type 2 diabetes mellitus in South Asia: A consensus statement

    Sanjay Kalra


    Full Text Available Since their introduction in clinical practice in the 1950′s, Sulfonylureas (SUs have remained the main-stay of pharmacotherapy in the management of type 2 diabetes. Despite their well-established benefits, their place in therapy is inappropriately being overshadowed by newer therapies. Many of the clinical issues associated with the use of SUs are agent-specific, and do not pertain to the class as such. Modern SUs (glimepiride, gliclazide MR are backed by a large body of evidence, experience, and most importantly, outcome data, which supports their role in managing patients with diabetes. Person-centred care, i.e., careful choice of SU, appropriate dosage, timing of administration, and adequate patient counseling, will ensure that deserving patients are not deprived of the advantages of this well-established class of anti-diabetic agents. Considering their efficacy, safety, pleiotropic benefits, and low cost of therapy, SUs should be considered as recommended therapy for the treatment of diabetes in South Asia. This initiative by SAFES aims to encourage rational, safe and smart prescription of SUs, and includes appropriate medication counseling.

  8. Development of the model of pancreatic β-cell membrane chromatography and its chromatographiccharacteristics

    YANG Guangde; HE Langchong; BIAN Xiaoli; ZHAO Liang


    A new model of pancreatic β-cell membrane chromatography has been established by using a β-cell membrane stationary phase (β-CMSP) prepared by immobilizing the β-cell membrane onto the surface of silica carrier. The protein level and K+, Na+-ATP enzymatic activity of the β-CMSP were detected respectively. The surface characteristics of the β-CMSP were tested by using the scanning electron microscope and surface energy spectrometer. In this model, the column (10 mm × 2 mm, I.D.) packed with β-CMSP, 25 mmo1/L ammonium sulfate buffer solution (pH 7.4) as mobile phase with the flow rate of 0.2 mL/min at 37 ± 0.5℃ were used in the following studies. The retention characteristics of the sulfonylureas (gliquidone, glibenclamide, gliclazide and glipizide) were investigated under the chromatographic conditions above. The affinities of the sulfonylureas on β-cell membrane and receptor will be expressed by using the logk′ values (the logarithm of capacity factor of a solute) in the model. The correlation of the affinity with the pharmacological effect of the sulfonylureas was analyzed also.

  9. Mortality and cardiovascular risk associated with different insulin secretagogues compared with metformin in type 2 diabetes, with or without a previous myocardial infarction: a nationwide study

    Schramm, Tina Ken; Gislason, Gunnar Hilmar; Vaag, Allan


    % confidence intervals): 1.32 (1.24-1.40), glibenclamide: 1.19 (1.11-1.28), glipizide: 1.27 (1.17-1.38), and tolbutamide: 1.28 (1.17-1.39) were associated with increased all-cause mortality in patients without previous MI. The corresponding results for patients with previous MI were as follows: glimepiride: 1.......30 (1.11-1.44), glibenclamide: 1.47 (1.22-1.76), glipizide: 1.53 (1.23-1.89), and tolbutamide: 1.47 (1.17-1.84). Results for gliclazide [1.05 (0.94-1.16) and 0.90 (0.68-1.20)] and repaglinide and [0.97 (0.81-1.15) and 1.29 (0.86-1.94)] were not statistically different from metformin in both patients...... without and with previous MI, respectively. Results were similar for cardiovascular mortality and for the composite endpoint. Conclusion Monotherapy with the most used ISs, including glimepiride, glibenclamide, glipizide, and tolbutamide, seems to be associated with increased mortality and cardiovascular...

  10. Maltodextrin based proniosomes of nateglinide: bioavailability assessment.

    Sahoo, Ranjan Ku; Biswas, Nikhil; Guha, Arijit; Kuotsu, Ketousetuo


    The present study delineates the fabrication of maltodextrin based proniosomes of nateglinide and their potential as controlled delivery system for diabetic therapy. New Zealand albino male rabbits have been used as animal model for in vivo study. To evaluate the bioavailability of nateglinide proniosome, a rapid, simple and sensitive HPLC method with photodiode array detection was developed and validated to determine nateglinide in rabbit plasma. Chromatographic separation was achieved by a reverse phase C18 column using a mixture of acetonitrile:methanol:10mM phosphate buffer (pH 3.5) in the ratio of 56:14:30 (%v/v) as the mobile phase at a flow rate of 1.0ml/min and quantified based on drug/IS peak area ratios. Gliclazide was used as the internal standard. The intra- and inter-day relative standard deviations of four tested concentrations were below 2%. The nateglinide proniosome formulation exhibited significantly higher plasma concentration than those of pure drug. The study revealed that the rate and extent of absorption of nateglinide from the proniosomal formulation was comparatively enhanced that of pure drug. Maltodextrin based proniosomes of nateglinide is not only simple and cost efficient delivery but also offers a useful and promising carrier for diabetic therapy through oral administration.

  11. Targeting AGEs Signaling Ameliorates Central Nervous System Diabetic Complications in Rats

    Mohamed Naguib Zakaria


    Full Text Available Diabetes is a chronic endocrine disorder associated with several complications as hypertension, advanced brain aging, and cognitive decline. Accumulation of advanced glycation end products (AGEs is an important mechanism that mediates diabetic complications. Upon binding to their receptor (RAGE, AGEs mediate oxidative stress and/or cause cross-linking with proteins in blood vessels and brain tissues. The current investigation was designed to investigate the effect of agents that decrease AGEs signaling, perindopril which increases soluble RAGE (sRAGE and alagebrium which cleaves AGEs cross-links, compared to the standard antidiabetic drug, gliclazide, on the vascular and central nervous system (CNS complications in STZ-induced (50 mg/kg, IP diabetes in rats. Perindopril ameliorated the elevation in blood pressure seen in diabetic animals. In addition, both perindopril and alagebrium significantly inhibited memory decline (performance in the Y-maze, neuronal degeneration (Fluoro-Jade staining, AGEs accumulation in serum and brain, and brain oxidative stress (level of reduced glutathione and activities of catalase and malondialdehyde. These results suggest that blockade of AGEs signaling after diabetes induction in rats is effective in reducing diabetic CNS complications.


    Lucie Widowati


    Full Text Available Trigonella foenum-graecum L. (klabet is one of the Indonesian medicinal plants and can be used to decrease glucose blood level on sufferer of diabetic. The effect of hypoglycemic of klabet seed extract on albino male rats has been investigated. Hyper­glycemic was induced by alloxan tetrahydrate 125 mg/kg body weight. The doses of the klabet extract were administered orally during 3 days and 7 days. Plasma glucose level was measured by Tinder method. Decrease percentage of plasma glucose level in gliclazide 1.4 mg/200g body weight, klabet seed extract 140 (DI, 280 (DII and 560 (DIII mg/200g body weight after 3 days of administration were 26.2, 17.97, 17.21, 14.17 respectively and decrease percentage after 7 days of administration were 42.74, 41.22, 42.86, 34.77 res­pectively. The effect of hypoglycemic was observed on 140 mg/200g body weight and 280 mg/200g body weight (p>0.05.

  13. Antidiabetic Effects of Add-On Gynostemma pentaphyllum Extract Therapy with Sulfonylureas in Type 2 Diabetic Patients

    Huyen, V. T. T.; Phan, D. V.; Thang, P.; Ky, P. T.; Hoa, N. K.; Ostenson, C. G.


