- Binding studies based on ultrafast affinity extraction and single- or two-column systems: Interactions of second- and third-generation sulfonylurea drugs with normal or glycated human serum albumin. [Journal Article]
- JCJ Chromatogr B Analyt Technol Biomed Life Sci 2018 Dec 01; 1102-1103:8-16
- Ultrafast affinity extraction was evaluated and used with microcolumns containing human serum albumin (HSA) to measure the global affinity constants and dissociation rate constants for several second...
Ultrafast affinity extraction was evaluated and used with microcolumns containing human serum albumin (HSA) to measure the global affinity constants and dissociation rate constants for several second- and third-generation sulfonylurea drugs with solution-phase normal HSA or glycated HSA. Glibenclamide, glimepiride and glipizide were used as model drugs for this work. Both single- and two-column systems were considered for the analysis of global affinities for the model drugs. These methods were optimized with respect to the flow rates, column sizes and sample residence times that were employed with each drug for ultrafast affinity extraction. Data acquired with single-column systems were further utilized to estimate the dissociation rate constants for normal HSA and glycated HSA with the given drugs. The binding constants obtained by the single- and two-column systems showed good agreement with each other and with values obtained from the literature. Use of a single-column system indicated that levels of glycation found in controlled or advanced diabetes resulted in a 18-44% decrease in the overall binding strength of the model drugs with HSA. Although the two-column system allowed work with smaller free drug fractions and clinically-relevant drug/protein concentrations, the single-column system required less protein, provided better precision, and was easier to use in binding studies.
- Teneligliptin versus sitagliptin in Korean patients with type 2 diabetes inadequately controlled with metformin and glimepiride: A randomized, double-blind, non-inferiority trial. [Journal Article]
- DODiabetes Obes Metab 2018 Oct 26
- CONCLUSIONS: Teneligliptin was non-inferior to sitagliptin in the context of triple therapy for T2DM and is an important option in this setting (NCT02567994). This article is protected by copyright. All rights reserved.
- Pharmacokinetics and pharmacodynamics of glimepiride polymorphs. [Journal Article]
- IJInt J Pharm 2018 Oct 23; 553(1-2):272-280
- Glimepiride (GLIM) is used as an oral antihyperglycemic agent for treatment of type 2 diabetes. The drug presents two polymorphic forms (GLIM form I and GLIM form II) described in the literature, and...
Glimepiride (GLIM) is used as an oral antihyperglycemic agent for treatment of type 2 diabetes. The drug presents two polymorphic forms (GLIM form I and GLIM form II) described in the literature, and according to in vitro data, GLIM form II is about 3.5 times more soluble and releases 2 times the drug amount than GLIM form I in the physiological pH range. Considering the literature in vitro data and that the diabetes treatment demands glycemic control, avoiding abrupt fluctuations in the blood glucose levels, this work aimed to study the impact of GLIM polymorphism in the in vivo performance of GLIM solid oral dosages. For this, hard gelatin capsules with GLIM form I or II were prepared and orally administered in rats. After that, pharmacokinetic studies were performed by sampling animal blood at different times, and biochemical parameters (pharmacodynamic), such as glucose and insulin, were also evaluated. Our results showed that the in vitro data corroborate with our in vivo assays. GLIM form II provided higher plasma concentration of drug than form I (at baseline up to approximately 200 min after oral administration) and, consequently, increased insulin release and reduced levels of glucose, showing good correlation between pharmacokinetic and pharmacodynamics assays. Thus, this study demonstrated that GLIM polymorphs in oral dosages might alter the drug efficacy, which may expose the patients to risks, such as hypoglycemia.
- Sulfonylureas at the Glomerular Battlefield. [Editorial]
- EEEur Endocrinol 2018; 14(2):15-17
- The kidney is important in the context of diabetes not only because it is involved in normal glucose homeostasis, but also because it is one of the most important end organs to be involved in diabete...
The kidney is important in the context of diabetes not only because it is involved in normal glucose homeostasis, but also because it is one of the most important end organs to be involved in diabetes complications. Glomeruli are the meeting point of both microvascular, or renal; and macrovascular, or cardiovascular, health in diabetes. Sulfonylureas are effective glucose-lowering drugs. While a sulfonylurea-based glucose-lowering strategy is nephro-safe and nephro-protective, this aspect of sulfonylurea pharmaco-biology has not been highlighted earlier. In this editorial, we discuss current preclinical and clinical trial evidence regarding the performance of modern sulfonylureas at the glomerular battlefield.
- Effects of Repaglinide Versus Glimepiride on 1,5-Anhydroglucutol and Glycated Hemoglobin Levels in Japanese Patients With Type 2 Diabetes. [Journal Article]
- JCJ Clin Med Res 2018; 10(11):838-842
- CONCLUSIONS: Compared with glimepiride, repaglinide improved 1,5-anhydroglucitol levels but had no effect on glycated hemoglobin. This suggests that repaglinide is a useful option for treating postprandial hyperglycemia.
