Dose Of Glibenclamide Research Articles

Novel Perspectives of Super-High Dose Glybenclamide in an Infant With DEND Syndrome

Mutations in KCNJ11 gene cause a variety of persistent neonatal diabetes mellitus syndromes (PNDM), with and without developmental delay and epilepsy presentations (developmental delay, epilepsy, and neonatal diabetes - DEND Syndrome). We report a heterozygous mutation for pathogenic KCNJ11 missense variant: c.190G>A, p. (Val64Met), reported once so far, associated with severe epilepsy and neurological deterioration phenotype, responsive to a combination of super high doses of Glibenclamide (Sulfonylurea) and oral steroids. We had the patient attached to continuous glucose monitoring, performed electroencephalogramic tracings, magnetic resonance imaging and whole exome sequencing on parents and patient DNA and Sanger sequencing (SS) on candidate gene mutations. His phenotypic description and management during 18 months, demonstrates this mutation is responsive to super-high doses of SU combined with high dose 6 weeks steroids protocol. In conclusion, we have identified a de novo heterozygous missense mutation as the etiology for severe DEND syndrome in a one day old neonate, presenting with asymptomatic hyperglycemia, responsive to a novel management combination.

Glibenclamide Advantage in Treating Edema After Intracerebral Hemorrhage (GATE-ICH): Study Protocol for a Multicenter Randomized, Controlled, Assessor-Blinded Trial.

Introduction: Brain edema after acute intracerebral hemorrhage (ICH) plays a critical role in the secondary injury of ICH and may heighten the potential for a poor outcome. This trial aims to explore the efficacy of small doses of oral glibenclamide in perihematomal edema (PHE) and the prognosis of patients with ICH.Methods and Analysis: The GATE-ICH trial is a multicenter randomized, controlled, assessor-blinded trial. A total of 220 adult patients with acute primary ICH in 28 study centers in China will be randomized to the glibenclamide group (glibenclamide plus guideline-recommended ICH management) or the control group (guideline-recommended ICH management). Multivariate logistic regression will be used to analyze the relationship between the treatments and primary outcome.Study Outcomes: The primary efficacy outcome is the proportion of poor functional outcomes (modified Rankin Scale ≥3) at 90 days after enrollment. The secondary efficacy outcomes include changes in the volume of ICH and PHE between the baseline and follow-up computed tomography scans as well as the clinical scores between the baseline and follow-up assessments.Discussion: The GATE-ICH trial will assess the effects of small doses of oral glibenclamide in reducing the PHE after ICH and improving the 90-day prognosis of patients.Clinical Trial Registration: www.clinicaltrials.gov., NCT03741530. Registered on November 8, 2018.Trial Status: Protocol version: May 6, 2019, Version 5. Recruitment and follow-up of patients is currently ongoing. This trial will be end in the second quarter of 2021.

Extracts of Ficusgibboseblame and its potentiating effect for type II diabetes in rats

HydroalcoholicextractofGreeneriesandstalkbarkofFicusgibbosaBlume is evaluated for their potentiating action in Streptozotocin – Nicotinamide encouraged type 2 diabetes in Sprague Dawley rats. The excerpts are managed at the amount of 100, 250 and 500 mg/kg body weight along with sub operative dose (2.5 mg/kg body weight) of the standard antidiabetic drug (Glibenclamide) for a period of 5 weeks. The test extracts potentiated the antidiabetic activity of standard drug by significantly dropping the raised blood glucose levels and the effect was almost comparable with solitary efficacy of therapeutic dose (5 mg/kg body weight) of typical drug Glibenclamide during 5th week of the study. Its abandons have deviated, on the other hand, orchestrated and more gibbose in those end. The juice of the bark furthermore abandons from claiming color fig alternately bumped fig plant is utilized to grinding those pills furthermore settling on A decoction in toxicology. Plant appeases diminished Kapha, pitta, skin diseases, ulcers, hepatopathy, diabetes, ulcerative stomatitis, leucorrhoea and gynaecological issues. Male Sprague Dawley Rats abstainedinstantare vaccinated intraperitoneally with result about Nicotinamide at a dosage of 195 mg /kg body weight. 15 minutes after same animals are vaccinated for the newly readied result from claiming Streptozotocin (STZ) In measurement about (65 mg/kg physique weight) intraperitoneally. The animals are permitted to drink 1% glucose result instant will succeed the pill prompted hypoglycaemia.