    Aims. To investigate the antidiabetic effect of the traditional Vietnamese herb Gynostemma pentaphyllum (GP) together with sulfonylurea (SU) in 25 drug-naïve type 2 diabetic patients. Methods. After 4-week treatment with gliclazide (SU), 30 mg daily, all patients were randomly assigned into 2 groups to add on GP extract or placebo extract, 6 g daily, during eight weeks. Results. After 4-week SU treatment, fasting plasma glucose (FPG) and HbA1C decreased significantly (P < 0.001). FPG was further reduced after add-on therapy with 2.9 ± 1.7 and 0.9 ± 0.6 mmol/L in the GP and placebo groups, respectively (P < 0.001). Therapy with GP extract also reduced 30- and 120-minute oral glucose tolerance test postload values. HbA1C levels decreased approximately 2% units in the GP group compared to 0.7% unit in the placebo group (P < 0.001). Conclusion. GP extract in addition to SU offers an alternative to addition of other oral medication to treat type 2 diabetic patients. PMID:23125867

  14. Palladium-catalysed transannular C-H functionalization of alicyclic amines

    Topczewski, Joseph J.; Cabrera, Pablo J.; Saper, Noam I.; Sanford, Melanie S.


    Discovering pharmaceutical candidates is a resource-intensive enterprise that frequently requires the parallel synthesis of hundreds or even thousands of molecules. C-H bonds are present in almost all pharmaceutical agents. Consequently, the development of selective, rapid and efficient methods for converting these bonds into new chemical entities has the potential to streamline pharmaceutical development. Saturated nitrogen-containing heterocycles (alicyclic amines) feature prominently in pharmaceuticals, such as treatments for depression (paroxetine, amitifadine), diabetes (gliclazide), leukaemia (alvocidib), schizophrenia (risperidone, belaperidone), malaria (mefloquine) and nicotine addiction (cytisine, varenicline). However, existing methods for the C-H functionalization of saturated nitrogen heterocycles, particularly at sites remote to nitrogen, remain extremely limited. Here we report a transannular approach to selectively manipulate the C-H bonds of alicyclic amines at sites remote to nitrogen. Our reaction uses the boat conformation of the substrates to achieve palladium-catalysed amine-directed conversion of C-H bonds to C-C bonds on various alicyclic amine scaffolds. We demonstrate this approach by synthesizing new derivatives of several bioactive molecules, including varenicline.

  15. Insulin and metformin may prevent renal injury in young type 2 diabetic Goto-Kakizaki rats.

    Louro, Teresa M; Matafome, Paulo N; Nunes, Elsa C; da Cunha, Fernanda Xavier; Seiça, Raquel M


    Type 2 diabetes is increasing at epidemic proportions throughout the world, and diabetic nephropathy is the principal cause of end stage renal failure. Approximately 40% of patients with type 2 diabetes may progress to nephropathy and a good metabolic control can prevent the development of diabetic renal injury. The aim of our study was to evaluate, in young type 2 diabetic Goto-Kakizaki (GK) rats fed with atherogenic diet, the effects of the anti-diabetic compounds insulin, metformin and gliclazide on renal damage. GK rats fed with atherogenic diet showed increased body weight and fasting blood glucose, total cholesterol, triglycerides, C-reactive protein and protein carbonyl levels and lower HDL-cholesterol concentration; renal markers of inflammation and fibrosis were also elevated. All the anti-diabetic agents ameliorated fasting glycaemia and insulin resistance but only insulin and metformin were able to improve glycoxidation, fibrosis and inflammation kidney parameters. Our data suggest that insulin and metformin treatments, improving glicoxidative, inflammatory and fibrotic renal damage markers, play a key role in the prevention of diabetic nephropathy.

  16. Overcome side identification in PPOP by making orifices on both layers.

    Zhang, Zhi-hong; Li, Wei; Nie, Shu-fang; Tang, Xin; Peng, Bo; Tian, Lei; Pan, Wei-san


    The original purpose of this research was to build a database for an expert system. Unexpectedly, it was found that the color-identifying device in push-pull osmotic pump (PPOP) manufacturing process could be unnecessary. Water-insoluble drug indapamide, gliclazide and dipyridamole were employed as model drugs. Bunches of conventional formulations were designed; and traditional preparation procedures were used. In vitro drug release was studied; and the similarity between the conditions of orifice only on the side of the drug layer and orifices of the same diameter on both sides was evaluated. It was found that the drug release from PPOP could be influenced by formulation and core hardness while it could hardly be influenced by orifice size. No significant difference was observed between the dissolution profiles of orifice only on the side of the drug layer and orifices of the same diameter on both sides. Mechanism of drug release was discussed. The conclusion was that the disadvantage of side identification in PPOP manufacturing process could be overcome by drilling orifices on both sides.

  17. Glycemic Effectiveness of Metformin-Based Dual-Combination Therapies with Sulphonylurea, Pioglitazone, or DPP4-Inhibitor in Drug-Naïve Korean Type 2 Diabetic Patients

    Lee, Young Ki; Song, Sun Ok; Kim, Kwang Joon; Cho, Yongin; Choi, Younjeong; Yun, Yujung; Kang, Eun-Seok; Cha, Bong Soo; Lee, Hyun Chul


    Background This study compared the glycemic effectiveness of three metformin-based dual therapies according to baseline hemoglobin A1c (HbA1c) to evaluate the appropriateness of the guideline enforced by the National Health Insurance Corporation of Korea for initial medication of type 2 diabetes (T2D). Methods This prospective observational study was conducted across 24 weeks for drug-naïve Korean T2D patients with HbA1c greater than 7.5%. Subjects were first divided into three groups based on the agent combined with metformin (group 1, gliclazide-modified release or glimepiride; group 2, pioglitazone; group 3, sitagliptin). Subjects were also classified into three categories according to baseline HbA1c (category I, 7.5%≤HbA1cpioglitazone, or sitagliptin showed similar glycemic effectiveness among drug-naïve Korean T2D patients. In addition, these regimens were similarly effective across a wide range of baseline HbA1c levels. PMID:24404518

  18. Diabetes mellitus and kidney disease in the elderly.

    Iglesias, Pedro; Heras, Manuel; Díez, Juan J


    Management of diabetic elderly patients with chronic kidney disease involves specific characteristics that affect both metabolic control and therapeutic measures. Blood glucose control targets should be individualised based on life expectancy, renal function, hypoglycaemia risk and comorbidity. Metformin may be used alone or in combination with other oral anti-diabetic drugs but must be discontinued when the glomerular filtration rate is less than 30 mL/min. Gliclazide and glipizide are sulfonylureas that do not require dose adjustment in chronic kidney disease but they should be avoided in cases of advanced kidney disease because of the risk of hypoglycaemia. Repaglinide is the only meglitinide recommended in these patients. Alpha-glucosidase inhibitors must be avoided in patients with a glomerular filtration rate of less than 25 mL/min or those undergoing dialysis. Pioglitazone does not require dose adjustment but it has potentially adverse effects in this population. Dipeptidyl peptidase-4 inhibitors are effective and well tolerated. Of the latter, linagliptin does not require dose adjustment. Glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter 2 inhibitors are not recommended in elderly patients with advanced kidney disease. Lastly, insulin therapy, particularly using the new insulin analogues, allows adequate management of hyperglycaemia in these patients, with different therapeutic regimens that must be individualised in order to avoid hypoglycaemia.

