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Zheng Lu, Yonglai Yang, Rae-Ann Covington, Yunxia Vivian Bi, Thomas Dürig, Reza Fassihi
The aim of this study was to develop a hydrophilic oral controlled release system (CRS) using the amorphous form of gliclazide, a BCS class II compound, listed on the WHO list of essential medicines. For this purpose, spray-dried dispersions (SDDs) of gliclazide were produced using various grades of hydroxypropyl methylcellulose acetate succinate (HPMCAS) or copovidone as carrier under fully automated conditions. The solid-state properties of prepared SDDs were characterized using X-ray powder diffraction (XRPD), scanning electron microscopy (SEM), modulated differential scanning calorimetry (MDSC), and Fourier transform infrared spectroscopy (FTIR)...
October 6, 2016: AAPS PharmSciTech
Qing Li, Ting-Ting Tang, Feng Jiang, Rong Zhang, Miao Chen, Jun Yin, Yu-Qian Bao, Xiang Cheng, Cheng Hu, Wei-Ping Jia
AIM: KCNQ1 channel is a member of the voltage-gated potassium channel KQT-like subfamily. The KCNQ1 gene has recently been identified as a susceptibility locus for type 2 diabetes mellitus (T2DM). In the present study, we examined the effects of KCNQ1 variants on the therapeutic response to modified-release gliclazide (gliclazide MR) treatment in Chinese patients newly diagnosed with T2DM. METHODS: A total of 100 newly diagnosed T2DM patients without a history of any anti-diabetic medications were treated with gliclazide MR for 16 weeks, but 91 patients completed the entire study...
October 3, 2016: Acta Pharmacologica Sinica
V Mohan, V Chopra, D Sanyal, S Jain, J Jayaprakashsai
OBJECTIVE: This study examines whether a new, scored and breakable once daily gliclazide tablet formulation, gliclazide XR 60 mg, that enables a simple 2-steps titration, can improve glycemic control rates in the community. METHODS: In a prospective multicenter study of 4 months duration, organised in the primary care setting of urban India, type 2 diabetes patients, uncontrolled with diet alone or metformin monotherapy, received 1 (60 mg), 1½ (90 mg), or 2 (120 mg) tablets of gliclazide XR 60 mg to achieve a target fasting plasma glucose of 126 mg/dl, or HbA1c of 7%...
December 2015: Journal of the Association of Physicians of India
S K Bajpai, Navin Chand, Seema Tiwari, Shweta Soni
In this study, dextran (Dex) has been cross-linked with epichlorohydrin (Ech) to yield cross-linked hydrogels. These gels were characterized by Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD) analysis, Thermogravimetric analysis (TGA), and Scanning electron microscopy (SEM). The water absorption behavior of gels was studied in simulating gastric fluid (SGF) and simulating intestinal fluid (SIF) at 37°C. The data was interpreted by various kinetic models. The swelling was found to be totally diffusion controlled...
September 21, 2016: International Journal of Biological Macromolecules
Rimke C Vos, Mariëlle Jp van Avendonk, Hanneke Jansen, Alexander N Goudswaard, Maureen van den Donk, Kees Gorter, Anneloes Kerssen, Guy Ehm Rutten
BACKGROUND: It is unclear whether people with type 2 diabetes mellitus on insulin monotherapy who do not achieve adequate glycaemic control should continue insulin as monotherapy or can benefit from adding oral glucose-lowering agents to the insulin therapy. OBJECTIVES: To assess the effects of insulin monotherapy compared with the addition of oral glucose-lowering agents to insulin monotherapy for people with type 2 diabetes already on insulin therapy and inadequate glycaemic control...
September 18, 2016: Cochrane Database of Systematic Reviews
Harilal Patel, Poonam Giri, Nuggehally R Srinivas
Goto-Kakizaki (GK) rats represent a unique non-obese and lean model with manifestation of type 2 diabetes (T2DM) broadly mimicking the human T2DM development. Therefore, in addition to the use of GK rats to test the efficacy of drugs, it may represent a great tool to study the influence of altered physiological process and/or organ specific pathophysiological changes (i.e., liver, kidney, etc.) on the disposition of drugs. The objectives of the review were: (a) to compile the published pharmacokinetic data of several drugs, such as cephalexin, cyclosporine, exendin-4, gliclazide, grepafloxacin, rosuvastatin, salsalate, salicylic acid, and theophylline, in GK rats relative to normal rats; and (b) critically evaluate the possible role of physiologically altered processes on the pharmacokinetics of reviewed drugs...
September 13, 2016: European Journal of Drug Metabolism and Pharmacokinetics
Amal M Mahfoz, Hekma A Abd El-Latif, Lamiaa A Ahmed, Nahed M Hassanein, Afaf A Shoka
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...