- Screening of HNF1A and HNF4A mutation and clinical phenotype analysis in a large cohort of Chinese patients with maturity-onset diabetes of the young. [Journal Article]
- ADActa Diabetol 2018 Oct 06
- CONCLUSIONS: The prevalence of HNF1A mutation was relatively lower in Mainland China and HNF4A mutation was rare. Serum hsCRP concentrations performed well in discriminating MODY3 from T2DM. Molecular diagnosis of MODY3/1 did transform management in clinical practice and facilitated the glycemic control.
- Glimepiride monotherapy versus combination of glimepiride and linagliptin therapy in patients with HNF1A-diabetes: a protocol for a randomised, double-blinded, placebo-controlled trial. [Journal Article]
- BOBMJ Open 2018 Oct 03; 8(10):e022517
- Hepatocyte nuclear factor 1α (HNF1A)-diabetes is the most common monogenetic subtype of diabetes. Strict glycaemic control is crucial for a good prognosis for patients with HNF1A-diabetes. Sulfonylur...
Hepatocyte nuclear factor 1α (HNF1A)-diabetes is the most common monogenetic subtype of diabetes. Strict glycaemic control is crucial for a good prognosis for patients with HNF1A-diabetes. Sulfonylurea (SU) is used as a first-line therapy in HNF1A-diabetes. However, SU therapy may be problematic as it confers a high risk of hypoglycaemia. We hypothesise that low dose of SU in combination with a dipeptidyl peptidase 4 inhibitor provides a safer and more efficacious treatment in patients with HNF1A-diabetes compared with SU as monotherapy.
- Successful switching from insulin to sulfonylurea in a 3-month-old infant with diabetes due to p.G53D mutation in KCNJ11. [Journal Article]
- APAnn Pediatr Endocrinol Metab 2018; 23(3):154-157
- Permanent neonatal diabetes mellitus is most commonly caused by mutations in the ATP-sensitive potassium channel (KATP) subunits. Prompt initiation of sulfonylurea treatment can improve glycemic cont...
Permanent neonatal diabetes mellitus is most commonly caused by mutations in the ATP-sensitive potassium channel (KATP) subunits. Prompt initiation of sulfonylurea treatment can improve glycemic control in children with KCNJ11 mutation. In this report, we present a case of permanent neonatal diabetes caused by a mutation in the KCNJ11 gene that was successfully treated via early switching of insulin to sulfonylurea treatment. A 53-day-old female infant presented with diabetic ketoacidosis. Insulin was administered for the ketoacidosis and blood glucose regulation. At 3 months of age, using genomic DNA extracted from peripheral lymphocytes, direct sequencing of KCNJ11 identified a heterozygous mutation of c.158G>A (p.G53D) and confirmed the diagnosis of permanent neonatal diabetes mellitus. Subsequently, treatment with sulfonylurea was initiated, and the insulin dose was gradually tapered. At 4 months of age, insulin therapy was discontinued, and sulfonylurea (glimepiride, 0.75 mg/kg) was administered alone. At 6 months after initiation of administration of sulfonylurea monotherapy, blood glucose control was stable, and no hypoglycemic events or developmental delays were reported. C-peptide levels increased during treatment with sulfonylurea. Early switching to sulfonylurea in infants with permanent diabetes mellitus owing to a KCNJ11 mutation could successfully help regulate glycemic control, which suggests the need for early genetic testing in patients presenting with diabetes before 6 months of age.
- The relationship between obesity, glycemia and leptin level of type 2 diabetes mellitus patients with metabolic syndrome. [Journal Article]
- WLWiad Lek 2018; 71(6):1165-1168
- CONCLUSIONS: Conclusions: The survey examined leptin level and showed that leptin level increases alongside with the disease duration. Consequently, insulin resistance index HOMA is associated with leptin resistance and there is a direct correlation between them.
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- New in-situ gelling biopolymer-based matrix for bioavailability enhancement of glimepiride; in-vitro/in-vivo x-ray imaging and pharmacodynamic evaluations. [Journal Article]
- PDPharm Dev Technol 2018 Sep 27; :1-11
- Glimepiride (Gmp) a third generation of sulphonylurea is a weakly acidic hypoglycemic drug that belongs to Biopharmaceutical Classification System (BCS) class II. It suffers from poor solubility as w...
Glimepiride (Gmp) a third generation of sulphonylurea is a weakly acidic hypoglycemic drug that belongs to Biopharmaceutical Classification System (BCS) class II. It suffers from poor solubility as well as erratic and variable therapeutic effect. The authors investigated the feasibility of utilizing two nontoxic and biodegradable biopolymers (casein (CA) and chitosan (CT)) as a new in-situ gelling tablet matrix to circumvent this limitation. Both polymers in different ratios were combined with constant dose of the drug and compressed by direct compression to produce constant weights of different tablet matrices. Basic tromethamine (Tris) was also included in each matrix as a pH modifier. Swelling indices, rheological properties of the swollen matrices, and their in-vitro drug release in simulating gastric fluid were assessed. The higher the ratio of casein in the tablet matrix, the lower its swelling index and the higher its viscosity indicate a shear thickening property. Intuitively, zero order drug diffusion in 0.1 N HCl prevailed for more than 8 hours from this gelled matrix. Both reduction of blood glucose level up till 11 hours and x-ray imaging of the selected tablets in the GIT of rabbits correlated well with the shear thickening properties. These findings propose a new stable, simple and affordable price matrix with large versatility.