The Effect of CYP2C9 Genotype Variants in Type 2 Diabetes on the Pharmacological Effectiveness of Sulfonylureas, Diabetic Retinopathy, and Nephropathy.

AimType 2 diabetes (T2D), as a major cause of morbidity and mortality, is predicted to have a prevalence of 629 million by 2045. As diabetic patients show considerable inter-individual variation in response to antidiabetic treatment, this study aimed to investigate the gene polymorphism of cytochrome P450 as well as the effectiveness and safety of glibenclamide and gliclazide for different genotypes of CYP2C9. Besides, the chronic side effects of T2D including retinal microvasculature complications or retinopathy and renal dysfunction due to nephropathy in different genotypes were considered.Patients and MethodsThe participants including 80 T2D patients treated with glibenclamide or gliclazide were recruited from university hospitals of Ahvaz Jundishpur University of Medical Sciences, Ahvaz, in the southwest of Iran. Blood samples were collected from the patients at 2.5h after the morning dose of glibenclamide and 12h after the last dose of gliclazide. Genotyping from the extracted DNA was, then, performed using PCR-RFLP. The plasma level of glibenclamide and gliclazide was, in turn, measured by the reverse-phase high-pressure liquid chromatography.ResultsThe results showed that the wild-type allele, i.e., CYP2C9*1, occurred in the highest frequency (0.8), while the frequency rates of the mutant allele, i.e., CYP2C9*2 and CYP2C9*3, were 0.15 and 0.05, respectively. Moreover, no significant association was found between any of the genotypes as well as the clinical and biochemical characteristics of the patients. The findings also showed that the plasma level of sulfonylureas (i.e., glibenclamide and gliclazide) was the highest in the patients with the CYP2C9*3 allele. It was also found that 75.9% of the patients with variant genotypes had experienced hypoglycemia events. Furthermore, in the absence of wild type allele, a significant increase was observed in retinopathy (p=0.039) and nephropathy (p=0.05).ConclusionThe findings can provide guidelines for the optimal management of the treatment protocols with sulfonylurea intended to control the T2D complications.

Polymeric Microparticles as Alternative Carriers for Antidiabetic Glibenclamide Drug

Background: Glibenclamide is a lipophilic drug widely used in type 2 diabetes treatment. However, its low bioavailability limits its use. Thus, novel formulations should be applied to improve the drug’s bioavailability.
 Objectives: This study aimed to develop alternative carriers for oral delivery of glibenclamide. For this purpose, two biocompatible polymers, poly(e-caprolactone) and poly(butylene adipate) were formulated as microparticles (MPs) capable of loading the antidiabetic drug.
 Methods: In this regard, as microparticle fabrication approach, the modified emulsion solvent evaporation method was applied. Physicochemical evaluation of the prepared microparticles included the examination of their morphology, degradation rate, and thermal properties. Drug entrapment, drug loading, and particle size were also investigated. Simulated intestinal medium and body fluid at 37oC were selected as dissolution media. Differential scanning calorimetry was used to investigate the crystal properties of the microparticles and drugs.
 Results: The developed microparticles had sizes between 0.5 and 4 μm. Poly(butylene adipate) based microparticles had a smooth surface, whereas poly(ε-caprolactone) based microparticles showed a porous surface. The DSC thermogram revealed the amorphization of the drug. Hydrolysis results exhibited a very low mass loss, while in vitro release results depicted that the dissolution rate of the prepared microparticles was higher than that of pure glibenclamide demonstrating a prolonged pattern which is ideal for minimizing the daily dose of glibenclamide.
 Conclusion: In this study, novel carriers for glibenclamide were successfully prepared with promising future use.