September 9, 2016: Naunyn-Schmiedeberg's Archives of Pharmacology
Alla K Ovsyannikova, Oksana D Rymar, Elena V Shakhtshneider, Vadim V Klimontov, Elena A Koroleva, Natalya E Myakina, Mikhail I Voevoda
Maturity-onset diabetes of the young (MODY) is a heterogeneous group of diseases associated with gene mutations leading to dysfunction of pancreatic β-cells. Thirteen identified MODY variants differ from each other by the clinical course and treatment requirement. Currently, MODY subtypes 1-5 are best-studied, descriptions of the other forms are sporadic. This article reports a MODY12 clinical case, caused by a mutation in the gene of the ATP-binding cassette transporter sub-family C member 8 (ABCC8), encoding sulfonylurea receptor 1...
September 2016: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
Mehran Mesgari Abbasi, Hadi Valizadeh, Hamed Hamishehkar, Parvin Zakeri-Milani
P-glycoprotein (P-gp) is a trans-membrane drug efflux pump. Several drugs are P-gp substrates. Some drugs may affect the activity of P-gp by inhibiting its function, resulting in significant drug-drug interactions (DDIs). It is critical to understand which drugs are inhibitors of P-gp so that adverse DDIs can be minimized or avoided. This study investigated the effects of gliclazide, metformin, and pioglitazone on the function and expression of P-gp. Rhodamine 123 (Rh 123) efflux assays in Caco-2 cells and western blot testing were used to study in vitro the effect of the drugs on P-gp function and expression...
May 2016: Research in Pharmaceutical Sciences
Hongping Yao, Juanyi Feng, Qiaowei Zheng, Youxia Wei, Shixiang Wang, Weiyi Feng
AIMS: This study investigated the efficacies of gliclazide (GLZ), methylcobalamin (MCA), and GLZ+MCA combination therapy on DPN by evaluating the treatment-related changes in peripheral nerve function, the polyol pathway, and oxidative stress in the sciatic nerve of streptozotocin-induced diabetic rats. MATERIALS AND METHODS: The rat model of streptozotocin-induced diabetes was orally given GLZ (25mg/kg/day), MCA (175μg/kg/day), and GLZ+MCA (25mg/kg/day+175μg/kg/day) combination therapy for 8weeks, in order to observe its effects on the motor nerve conduction velocity (MNCV), on the activities of Na(+), K(+)-ATPase, aldose reductase(AR), AR mRNA expression, on the polyol contents, antioxidative enzyme activities and peroxidation products in the sciatic never tissue...
September 15, 2016: Life Sciences
Anna J Anderson, Ruth Andrew, Natalie Z Homer, Gregory C Jones, Kenneth Smith, Dawn E Livingstone, Brian R Walker, Roland H Stimson
CONTEXT: The mechanism of action of metformin remains unclear. Given the regulation of the cortisol-regenerating enzyme 11βhydroxysteroid dehydrogenase 1 (11βHSD1) by insulin and the limited efficacy of selective 11βHSD1 inhibitors to lower blood glucose when co-prescribed with metformin, we hypothesized that metformin reduces 11βHSD1 activity. OBJECTIVE: To determine whether metformin regulates 11βHSD1 activity in vivo in obese men with and without type 2 diabetes mellitus...
October 2016: Journal of Clinical Endocrinology and Metabolism
S E Andersen, M Christensen
AIMS/HYPOTHESIS: The risk of hypoglycaemia may differ among sulphonylureas (SUs), but evidence from head-to-head comparisons is sparse. Performing a network meta-analysis to use indirect evidence from randomised controlled trials (RCTs), we compared the relative risk of hypoglycaemia with newer generation SUs when added to metformin. METHODS: A systematic review identified RCTs lasting 12-52 weeks and evaluating SUs added to inadequate metformin monotherapy (≥1000 mg/day) in type 2 diabetes...
July 18, 2016: British Journal of Clinical Pharmacology
Judith van Dalem, Martijn C G J Brouwers, Coen D A Stehouwer, André Krings, Hubert G M Leufkens, Johanna H M Driessen, Frank de Vries, Andrea M Burden
OBJECTIVE:  To determine the association between use of sulphonylureas and risk of hypoglycaemia in relation to renal function and sulphonylurea metabolic group compared with use of metformin. DESIGN:  Population based cohort study using routinely collected data from general practices in England. SETTING:  Clinical Practice Research Datalink (CPRD) database, 2004-12. PARTICIPANTS:  120 803 new users of a non-insulin antidiabetic agent with at least one prescription and aged 18 years or more...