  19. Modulation of trichloroethylene in vitro metabolism by different drugs in human.

    Cheikh Rouhou, Mouna; Haddad, Sami


    Toxicological interactions with drugs have the potential to modulate the toxicity of trichloroethylene (TCE). Our objective is to identify metabolic interactions between TCE and 14 widely used drugs in human suspended hepatocytes and characterize the strongest using microsomal assays. Changes in concentrations of TCE and its metabolites were measured by headspace GC-MS. Results with hepatocytes show that amoxicillin, cimetidine, ibuprofen, mefenamic acid and ranitidine caused no significant interactions. Naproxen and salicylic acid showed to increase both TCE metabolites levels, whereas acetaminophen, carbamazepine and erythromycin rather decreased them. Finally, diclofenac, gliclazide, sulphasalazine and valproic acid had an impact on the levels of only one metabolite. Among the 14 tested drugs, 5 presented the most potent interactions and were selected for confirmation with microsomes, namely naproxen, salicylic acid, acetaminophen, carbamazepine and valproic acid. Characterization in human microsomes confirmed interaction with naproxen by competitively inhibiting trichloroethanol (TCOH) glucuronidation (Ki=2.329 mM). Inhibition of TCOH formation was also confirmed for carbamazepine (partial non-competitive with Ki=70 μM). Interactions with human microsomes were not observed with salicylic acid and acetaminophen, similar to prior results in rat material. For valproic acid, interactions with microsomes were observed in rat but not in human. Inhibition patterns were shown to be similar in human and rat hepatocytes, but some differences in mechanisms were noted in microsomal material between species. Next research efforts will focus on determining the adequacy between in vitro observations and the in vivo situation.

  20. Clinical management of carbamazepine intoxication during anti-tubercular treatment: a case report

    Massimo Calderazzo


    Full Text Available We describe a 67-year-old man with medical history of focal post-stroke seizure and type 2 diabetes mellitus treated with carbamazepine, clobazam, gliclazide, insulin glargine, and omeprazole we visited for the onset in the last 7 days of asthenia, cough with mucus, breathing difficulty, chest pain, and weight loss. After clinical and laboratory tests, pulmonary tuberculosis was diagnosed, and a treatment with isoniazid, ethambutol, pyrazinamide rifampicin, and pyridoxine was started. Therapeutic drug monitoring of tuberculosis treatment documented that all drugs were in normal therapeutic range. Four days after the beginning of the treatment, we documented the improvement of fever, and three days later the patient showed sleepiness, visual disorder and asthenia. Clinical and pharmacological evaluation suggested a carbamazepine toxicity probably related to a drug interaction (Drug Interaction Probability Scale score = 6. The impossibility to switch carbamazepine for another antiepileptic drug, due to a resistant form of seizure, induced the discontinuation of tuberculosis treatment, resulting in the normalization of serum carbamazepine levels in one day (10 µg/ml and in the worsening of fever, requiring a new clinical and pharmacological evaluation. The titration dosage of carbamazepine and its therapeutic drug monitoring allowed to continue the treatment with both antitubercular drugs and carbamazepine, without the development of adverse drug reactions. To date, tuberculosis treatment was stopped and clinical evaluation, radiology and microbiology assays documented the absence of tubercular infection and no seizures appeared (carbamazepine dosage 800 mg/bid; serum levels 9.5 µg/ml.

  1. Surfactant-Free Solid Dispersions of Hydrophobic Drugs in an Amorphous Sugar Matrix Dried from an Organic Solvent.

    Takeda, Koji; Gotoda, Yuto; Hirota, Daichi; Hidaka, Fumihiro; Sato, Tomo; Matsuura, Tsutashi; Imanaka, Hiroyuki; Ishida, Naoyuki; Imamura, Koreyoshi


    The technique for homogeneously dispersing hydrophobic drugs in a water-soluble solid matrix (solid dispersion) is a subject that has been extensively investigated in the pharmaceutical industry. Herein, a novel technique for dispersing a solid, without the need to use a surfactant, is reported. A freeze-dried amorphous sugar sample was dissolved in an organic solvent, which contained a soluble model hydrophobic component. The suspension of the sugar and the model hydrophobic component was vacuum foam dried to give a solid powder. Four types of sugars and methanol were used as representative sugars and the organic medium. Four model drugs (indomethacin, ibuprofen, gliclazide, and nifedipine) were employed. Differential scanning calorimetry analyses indicated that the sugar and model drug (100:1) did not undergo segregation during the drying process. The dissolution of the hydrophobic drugs in water from the solid dispersion was then evaluated, and the results indicated that the Cmax and AUC0-60 min of the hydrophobic drug in water were increased when the surfactant-free solid dispersion was used. Palatinose and/or α-maltose were superior to the other tested carbohydrates in increasing Cmax and AUC0-60 min for all tested model drugs, and the model drug with a lower water solubility tended to exhibit a greater extent of over-dissolution.

  2. Vildagliptin: a review of its use in type 2 diabetes mellitus.

    Keating, Gillian M


    Vildagliptin (Galvus®, Jalra®, Xiliarx®) is an orally administered dipeptidyl peptidase-4 (DPP-4) inhibitor. In patients with type 2 diabetes mellitus, vildagliptin 50 mg twice daily is indicated for use in combination with metformin or a thiazolidinedione, and vildagliptin 50 mg once daily is indicated for use in combination with a sulfonylurea. A fixed-dose combination of vildagliptin/metformin (Eucreas®, Icandra®, Zomarist®) is also available. This article reviews the clinical efficacy and tolerability of vildagliptin in patients with type 2 diabetes, as well as summarizing its pharmacological properties. The efficacy of monotherapy or combination therapy with oral vildagliptin in patients with type 2 diabetes has been examined in randomized, double-blind, multicentre trials. Monotherapy with vildagliptin 50 mg once or twice daily reduced glycosylated haemoglobin (HbA(1c)) from baseline to a significantly greater extent than placebo, according to the results of 12- to 52-week trials in patients with type 2 diabetes. In terms of the reduction from baseline in HbA(1c) seen in active comparator trials of 12-104 weeks' duration, the noninferiority of vildagliptin 50 mg twice daily was established versus acarbose or rosiglitazone, the noninferiority of vildagliptin 100 mg once daily (an off-label dosage) versus metformin was established in elderly patients and vildagliptin 50 mg twice daily was more effective than voglibose; however, the noninferiority of vildagliptin 50 mg twice daily versus metformin or gliclazide was not established in two other trials. Combination therapy with vildagliptin 50 mg twice daily plus metformin improved HbA(1c) to a significantly greater extent than monotherapy with metformin and/or vildagliptin alone in patients with type 2 diabetes whose disease was inadequately controlled by metformin monotherapy or who were treatment naive, according to the results of 12- or 24-week trials. In addition, vildagliptin 50

  3. The Evalution of Effects after Metformin Treatment in Patients with Schizophrenia and Type 2 Diabetes%精神分裂症合并2型糖尿病患者使用二甲双胍疗效评估



    目的:观察精神分裂症患者合并2型糖尿病使用二甲双胍的疗效。方法:在2003.01-2014.01在我院住院的精神分裂症合并2型糖尿病,且仅服用奥氮平控制精神症状,格列齐特降血糖的61例男性患者进行临床研究,随机分为两组,以30例继续单用格列齐特治疗为对照组,而治疗组的31例患者在使用格列齐特的基础上加用二甲双胍治疗,观察6个月后两组的空腹血糖及餐后2小时血糖,糖化血红蛋白(HbA1c)等指标的变化。结果:在连续使用口服降糖药物治疗6个月后,结果显示治疗组较对照组更有效降低空腹血糖及餐后2小时血糖,糖化血红蛋白(HbA1c)值。结论:精神分裂症合并2型糖尿病后合理使用二甲双胍后可达到良好的治疗效果。%Objective:To observe the effects after metformin treatment in patients with schizophrenia and type 2 diabetes.Methods:When we set up several conditions for those patients with schizophrenia and type 2 diabetes living in our hospital from 2003.01 to 2014.01,such as only taking Olanzapine and Glicla-zide,we eventually found 61 patients who could match it,and then we divided them into two groups at random,the 30 patients as control group would contin-ue to take Gliclazide,the other 3 1 patients as treatment group would take Gliclazide and metformin together,then after 6 months treatment,we collected those relevant data,such as FBG,PBG and HbA1c.Results:After 6 months treatment,the treatment group is better than the control group in decreasing those data of FBG,PBG and HbA1c.Conclusion:It would gain a good result when those patients take metformin reasonablly.