Immunomodulatory and Anti-Diabetic Properties in Urine of Badri Cow

The current study was aimed to investigate the immunomodulatory and anti hyperglycemic activity of cow urine using Wistar albino rats as experimental animal model. Three doses of cow urine (2, 4 and 6 ml/kg body weight) were administered to rats and selected on the basis of random sampling method. Neutrophil adhesion and delayed hypersensitivity tests were done to assess the cellular immunity, whereas humoral immunity was investigated by indirect haemagglutination titer assay. Diabetes was induced in rats by the administration of alloxan (150 mg/kg, intraperitoneal). The effect of different doses of cow urine and Glibenclamide (standard drug) was observed for consecutive 3 w. At dose 4 and 6 ml/kg, a significant increase in neutrophil adhesion and delayed type hypersensitivity responses were observed. The circulating antibody titer was significantly increased in animals treated with 6 ml/kg. Surprisingly, cow urine resulted in the significant decline in blood sugar level of diabetic animals as compared to diabetic control group. This shows that Badri cow urine has potential to modulate immune system via cellular and humoral immune responses. The results also indicate the dose-dependent antidiabetic activity of Badri cow urine. Hence, it may be used as alternative medicine in the treatment of diabetes and other related manifestations

ANTIDIABETIC ACTIVITY TEST USING AMLA FRUIT (PHYLLANTHUS EMBLICA L) EXTRACT IN ALLOXAN-INDUCED BALB/C MICE

Background: The content of secondary metabolites in amla (phyllanthus emblica L.) such as flavonoids and phenols have the potential as an antioxidant. One of the benefits of antioxidants is to prevent degenerative diseases, such as diabetes mellitus. Purpose: This research to determine activity of amla fruit extract in reducing blood glucose levels at balb/c mice induced with alloxan. Methods. This research method uses a pre and posttest-controlled group design with 35 balb/c mice divided into five treatments groups. In the positive control group and the treatment group alloxan was injected for 14 days. Results: Amla (Phyllanthus emblica L.) fruit extract at a dose of 40 mg / 20 g BW was equivalent to positive control of glibenclamide dose 3 mg / 20 g BW compared to the treatment group at a dose of 10 mg / 20 g BW and 20 mg /20 g BW. Conclusion: From this research, it was obtained that the best dose of Amla fruit (phylanthus emblica L) extract applied to blood glucose was 40 mg/20mg BW with a decrease percentage of 56,93% with an effective dose value (ED50) 50% of 34.00 mg / 20 g BW.

The Improvement of INS Gene Sequences on Rat Model of Type 1 Diabetes in Goat Milk Casein Protein Treatment, but not in Glibenclamide

This study was aimed to determine the effect of CSN1S2 protein from Etawah Crossbred goat milk for repairing DNA sequence of INS gene in T1DM rat model. We divided the experimental rats into control group, diabetes group, control with CSN1S2 protein treatment group, diabetes with CSN1S2 protein treatment group, and diabetes with glibenclamide treatment group. The dose of CSN1S2 protein and glibenclamide used was 800 mg/kg BW and 5 mg/kg BW, respectively. We isolated the DNA from rat pancreas tissue and amplified it with a specific primer of INS gene. Our study investigated that there were transition, transversion, and deletion mutation in diabetic rat. The glibenclamide administration had changed 6 point mutations in INS of the diabetic rat to normal, but it created the other 9 new mutations. The CSN1S2 protein treatment showed mutation repairing in INS of diabetes group. Consequently, CSN1S2 have potential effect as anti-diabetes and is safe to consume than glibenclamide.

The combined effect of Trigonella foenum seeds and Coriandrum sativum leaf extracts in alloxan induced diabetes mellitus wister albino rats

Diabetes mellitus is a group of heterogeneous disorders commonly presenting with episodes of hyperglycemia and glucose intolerance, as a result of lack of insulin, ineffective insulin action, and/or both. It is our interest to study the effect of ethanolic extract of Trigonella foenum seeds (fenugreek) and Coriandrum sativum leaves (dhaniya) or its combination in alloxan induced diabetes mellitus wistar albino rats. Rats were randomly separated into six groups where group 1 animals received 2% acacia, group 2 animals received alloxan dose of 150 mg/kg, group 3 animals received glibenclamide dose of 0.5 mg/kg and group 4, 5 and 6 animals received ethanolic extracts of Trigonella foenum seeds, Coriandrum sativum leaves and combination of both extracts at the dose of 100mg/kg for 21 days. Different biochemical parameters such as hepatic and renal biomarkers and histopathology of pancreas were studied. Combination of both extracts showed significant decrease in blood glucose, cholesterol, triglycerides, LDL, VLDL levels, SGOT, SGPT, urea, creatinine and increase in HDL levels and body weight than individual extracts. Thus, we show the antidiabetic activity of poly herbal formulation using biochemical and histo pathological data.