2016: BMJ: British Medical Journal
Hiroshi Kamiyama, Kazutaka Aoki, Shigeru Nakajima, Kazuaki Shinoda, Kazunari Kamiko, Masataka Taguri, Yasuo Terauchi
Objective Switching from sulfonylureas to repaglinide in patients with type 2 diabetes improves glycemic control; however, the optimal dosage has not been fully evaluated. We designed to show that repaglinide was equivalent to sulfonylurea in Japanese patients with type 2 diabetes. We herein evaluated whether we could switch from sulfonylureas to repaglinide twice or thrice daily in Japanese adult patients who had been treated with anti-diabetic drugs, including sulfonylureas, and whose conditions were moderately well-controlled...
2016: Internal Medicine
Parim Brahma Naidu, V V Sathibabu Uddandrao, Ramavat Ravindar Naik, Suresh Pothani, Praveen Kumar Munipally, Balaji Meriga, Mustapha Sabana Begum, Chandrasekar Varatharaju, Rajesh Pandiyan, Ganapathy Saravanan
OBJECTIVES: We evaluated the effects of S-allylcysteine (SAC) on biomarkers of the polyol pathway in streptozotocin-nicotinamide (STZ-NA)-induced diabetes in rats. METHODS: Diabetes was induced in male albino Wistar rats by intraperitoneal administration of STZ (55 mg kg(-1) bw(-1)) and NA (110 mg kg(-1) bw(-1)). SAC (150 mg kg(-1) bw(-1)) was orally administered to the rats with diabetes for 45 days to assess its effects on blood glucose, insulin, insulin resistance, glycated hemoglobin, aldose reductase (AR), sorbitol dehydrogenase (SDH), sorbitol, fructose, thiobarbituric acid-reactive substances (TBARS), hydroperoxide, hemoglobin and glutathione (GSH)...
July 1, 2016: Canadian Journal of Diabetes
Kelly Etherson, Gavin Halbert, Moira Elliott
OBJECTIVES: The aim of this study was to determine the influence of non-ionisable excipients hydroxypropyl-β-cyclodextrin (HPβCD) and poloxamers 407 and 188 on the supersaturation and precipitation kinetics of ibuprofen, gliclazide, propranolol and atenolol induced through solution pH shifts using the CheqSol method. METHODS: The drug's kinetic and intrinsic aqueous solubilities were measured in the presence of increasing excipient concentrations using the CheqSol method...
September 2016: Journal of Pharmacy and Pharmacology
Dennis Schrijnders, Laura C Hartog, Nanne Kleefstra, Klaas H Groenier, Gijs W D Landman, Henk J G Bilo
BACKGROUND: 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...
2016: PloS One
Sally A El Awdan, Gehad A Abdel Jaleel, Dalia O Saleh, Marawan Abdel Basset, Farouk R Melek, Iman A A Kassem, Manal Badawi
The fruits of Gleditsia species (Fabaceae) have been known in traditional medicine as a saponin-rich herbal medicine. The present study aimed to investigate the effects of the total methanolic extract of Gleditsia caspica (MEGC) and its saponin-containing fractions (SFGC) on hyperglycemia in streptozotocin (STZ)-induced diabetic rats. A single intraperitoneal injection of STZ (55 mg/kg body weight) was used to induce hyperglycemia in male albino rats. MEGC (15, 30 and 60 mg/kg, p.o.) and SFGC (15, 30 and 60 mg/kg, p...
2016: Zeitschrift Für Naturforschung. C, A Journal of Biosciences
Xiaopeng Han, Wei Wei, Lu Zhong, Cong Luo, Chunnuan Wu, Qikun Jiang, Jin Sun
An efficient extraction of doxorubicin (Dox) from homemade stealth hyalurionic acid (HA)-based nanoparticles (NPs) in rat plasma could not be performed by previously published methods. Therefore, we attempted to establish the novel NPs-breaking and UPLC-MS-MS method for evaluating the pharmacokinetic profiles of the homemade stealth HA NPs in rats. The pretreatment method of plasma samples used the liquid-liquid extraction method with isopropyl alcohol as NPs-breaking and protein-precipitating solvents, and the NPs-breaking efficiency of isopropyl alcohol was as high as 97...
September 2016: Journal of Chromatographic Science
Oleksii M Antypenko, Sergiy I Kovalenko, Galina O Zhernova
Methods of 1-[2-(1H-tetrazol-5-yl)-R(1)-phenyl]-3-R(2)-phenyl(ethyl)ureas and R(1)-tetrazolo[1,5-c]quinazolin-5(6H)-ones synthesis were designed. IR, LC-MS, (1)H NMR, and elemental analysis data evaluated the structure and purity of the obtained compounds. Different products, depending on the reaction conditions, were distinguished and discussed. The preliminary hypoglycemic activity of 36 synthesized compounds was revealed. Docking studies to 11β-hydroxysteroid dehydrogenase 1, γ-peroxisome proliferator-activated receptor, and dipeptidyl peptidase-4 were conducted...
April 2016: Scientia Pharmaceutica
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