  4. Cooperation between cAMP signalling and sulfonylurea in insulin secretion.

    Shibasaki, T; Takahashi, T; Takahashi, H; Seino, S


    Although glucose is physiologically the most important regulator of insulin secretion, glucose-induced insulin secretion is modulated by hormonal and neural inputs to pancreatic β-cells. Most of the hormones and neurotransmitters evoke intracellular signals such as cAMP, Ca²⁺ , and phospholipid-derived molecules by activating G protein-coupled receptors (GPCRs). In particular, cAMP is a key second messenger that amplifies insulin secretion in a glucose concentration-dependent manner. The action of cAMP on insulin secretion is mediated by both protein kinase A (PKA)-dependent and Epac2A-dependent mechanisms. Many of the proteins expressed in β-cells are phosphorylated by PKA in vitro, but only a few proteins in which PKA phosphorylation directly affects insulin secretion have been identified. On the other hand, Epac2A activates the Ras-like small G protein Rap in a cAMP-dependent manner. Epac2A is also directly activated by various sulfonylureas, except for gliclazide. 8-pCPT-2'-O-Me-cAMP, an Epac-selective cAMP analogue, and glibenclamide, a sulfonylurea, synergistically activate Epac2A and Rap1, whereas adrenaline, which suppresses cAMP production in pancreatic β-cells, blocks activation of Epac2A and Rap1 by glibenclamide. Thus, cAMP signalling and sulfonylurea cooperatively activate Epac2A and Rap1. This interaction could account, at least in part, for the synergistic effects of incretin-related drugs and sulfonylureas in insulin secretion. Accordingly, clarification of the mechanism of Epac2A activation may provide therapeutic strategies to improve insulin secretion in diabetes.

  5. Control Study of Pharmacoeconomics about Elderly Diabetes Patients Drug Treatment Programmes%老年糖尿病患者药物治疗方案的药物经济学对照研究



    Objective:To investigate the pharmacoeconomics of drug economics drug treatment of senile diabetes patients.Method:150 cases of elderly diabetes patients,admitted from January 2012 to December 2013 ,by using the method of random number table were divided into observation group and control group ,75 cases in each group.Control group patients accepted treatment of Glimepiride combined with Metformin,observation group of patients accepted Gliclazide combined with Metformin,then to compare and statistic the curative effect of two groups of patients,low blood sugar occurrence ,treatment cost and the effect of pharmacoeconomics.Result:Two groups of patients in treatment effect,the incidence of hypoglycemia and cost comparison differences had no statistical significance(P>0.05).Observation group of patients with drug economics effect was significantly lower than the control group,the difference was statistically significant(P0.05);观察组患者药物经济学效果明显低于对照组,差异有统计学意义(P<0.05)。结论:格列美脲联合二甲双胍及格列齐特联合二甲双胍在老年糖尿病的临床效果均十分显著,从药物经济学角度考量,格列美脲联合二甲双胍更具优越性,值得推广。

  6. Simultaneous determination of asenapine and valproic acid in human plasma using LC-MS/MS:Application of the method to support pharmacokinetic study

    Ambavaram Vijaya Bhaskar Reddy; Nandigam Venugopal; Gajulapalle Madhavin


    Combination of asenapine with valproic acid received regulatory approval for acute treatment of schizophrenia and maniac episodes of bipolar disorders. A simple LC-MS/MS method was developed and validated for simultaneous quantification of asenapine and valproic acid in human plasma. Internal standards were added to 300μL of plasma sample prior to liquid-liquid extraction using methyl tertiary butyl ether (MTBE). Chromatographic separation was achieved on Phenomenex C18 column (50 mm ? 4.6 mm, 5μm) in isocratic mode at 40 1C. The mobile phase used was 10 mM ammonium formate-acetonitrile (5:95, v/v) at a constant flow rate of 0.8 mL/min monitored on triple quadrupole mass spectrometer, operating in the multiple reaction monitoring (MRM) mode. The injection volume used for LC-MS/MS analysis was 15μL and the run time was 2.5 min. These low run time and small injection volume suggest the high efficiency of the proposed method. The method was validated over the concentration range of 0.1-10.02 ng/mL and 10-20,000 ng/mL for asenapine and valproic acid respectively. The method recoveries of asenapine (81.33%), valproic acid (81.70%), gliclazide (78.45%) and benzoic acid (79.73) from spiked plasma samples were consistent and reproducible. The application of this method was demonstrated by a pharmacokinetic study in 8 healthy male volunteers with 5 mg asenapine and 250 mg valproic acid administration.

  7. 医药中间体高含氨、高含盐废水的处理技术%Treatment technology of pharmaceutical intermediate wastewater containing high ammonia and high salinity

    毕煜龙; 丁瑾佳; 何云芳


    某精细化工厂生产医药中间体格列齐特粗品、氨基杂环盐酸盐和酰亚胺,产生高含氨、高含盐废水.采用凝聚沉淀—三效蒸发浓缩预处理后,与地面冲洗水、设备清洗水等废水混合后通过微电解+A2/O工艺处理,处理后废水总排放口COD、BOD5、SS、氨氮、总氮均达到《化学合成类制药工业水污染物排放标准》(GB 21904—2008)中表2要求,AOX达到《污水综合排放标准》(GB 8978—1996)表4中二级标准.%A fine chemical plant produces pharmaceutical intermediate:gliclazide crude,amino heterocyclic hydro-chloride and imide,releasing wastewater containing high ammonia and high salinity.After pretreated by flocculation-three effect evaporation and concentration process,and mixed with ground rinsing water and equipment cleaning water,the wastewater is treated by micro electrolysis+A2/O process.After the treatment,the concentrations of COD,BOD5,SS,ammonia nitrogen,total nitrogen at the wastewater total discharge outlet can meet the requirements specified in table 2 of the Discharge Standard of Water Pollution in Chemical Synthesized Pharmaceutical Industry (GB 21904—2008),and the concentration of AOX meets the requirements specified in table 4 of the second grade of the Integrated Wastewater Discharge Standard(GB 8978—1996).

  8. Synthesis, Antimicrobial and Hypoglycemic Activities of Novel N-(1-Adamantylcarbothioamide Derivatives

    Ebtehal S. Al-Abdullah


    Full Text Available The reaction of 1-adamantyl isothiocyanate 4 with the various cyclic secondary amines yielded the corresponding N-(1-adamantylcarbothioamides 5a–e, 6, 7, 8a–c and 9. Similarly, the reaction of 4 with piperazine and trans-2,5-dimethylpiperazine in 2:1 molar ratio yielded the corresponding N,N'-bis(1-adamantylpiperazine-1,4-dicarbothioamides 10a and 10b, respectively. The reaction of N-(1-adamantyl-4-ethoxycarbonylpiperidine-1-carbothioamide 8c with excess hydrazine hydrate yielded the target carbohydrazide 11, in addition to 4-(1-adamantylthiosemicarbazide 12 as a minor product. The reaction of the carbohydrazide 11 with methyl or phenyl isothiocyanate followed by heating in aqueous sodium hydroxide yielded the 1,2,4-triazole analogues 14a and 14b. The reaction of the carbohydrazide 11 with various aromatic aldehydes yielded the corresponding N'-arylideneamino derivatives 15a–g. The compounds 5a–e, 6, 7, 8a–c, 9, 10a, 10b, 14a, 14b and 15a–g were tested for in vitro antimicrobial activity against certain strains of pathogenic Gram-positive and Gram-negative bacteria and the yeast-like fungus Candida albicans. The compounds 5c, 5d, 5e, 6, 7, 10a, 10b, 15a, 15f and 15g showed potent antibacterial activity against one or more of the tested microorganisms. The oral hypoglycemic activity of compounds 5c, 6, 8b, 9, 14a and 15b was determined in streptozotocin (STZ-induced diabetic rats. Compound 5c produced significant reduction of serum glucose levels, compared to gliclazide.