UJI EFEKTIVITAS ANTIDIABETES KOMBINASI EKSTRAK DAUN MENIRAN (Phyllanthus niruri L.) Dan KELOPAK BUNGA ROSELLA (Hibiscus sabdariffa L.) PADA TIKUS JANTAN PUTIH

Purpose: To determine the effect of decreasing blood glucose levels in white rats using a combination of meniran and rosella compared to glibenclamide. Method: This research was carried out experimentally. Simplicia of meniran leaves and rosella macerated using 80% ethanol. The research used 21 rats that were induced by alloxan and divided into 7 groups and all compared using glibenclamide.Group 1 (negative control) CMC Na 1%, group 2 (positive control) glibenclamide dose 0.45 mg/kgMB, group 3 single roselle extract dose 130 mg/kgMB, group 4 single meniran leaf extract dose 200 mg/kgMB, group 5 combination of meniran leaf extract dose of 100 mg/kgMB and rosella extract dose of 65 mg/kgMB, group 6 combination of meniran leaf extract dose of 200 mg/kgMB and rosella extract dose of 130 mg/kgMB, and group 7 meniran leaf extract combination dose 400 mg/kgMB and rosella extract dose 195 mg/kgMB. Result: The results showed that rats had hyperglycemia after being induced by alloxan.Data were analyzed using one way ANOVA method followed by LSD and tukeys' B post hoct test. Having a difference in the decrease in blood glucose levels between the positive control group and the five doses of meniran extract and rosella gave a significant effect compared to the negative control group did not have a significant effect in reducing blood glucose levels. Conclusion: Single meniran extract and high-dose combination extract are more effective than glibenclamide.

Glibenclamide, a Sur1-Trpm4 antagonist, does not improve outcome after collagenase-induced intracerebral hemorrhage.

The sulfonylurea 1 transient receptor potential melastatin 4 (Sur1-Trpm4) receptor is selectively expressed after intracerebral hemorrhage (ICH). This upregulation contributes to increases in intracellular sodium. Water follows sodium through aquaporin channels, leading to cytotoxic edema. Even after edema is thought to have resolved, ionic dyshomeostasis persists, as does blood-brain barrier (BBB) damage. Glibenclamide, a hypoglycemic agent that inhibits Sur1-Trpm4, has been shown to reduce BBB damage and edema following infusion of autologous blood into the brain (ICH) as well as after other brain injuries. In order to further assess efficacy, we used the collagenase ICH model in rats to test whether glibenclamide reduces edema, attenuates ion dyshomeostasis, improves BBB damage, and reduces lesion volume. We tested a widely-used glibenclamide dose shown effective in other studies (10 μg/kg loading dose followed by 200 ng/hr for up to 7 days). Early initiation of glibenclamide did not significantly impact edema (72 hours), BBB permeability (72 hours), or lesion volume after ICH (28 days). Recovery from neurological impairments was also not improved by glibenclamide. These results suggest that glibenclamide will not improve outcome in ICH. However, the treatment appeared to be safe as there was no effect on bleeding or other physiological variables.

Effects of Fractionated Neem Leaf Extract (IRC) on Blood Glucose Level in Alloxan Induced Diabetic Wistar Rats

This study evaluated the hypoglycaemic effects of fractionated neem leaf extract (IRC) on alloxan induced diabetic wistar rats. IRC dissolved in phosphate buffered saline (PBS) PH 7.2 was administered as 50 mg/kg, 500 mg/kg, 1000 mg/kg, 2000 mg/kg single doses and 5 mg/kg, 50 mg/kg, 250 mg/kg and 500 mg/kg repeated doses in the diabetic rats while in the normoglycaemic rats 100 mg/kg and 250 mg/kg were used respectively. The positive control groups received single and repeated doses of glibenclamide (5 mg/kg) while the negative control groups were left untreated in each case. Single doses of the extract in diabetic wistar rats produced maximal dose dependent percentage reduction after 4 hours of administration with percentage reductions of 13.10% (500 mg/kg), 14.40% (1000 mg/kg) and 17.50% (2000 mg/kg) respectively. The result shows that 500mg/kg repeated doses gave the highest percentage reduction in fasting blood glucose in alloxan induced diabetic rats after 7, 14 and 21 days as follows 55%, 31.7% and 29.3% while 250 mg/kg repeated doses produced the highest percentage reduction of fasting blood glucose in non-diabetic rats at 7, 14 and 21 days and are 21.4%, 26.6%, 25.16% respectively. In conclusion, IRC lowered fasting blood glucose levels in non-diabetic and alloxan induced diabetic rats when given orally.