  9. Fisetin improves glucose homeostasis through the inhibition of gluconeogenic enzymes in hepatic tissues of streptozotocin induced diabetic rats.

    Prasath, Gopalan Sriram; Pillai, Subramanian Iyyam; Subramanian, Sorimuthu Pillai


    Liver plays a vital role in blood glucose homeostasis. Recent studies have provided considerable evidence that hepatic glucose production (HGP) plays an important role in the development of fasting hyperglycemia in diabetes. From this perspective, diminution of HGP has certainly been considered for the treatment of diabetes. In the present study, we have analyzed the modulatory effects of fisetin, a flavonoid of strawberries, on the expression of key enzymes of carbohydrate metabolism in STZ induced experimental diabetic rats. The physiological criterions such as food and fluid intake were regularly monitored. The levels of blood glucose, plasma insulin, hemoglobin and glycosylated hemoglobin were analyzed. The mRNA and protein expression levels of gluconeogenic genes such as phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) were determined by immunoblot as well as PCR analysis. Diabetic group of rats showed significant increase in food and water intake when compared with control group of rats. Upon oral administration of fisetin as well as gliclazide to diabetic group of rats, the levels were found to be decreased. Oral administration of fisetin (10 mg/kg body weight) to diabetic rats for 30 days established a significant decline in blood glucose and glycosylated hemoglobin levels and a significant increase in plasma insulin level. The mRNA and protein expression levels of gluconeogenic genes, such as phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase), were decreased in liver tissues upon treatment with fisetin. The results of the present study suggest that fisetin improves glucose homeostasis by direct inhibition of gluconeogenesis in liver. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Comparative DNA profiling, phytochemical investigation, and biological evaluation of two Ficus species growing in Egypt

    El-Sayeda A El-Kashoury


    Full Text Available Aim and Background: A comparison between two Ficus species, cultivated in Egypt, was carried out in this study. Their DNA analysis revealed that they are not closely related. Materials and Methods: The pharmacopoeial constants of the leaves showed higher total ash and acid insoluble ash in F. lyrata than in F. platypoda. The other parameters were close in both species. Preliminary phytochemical screening revealed the presence of carbohydrate and/or glycosides, tannins, flavonoids, sterols, and triterpenes in their leaves and was detected in traces in their stems. Results: Saponification of n-hexane extract of the leaves yielded 46% and 74.8% for the unsaponifiable matters and 20% and 15% for the fatty acids for F. platypoda and F. lyrata, respectively. n-Docosane (21.69% and n-heptacosane (33.77% were the major hydrocarbons in F. platypoda and F. lyrata, respectively. b-Sitosterol was the main sterol, palmitic (22.07% and carboceric (35.72% acids were the major identified saturated fatty acids in both species, while linoleic acid was the main unsaturated fatty acid (18.66% and 16.7% in both species, respectively. The acute toxicity study revealed that the two species were safe up to 2 g/kg. The antioxidant activity using 1,1-diphenyl-2-picrylhydrazyl (DPPH assay and pyrogallol as the standard was more significant for F. platypoda (232.6 μg/ml than for F. lyrata, (790.9 μg/ml. The oral antihyperglycemic activity in diabetic rats using alloxan revealed that the 80% ethanolic extract of the leaves of F. platypoda was more active than that of the leaves of F. lyrata in decreasing the blood glucose level at 200 mg/kg/day (107.9 ± 5.817, 127.2 ± 4.359 and 400 mg/kg/day (64.11 ± 4.358, 127.7 ± 6.889, respectively, when compared with the diabetic control gliclazide (172.3 ± 2.089. Conclusion: The results of this study provide evidence that the two Ficus species have antioxidant and antihyperglycemic activity, in the order F. platypoda and then F

  11. Anti-proliferative activity of oral anti-hyperglycemic agents on human vascular smooth muscle cells: thiazolidinediones (glitazones have enhanced activity under high glucose conditions

    de Dios Stephanie T


    Full Text Available Abstract Background Inhibition of vascular smooth muscle cell (vSMC proliferation by oral anti-hyperglycemic agents may have a role to play in the amelioration of vascular disease in diabetes. Thiazolidinediones (TZDs inhibit vSMC proliferation but it has been reported that they anomalously stimulate [3H]-thymidine incorporation. We investigated three TZDs, two biguanides and two sulfonylureas for their ability of inhibit vSMC proliferation. People with diabetes obviously have fluctuating blood glucose levels thus we determined the effect of media glucose concentration on the inhibitory activity of TZDs in a vSMC preparation that grew considerably more rapidly under high glucose conditions. We further explored the mechanisms by which TZDs increase [3H]-thymidine incorporation. Methods VSMC proliferation was investigated by [3H]-thymidine incorporation into DNA and cell counting. Activation and inhibition of thymidine kinase utilized short term [3H]-thymidine uptake. Cell cycle events were analyzed by FACS. Results VSMC cells grown for 3 days in DMEM with 5% fetal calf serum under low (5 mM glucose and high (25 mM glucose increased in number by 2.5 and 4.7 fold, respectively. Rosiglitazone and pioglitazone showed modest but statistically significantly greater inhibitory activity under high versus low glucose conditions (P 3H]-thymidine into DNA but did not increase cell numbers. Troglitazone inhibited serum mediated thymidine kinase induction in a concentration dependent manner. FACS analysis showed that troglitazone and rosiglitazone but not pioglitazone placed a slightly higher percentage of cells in the S phase of a growing culture. Of the biguanides, metformin had no effect on proliferation assessed as [3H]-thymidine incorporation or cell numbers whereas phenformin was inhibitory in both assays albeit at high concentrations. The sulfonylureas chlorpropamide and gliclazide had no inhibitory effect on vSMC proliferation assessed by either [3H

  12. 本社区卫生服务中心2011-2013年口服降糖药的应用分析%Analysis of the application of oral hypoglycemic agents in a community health service center during 2011-2013



    目的:了解本社区卫生服务中心口服降糖药的应用情况和趋势。方法:对本社区卫生服务中心2011-2013年口服降糖药的主要品种、销售金额、用药频度(DDDs)、限定日费用(DDC)等进行分类统计、综合分析。结果:口服降糖药销售总金额逐年上升,α-葡萄糖苷酶抑制剂3年来均占据销售金额排名第1位,格列齐特缓释片和二甲双胍片连续3年DDDs居第一、第二,DDC最大的3位依次是阿卡波糖片、伏格列波糖片、瑞格列奈片。结论:本中心口服降糖药应用合理,需求量逐年增加,主要以磺酰脲类为主。安全、有效、良好的依从性是糖尿病治疗药物发展的必然趋势。%Objective: To know the usage and trend of oral hypoglycemic agents in our hospital during 2011-2013. Methods: The main species, sales, DDDs and DDC of oral hypoglycemic agents were statistically classiifed and their utilization was comprehensively analyzed.Results: The sales for oral hypoglycemic agents had been increased year by year during 2011-2013 and α-glucosidase inhibitors were ranked number 1. Metformin was ranked ifrst and gliclazide zyban second in DDDs, and the largest three tablets in DDC were acarbose, voglibose and repaglinide.Conclusion: Use of oral hypoglycemic agents was basically reasonable in our hospital. Their demand has been increasing year by year. Sulfonylurea is a mainly used oral antidiabetic drug. The drugs with safety, effectiveness and good compliance are an inevitable development trend for diabetes therapy.

  13. Canagliflozin, dapagliflozin and empagliflozin monotherapy for treating type 2 diabetes: systematic review and economic evaluation.

    Johnston, Rhona; Uthman, Olalekan; Cummins, Ewen; Clar, Christine; Royle, Pamela; Colquitt, Jill; Tan, Bee Kang; Clegg, Andrew; Shantikumar, Saran; Court, Rachel; O'Hare, J Paul; McGrane, David; Holt, Tim; Waugh, Norman


    haemoglobin or body mass index. Data on elderly patients were lacking. CONCLUSIONS Dapagliflozin, canagliflozin and empagliflozin are effective in improving glycaemic control, with added benefits of some reductions in BP and weight. Adverse effects are urinary and genital tract infections in a small proportion of users. In monotherapy, the three drugs do not appear cost-effective compared with gliclazide or pioglitazone, but may be competitive against sitagliptin (Januvia, Boehringer Ingelheim, Bracknell, UK). FUNDING The National Institute for Health Research Health Technology Assessment programme. PMID:28105986

  14. 罗格列酮对高脂血症大鼠拮抗胰岛素抵抗及脂肪性肝损伤作用%Effects of rosiglitazone on antagonizing insulin resistance and adipose liver damnification in hyperlipemic rats

    郑琳颖; 潘竞锵; 林洁茹; 肖柳英; 李博萍; 韩超


    BACKGROUND: Some experiments indicated that applying rosiglitazone on diabetic animals lacking of insulin could not increase insulin and lower blood glucose obviously, which showed that rosiglitazone did not stimulate the excretion of rosiglitazone. The action of rosiglitazone in improving insulin resistance and the effects on the functions of liver and kidneys need more investigations.OBJECTIVE: To investigate whether rosiglitazone can improve the insulin resistance of rats with hyperlipemia, and analyze the possible mechanism.SETTINGS: Guangzhou Hospital of Traditional Chinese Medicine; Guangzhou Institute of Traditional Chinese Medicine and Materia MedicaDESIGN: A stratified randomized controlled animal trial.MATERIALS: Sixty-four Sprague-Dawley (SD) rats (Batch No. 2002A024), SPF grade, half male and half female,weighing 150 to 180 g, aged 6 to 8 weeks were purchased from Guangdong Medical Experimental Animal Center.Normal feed (total quantity of heat 6.9 kJ/g) was enriched with 23% protein, 53% carbohydrate and 5% fat. High fat emulsion (total quantity of heat 15.5 kJ/g) was enriched with 200 g/L lard, 200 g/L cholesterol, 10 g/L bile salt ox,200 g/L propylene glycol, 200 g/L tween-80. High fat and sugar feed (total quantity of heat 21.0 kJ/g) was enriched with 15% protein, 51% carbohydrate and 30% fat after adding 100 g/L glucose, 200 g/L lard and 100 g/L yolk powder then mixing and baking. Rosiglitazone was from GlaxoSmithKline Co Ltd. (Tianjin) (5 mg/tab, Batch No.02110012). Gliclazide was from Servier International and Tianjin Hua Jin Pharmaceutical Factory (100 mg/tab, Batch No.00232).METHODS: The experiment was carried out in Guangzhou University of Traditional Chinese Medicine from April to July in 2003. ① Sixty-four Sprague-Dawley rats, 16 of which were randomly sampled as the normal control group and had been fed with normal feed for 6 weeks. The others were modeled after medical literatures, each one was administered with high fat emulsion (10 m

  15. Clinical drugs that interact with St. John's wort and implication in drug development.

    Di, Yuan Ming; Li, Chun Guang; Xue, Charlie Changli; Zhou, Shu-Feng


    St. John's wort (Hypericum perforatum, SJW) is one of the most commonly used herbal antidepressants for the treatment of minor to moderate depression. A major safety concern about SJW is its ability to alter the pharmacokinetics and/or clinical response of a variety of clinically important drugs that have distinctive chemical structure, mechanism of action and metabolic pathways. This review highlights and updates the knowledge on clinical interactions of prescribed drugs with SJW and the implication in drug development. A number of clinically significant interactions of SJW have been identified with conventional drugs, including anticancer agents (imatinib and irinotecan), anti-HIV agents (e.g. indinavir, lamivudine and nevirapine), anti-inflammatory agents (e.g. ibuprofen and fexofenadine), antimicrobial agents (e.g. erythromycin and voriconazole), cardiovascular drugs (e.g. digoxin, ivabradine, warfarin, verapamil, nifedipine and talinolol), central nervous system agents (e.g. amitriptyline, buspirone, phenytoin, methadone, midazolam, alprazolam, and sertraline), hypoglycaemic agents (e.g. tolbutamide and gliclazide), immuno-modulating agents (e.g. cyclosporine and tacrolimus), oral contraceptives, proton pump inhibitor (e.g. omeprazole), respiratory system agent (e.g. theophylline), statins (e.g. atorvastatin and pravastatin). Both pharmacokinetic and pharmacodynamic components may play a role in the interactions of drugs with SJW. For pharmacokinetic changes of drugs by SJW, induction of cytochrome P450s (e.g. CYP2C9 and 3A4) and P-glycoprotein (P-gp) are considered the major mechanism. Thus, it is not a surprise that many drugs that interact with SJW are substrates of CYP3A4, CYP2C9 and P-gp. A comprehensive understanding of clinical drugs that interact with SJW has important implications in drug development. New drugs may be designed to minimize interactions with SJW; and new SJW formulations may be designed to avoid drug interactions. Further clinical and

  16. Effects of oral glucose-lowering drugs on long term outcomes in patients with diabetes mellitus following myocardial infarction not treated with emergent percutaneous coronary intervention - a retrospective nationwide cohort study

    Jørgensen Casper H


    Full Text Available Abstract Background The optimum oral pharmacological treatment of diabetes mellitus to reduce cardiovascular disease and mortality following myocardial infarction has not been established. We therefore set out to investigate the association between individual oral glucose-lowering drugs and cardiovascular outcomes following myocardial infarction in patients with diabetes mellitus not treated with emergent percutaneous coronary intervention. Materials and methods All patients aged 30 years or older receiving glucose-lowering drugs (GLDs and admitted with myocardial infarction (MI not treated with emergent percutaneous coronary intervention in Denmark during 1997-2006 were identified by individual-level linkage of nationwide registries of hospitalizations and drug dispensing from pharmacies. Multivariable Cox regression models adjusted for age, sex, calendar year, comorbidity, and concomitant pharmacotherapy were used to assess differences in the composite endpoint of non-fatal MI and cardiovascular mortality between individual GLDs, using metformin monotherapy as reference. Results The study comprised 9876 users of GLDs admitted with MI. The mean age was 72.3 years and 56.5% of patients were men. A total of 3649 received sulfonylureas and 711 received metformin at admission. The average length of follow-up was 2.2 (SD 2.6 years. A total of 6,171 patients experienced the composite study endpoint. The sulfonylureas glibenclamide, glimepiride, glipizide, and tolbutamide were associated with increased risk of cardiovascular mortality and/or nonfatal MI with hazard ratios [HRs] of 1.31 (95% confidence interval [CI] 1.17-1.46, 1.19 (1.06-1.32, 1.25 (1.11-1.42, and 1.18 (1.03-1.34, respectively, compared with metformin. Gliclazide was the only sulfonylurea not associated with increased risk compared with metformin (HR 1.03 [0.88-1.22]. Conclusions In patients with diabetes mellitus admitted with MI not treated with emergent percutaneous coronary