Evaluation of the pharmacological involvement of ATP-sensitive potassium (KATP) channels in the antidepressant-like effects of topiramate on mice.

Acute doses of topiramate (TPM) have been shown to reduce immobility time in the mice forced swimming test (FST) through inhibition of the nitric oxide (NO) pathway. Adenosine triphosphate-sensitive potassium (KATP) channels are known to have an active role in depression. This study investigates the potential participation of KATP channels in the antidepressant-like effect of TPM through the stimulatory effects of NO. FST and tail suspension tests (TST) were applied to adult male mice for assessment of the antidepressant-like activity of TPM. Different doses of glibenclamide and cromakalim were also applied in order to investigate the involvement of KATP channels. Fluoxetine was used as a positive control for evaluation of antidepressant-like effects. In addition, each animal's locomotor activity was evaluated by the open-field test (OFT). TPM (30mg/kg intraperitoneal (i.p.)) had a significant reductive effect on the immobility behavior similar to fluoxetine (20mg/kg). Co-administration of sub-effective doses of glibenclamide (1mg/kg i.p.) and TPM (10mg/kg i.p.) led to significant synergistic effects in FST and TST. Additionally, the results showed that administration of the sub-effective dose of cromakalim (0.1 and 0.3mg/kg i.p.) blocked the antidepressant-like effects of TPM (30mg/kg i.p.) in both tests. These interventions had no impact on the locomotor movement of mice in OFT. This study shows that the antidepressant-like activity of TPM may potentially be mediated by the blocking of the KATP channels.

The effect of jengkol (Archidendron pauciflorum) fruit peel ethanolic extract to heart histologic of rat induced by streptozotocin

Abadi SA, Illiyyin Z, Rachmadina JR, Malini DM. 2018. The effect of jengkol (Archidendron pauciflorum) fruit peel ethanolic extract to heart histologic of rat induced by streptozotocin. Biofarmasi J Nat Prod Biochem 16: 59-63. Indonesia is ranked 7th out of 10 countries with the highest diabetic patients in the world. Diabetes mellitus is a disease that can cause heart disorders and adults who suffer from DM are four times more likely to develop heart disease. Jengkol fruit peel has been used traditionally as a drug for diabetes mellitus. The aim of this research was to know the effect of fruit peel ethanolic extract of jengkol (Archidendron pauciflorum) (JFPEE) on rat (Rattus norvegicus) heart histological structure and to obtain effective dose from JFPEE. This research used experimental method in laboratory with Completely Random Design (CRD) using 6 treatments and 4 replications. Treatment was given for 14 consecutive days consisting of negative control, positive control, comparison (glibenclamide dose 10 mg/kg BW), P1, P2, and P3 (JFPEE dose 385, 770, and 1.540 mg/kg BW). Diabetic induction was performed with streptozotocin dose 65 mg/kg BW in female wistar rat except for negative control group. The parameters that observed were number of necrosis and cell damage score, including fat degeneration, hydropic degeneration, and inflammatory cell. The obtained data were analyzed by ANOVA-Tukey's test with 95% confidence level using SPSS version 21 for Windows. The result of histological structure showed that number of necrosis and cell damage score in group of rats treated with JFPEE dose 385 mg/kg BW (174.25±6.34; 1.25±0.50) were not significantly different from the negative control rats (172.00±7.62; 1.00±0.00). The effective dose of JFPEE that can repair the damage of heart cell’s rat induced by streptozotocin was 385 mg/kg BW.

CYP2C9*3 gene variant contributes independently to glycaemic control in patients with type 2 diabetes treated with glibenclamide.