  17. Analysis on Use of Hypoglycemic Drugs in Our Hospital during 2008-2010%2008-2010年我院降血糖药物用药分析

    林国强; 沈斌


    Objective To investigate the current situation and the development trend of the hypoglycemic drugs used in our hospital to provide reference for the clinical application of antidiabetic drugs and its management. Methods The data of hypoglycemic drugs in the medical supply store were collected based on the used amount, defined daily dosages (DDDs) and the sums of money for statistical analysis during 2008 - 2010. Results The average annual increasing rate of the consumption amount of antidiabetic drugs was 40% during these three years. Acarbose occupied the first place in the list of the sum of consumption money and DDDs. Sulfonylureas and biguanides were most commonly used hypoglycemic drugs in clinic during successive 3 years, accounting for 32% of the total value of DDDs in whole antidiabetic drugs. The first line of antidiabetic drugs included metformin, gliclazide, acarbose, glipizide and insulin. Conclusion The used amounts of hypoglycemic drugs are gradually increased with the increase of diabetic patients year by year. Therefore, more attention should be paid to the curative effects and safety in medication.%目的 为降血糖药物的临床应用和管理提供参考.方法 对2008年至2010年医院药库出库的降血糖药物使用金额、用药频度(DDDs)、用药金额、各年度DDDs前10位药物等进行统计分析.结果 3年间降血糖药物销售金额年平均增长率为40%.销售金额及DDDs居首位的是阿卡渡糖,磺酰脲类和双胍类连续3年为临床主要使用的降血糖药物,占所有降血糖药物DDDs总值的32%;二甲双胍、格列齐特、阿卡波糖、格列美脲、胰岛素等为临床一线用药.结论 降血糖药物的用量随着糖尿病患者的增加逐年增长,因此临床用药应注意药物疗效及安全性.

  18. The use of sulphonylureas in the elderly.

    Graal, M B; Wolffenbuttel, B H


    damaging in the elderly. It has been associated primarily with long-acting sulphonylureas, like chlorpropamide and glibenclamide (glyburide). Hypoglycaemic episodes may trigger serious events like myocardial infarction or stroke. Therefore, shorter-acting compounds like tolbutamide and gliclazide have been relatively well tolerated and appear to be the best choice to treat elderly patients. It is advisable to start with a low dose and increase the dose, when needed, in small steps. The efficacy of sulphonylureas is much greater when they are taken before a meal. Because of the fact that type 2 diabetes mellitus is a progressive disease, and residual beta-cell function decreases with time, insulin therapy may ultimately be warranted in a significant number of patients.

  19. Pharmacoeconomic analysis on six kinds of regimens using oral antidiabetic drugs in national essential medicines%国家基本药物中口服降糖药6种用药方案的药物经济学分析

    江丽欢; 陈月婵; 霍彩凤


      目的:运用药物经济学方法评价国家基本药物中口服降糖药的6种用药方案治疗2型糖尿病的药物经济学效果,为治疗2型糖尿病的药物选择提供参考。方法:将我院2011年3月–2012年8月在门诊治疗的300例2型糖尿病患者平均分为6组,每组50例,分别给予二甲双胍(A组),格列齐特缓释胶囊(B组),格列美脲(C组),二甲双胍+格列本脲(D组),二甲双胍+格列美脲(E组),二甲双胍+格列齐特缓释胶囊(F组)进行治疗。观察12周后空腹血糖、餐后2 h血糖及HbA1c,利用成本-效果分析方法,比较其药物经济学效果。结果:治疗12周后,A、B、C、D、E、F组的成本分别为70.56、198.24、136.08、42.84、171.36、233.52元;总有效率分别为86.0%、88.0%、88.0%、84.0%、94.0%、92.0%。经过成本-效果分析,D组C/E为51.00,最小,E组ΔC/ΔE值为12.85,A组ΔC/ΔE值为13.86。结论:从药物经济学的角度分析,D组治疗2型糖尿病方案最经济,但是E组疗效最佳,单一用药方案中A组是最佳选择,在临床治疗中应根据具体情况合理选择。%  Objective:To evaluate the pharmacoeconomic effect on the six kinds of regimens using oral antidiabetic drugs in national essential medicines for treating type 2 diabetes mellitus, and provide reference for drug choice. Methods:A total of 300 type 2 diabetic patients in outpatient of our hospital collected from March 2011 to August 2012 were assigned into 6 groups with 50 cases in each group. Metformin (group A), gliclazide sustained release tablets (group B), glimepiride (group C), metformin and glibenclamide (group D), metformin and glimepiride (group E) and metformin and gliclazide sustained release tablets (group F) were given in different groups, respectively. The treatment effect was observed 12 weeks later by evaluating fasting blood glucose, postprandial 2 h blood glucose and HbA1c

  20. Application Analysis of Oral Hypoglycemic Drugs in 34 Hospitals of Nanjing during 2011-2013%南京地区34家医院2011~2013年常用口服降糖药用药分析

    王璐璐; 刘慧


    Objective:To evaluate the utilization of oral hypoglycemic drugs in 34 hospitals of Nanjing to provide clinical reference for the drug rational use. Methods: According to the sales data of oral hypoglycemic drugs in 34 hospitals of Nanjing from 2011 to 2013,the utilization of oral hypoglycemic drugs was analyzed retrospectively in respect of consumption sum,DDDs and defined daily cost ( DDC) by daily dose limit analysis method. Results: The top 3 oral hypoglycemic drugs in the list of consumption sum were acarbose,glimepiride and metformin. In terms of DDDs,glimepiride, metformin and gliclazide ranked the top 3. The consumption sum and DDDs of oral hypoglycemic drugs were increased year by year in Nanjing. The ratio of serial number of consumption sum and DDDs was from 0. 3 to 2. 0. Conclusion: The demanded quantity of oral hypoglycemic drugs is increased year by year from 2011 to 2013. The application conforms to the safe, effective and economic principle. The drugs should be chosen according to the drug characteristics in order to improve the abnormal glucose metabolism and prevent and treat the complications.%目的::了解南京地区口服降糖药的应用近况和发展趋势,为临床合理使用口服降糖药提供参考。方法:根据长江流域医药情报研究所提供的南京地区2011~2013年口服降糖药的销售数据,采用限定日剂量分析法,对该地区34家医院近三年口服降糖药的销售金额、用药频度( DDDs)和限定日费用( DDC)等进行统计分析。结果:销售金额排名前三位的药物是阿卡波糖、格列美脲、二甲双胍,DDDs排名前三位的药物是格列美脲、二甲双胍、格列齐特,总销售金额和总DDDs均呈逐年增长趋势,销售金额与DDDs的序号比值在0.3~2.0之间。结论:2011~2013年南京地区口服降糖药需求量逐年增加,口服降糖药使用符合安全、有效、经济的用药原则,建议治疗时根据药物的特点进行选择,

  1. [A 50-year history of new drugs in Japan-the development and progress of anti-diabetic drugs and the epidemiological aspects of diabetes mellitus].

    Ozawa, Hikaru; Murai, Yuriko; Ozawa, Terutaka


    recombinant products prevailed throughout the 1990s. Human insulin analogues (i.e., Insulin lispro and Insulin aspart) appeared in 2001. These are applied for after-meal glycosmia owing to their ultrarapid onset of activity. Self-injection by DM patients was legalized in 1981. To make the infection technique sure and easy, cartridge (pen-type) and disposable kit-type needles were devised in the 1990s. 2) Oral hypoglycemic drugs: Instead of the exclusive parenteral usage of insulins, there was also demand for oral dosage forms. The first of the sulfonyrlurea (SU) group, BZ-55, was used for DM clinically in 1955 in Germany. But it was soon withdrawn because of its antibacterial action. This led to the development of various SU groups. Tolbutamide (1956), chlorpropamide (1959), acetohexamide (1964) and tolazamide (1961) were introduced to Japan as first-generation SUs. Then glyclopyramide (Kyorin, 1965), glybenclamide (1971), gliclazide (1984) and glimepiride (1999) appeared as the second-generation SUs. These were used orally for Type 2 diabetes. Biguanide (BG) group, phenformin HC1 (1959), metformin HC1 (1961) and buformin HC1 (1961) had also been in use by oral treatment of Type 2 diabetes. SU appears to act by increasing the sensitivity of b-cells, which secrete insulin. BG probably exerts by increasing glucose transport across the membranes of target organs. 3) New types of antidiabetic drugs: a-Glucosidase inhibitors (i.e., acarbose: Bayer, 1993; and voglibose: Takeda, 1994) act on hyperglycemia after meals by decreasing glucose absorption. Thiazolidinedione compounds, such as troglitazone (Sankyo, 1995) and pioglitazone HC1 (Takeda, 1994) act by increasing the insulin sensitivity of the target tissues. These are useful for Type 2 DM patients when SUs are ineffective. Nevertheless, troglitazone was discontinued in 2000 due to severe liver damage. Nateglinide (Ajinomoto Co., 1999), which is a D-phenylalanine derivative acting similar to SUs, is useful orally for after

  2. The choice of initial insulin treatment plan for type 2 diabetes mellitus patients with failure of oral hypoglycemic agents%2型糖尿病患者口服降血糖药失效后起始胰岛素治疗方案的选择

    石立; 李德; 杜云峰; 高剑波; 薛云; 杨科春; 陈丽叶; 成金罗; 叶新华


    Objective To investigate the insulin treatment plan after the failure of oral hypoglycemic agents for type 2 diabetes in China.Methods 180 patients with type 2 diabetes who failed to oral hypoglycemic drugs were randomly divided into three groups on average:A group (insulin glargine + metformin + gliclazide sustained-release tablets),B group (insulin aspart 3 0 + metformin) and C group (insulin glargine + metformin + insulin aspart).24 weeks later,the hypoglycemic effect and security were observed.Three years later,the compliance that patients used original treatment plan were observed.Results 24 weeks later,HbA1c of the three group significantly decreased compared with that before the study [A group:(7.3 ± 0.8) % vs.(10.2 ± 1.7) %;B group:(7.0 ± 0.8) % vs.(9.9 ± 1.5)%;C group:(6.9 ±0.7)% vs.(10.4 ± 1.8)%,all P <0.05].The incidence of hypoglycemia in C group (1.66 times · year-1 · people-1) was significandy higher than that in A group (1.04 times · year-1 · people-1) and B group (1.31 times · year-1 · people-1) (x2 =11.777,4.362,all P < 0.05).However,the daily average cost of the drug in the B group [(12.9 ± 3.0) yuan] was significantly lower than that in A group [(25.6 ± 3.8) yuan] and C group [(22.7 ± 4.7) yuan] (t =18.943,13.226,all P < 0.05).Three years later,the percentage of patients who used original treatment plan in the C group(40.0%) was significantly less than that in A group(68.0%) and B group (73.0%) (x2 =8.656,12.398,all P < 0.05).Conclusion Type 2 diabetic patients who failed to oral hypoglycemic agents,according to their own economic conditions,might choose aspart 30 or glargine.The hypoglycemic treatment of aspart 30 has better long term effect,lower costs and incidence of hypoglycemia,better compliance.%目的 探讨2型糖尿病患者口服降血糖药失效后的胰岛素治疗方案.方法 选择180例口服降糖药失效的2型糖尿病患者按数字表法随机分为三组:A组(60

  3. Effect of Kaiyu Qingwei Jianji on the morphometry and residual strain distribution of small intestine in experimental diabetic rats

    Sha, Hong; Zhao, Jing-Bo; Zhang, Zhi-Yuan; Zhou, Shui-Ping; Tong, Xiao-Lin; Zhuang, Feng-Yuan; Gregersen, Hans


    AIM: To investigate the effect of a Chinese medicine, Kaiyu Qingwei Jianji (KYQWJJ) used for diabetic treatment, on the morphometry and residual strain distribution of the small intestine in streptozotocin (STZ) -induced diabetic rats. Correlation analysis was also performed between the opening angle and residual strain with the blood glucose level. METHODS: Forty-two male Wistar rats weighing 220-240 g were included in this study. Thirty-two STZ-induced diabetic rats were subdivided into four groups (n = 8 in each group), i.e. diabetic control group (DM); high dose of KYQWJJ (T1, 36g/kg per day); low dose of KYQWJJ (T2, 17 g/kg per day) and Gliclazide (T3, 50 mg/kg per day). Another ten rats were used as non-diabetic control (CON). The medicines were poured directly into stomach lumen by gastric lavage twice daily. The rats of CON and DM groups were only poured the physiological saline. Blood glucose and plasma insulin levels were measured. Experimental period was 35 d. At the end of experiment, three 5-cm long segments were harvested from the duodenum, jejunum and ileum. Three rings of 1-2 mm in length for no-load and zero-stress state tests were cut from the middle of different segments. The morphometric data, such as the circumferential length, the wall thickness and the opening angle were measured from the digitized images of intestinal segments in the no-load state and zero-stress state. The residual strain was computed from the morphometry data. Furthermore, the linear regression analysis was performed between blood glucose level with morphometric and biomechanical data in the different intestinal segments. RESULTS: The blood glucose level of DM group was consistent 4-fold to 5-fold higher than those in CON group during the experiment (16.89 ± 1.11 vs 3.44 ± 0.15 mmol/L, P 0.05) was significantly lower than those in DM group. The plasma insulin levels of DM, T1, T2 and T3 groups were significantly lower than those in CON group (10.98 ± 1.02, 12.52 ± 1

  4. Effect of Kaiyu Qingwei Jianji on the morphometry and residual strain distribution of small intestine in experimental diabetic rats

    Hong Sha; Jing-Bo Zhao; Zhi-Yuan Zhang; Shui-Ping Zhou; Xiao-Lin Tong; Feng-Yuan Zhuang; Hans Gregersen


    AIM: To investigate the effect of a Chinese medicine,Kaiyu Qingwei Jianji (KYQWJJ) used for diabetic treatment, on the morphometry and residual strain distribution of the small intestine in streptozotocin (STZ)-induced diabetic rats. Correlation analysis was also performed between the opening angle and residual strain with the blood glucose level.METHODS: Forty-two male Wistar rats weighing220-240 g were included in this study. Thirty-two STZ-induced diabetic rats were subdivided into four groups(n = 8 in each group), i.e. diabetic control group (DM);high dose of KYQWJJ (T1, 36g/kg per day); low dose of KYQWJJ (T2, 17 g/kg per day) and Gliclazide (T3,50 mg/kg per day). Another ten rats were used as nondiabetic control (CON). The medicines were poured directly into stomach lumen by gastric lavage twice daily.The rats of CON and DM groups were only poured the physiological saline. Blood glucose and plasma insulin levels were measured. Experimental period was 35 d.At the end of experiment, three 5-cm long segments were harvested from the duodenum, jejunum and ileum. Three rings of 1-2 mm in length for no-load and zero-stress state tests were cut from the middle of different segments. The morphometric data, such as the circumferential length, the wall thickness and the opening angle were measured from the digitized images of intestinal segments in the no-load state and zerostress state. The residual strain was computed from the morphometry data. Furthermore, the linear regression analysis was performed between blood glucose level with morphometric and biomechanical data in the different intestinal segments.RESULTS: The blood glucose level of DM group was consistent 4-fold to 5-fold higher than those in CON group during the experiment (16.89 ± 1.11 vs 3.44 ±0.15 mmol/L, P < 0.001). The blood glucose level in the T1 (16.89 ± 1.11 vs 11.08 ± 2.67 mmol/L, P < 0.01)and T3 groups (16.89 ± 1.11 vs 13.54 ± 1.73 mmol/L, P< 0.05), but not in T2 group (P > 0.05) was