Glibenclamide is a prescribed glucose-lowering medication for diabetes, but there are interindividual variations in the therapeutic response. In this cross-sectional study, the aim was to explore the association of genetic variants in CYP2C9, ABCC8, KCNJ11 and TCF7L2 with good glycaemic control in Mexican type 2 diabetes (T2D) treated with glibenclamide. Patients with T2D receiving treatment with glibenclamide or glibenclamide plus metformin were included. Patients with A1C≤7% were considered to have good glycaemic control, whereas patients with A1C≥8% were considered having poor glycaemic control. Genotyping was performed by real-time PCR using TaqMan probes for the genetic variants. Association was performed by calculating OR with 95% confidence intervals (95% CI). For the multivariate analysis, a multiple logistic regression was performed including the confounding variables age, exercised, BMI, glibenclamide dose, time with T2D and concomitant metformin. Four hundred and four patients were included in the study, median age of the participants was 50years (IQR 11.0), the median time with disease was 6years (IQR 8.0), 118 (29.2%) were men, and 243 (60.1%) received glibenclamide in combination with metformin. CYP2C9*3 variant was associated with good glycaemic control (OR=2.747 [95% CI, 1.194-6.324]), whereas the variants, CYP2C9*2, TCF7L2 rs7903146 and rs12255372, ABCC8 rs757110 and KCNJ11 rs5219, were not. In the multivariate analysis, the CYP2C9*3 variant maintained its association (OR=2.779 [95% CI, 1.142-6.763]). The findings suggest that CYP2C9*3 genetic variant independently contributes to good glycaemic control of patients with type 2 diabetes treated with glibenclamide.

Galangin, a dietary flavonoid, ameliorates hyperglycaemia and lipid abnormalities in rats with streptozotocin-induced hyperglycaemia

Context: Galangin, a natural flavonoid, is found in honey and Alpinia officinarum Hance (Zingiberaceae). Galangin has antiviral, antimicrobial, antidiabetic and anticancer properties, without side effects. The effects of galangin on hyperglycaemia and lipid abnormalities are not known.Objective: To elucidate the effectiveness of galangin on hyperglycaemia-associated complications and lipid changes in rats with streptozotocin (STZ)-induced hyperglycaemia.Materials and methods: Diabetes was induced in adult Wistar rats by administering 40 mg/kg of STZ. In our previous study, galangin had no toxicity at concentrations up to 320 mg/kg. Therefore three doses of galangin (4, 8 or 16 mg/kg BW) or glibenclamide (600 µg/kg BW) were administered daily to diabetic rats orally for 45 days.Results: Diabetic rats showed a significant (p < 0.05) increased levels of plasma glucose (281.10 mg/dL) and decreased levels of insulin (6.01 μU/mL). Additionally, diabetic rats showed a significant (p < 0.05) increased levels of plasma lipid profiles such as total cholesterol (149.05 mg/dL), triglycerides (143.28 mg/dL), free fatty acids (139.37 mg/dL), phospholipids (127.53 mg/dL), plasma low-density lipoprotein-cholesterol (98.72 mg/dL), plasma very low-density lipoprotein-cholesterol (28.65 mg/dL), and significant (p < 0.05) decreased in plasma high-density lipoprotein-cholesterol (21.68 mg/dL). When galangin was administered to the hyperglycaemic rats, plasma glucose and insulin levels and lipid profiles reverted to levels similar to those in healthy control rats.Discussion and conclusions: Administration of galangin reduced hyperlipidaemia related to the risk of diabetic complications and could be beneficial for diabetic hyperlipidaemic patients. Further work detailing its mechanism-of-action for improving hyperglycaemic-associated lipid abnormalities is needed.

Evaluation of Antidiabetic Activity of Aqueous Extract of Leaves from &amp;lt;i&amp;gt;Phragmanthera capitata&amp;lt;/i&amp;gt; (Sprengel) S. Balle (Laurenthaceae) in &amp;lt;i&amp;gt;Wistar&amp;lt;/i&amp;gt; Albino Rats

Diabetes mellitus is a public health problem affecting about 8.4% of people in the world and knows an alarming progression in sub-Saharan Africa and in Cameroon precisely. The current therapeutic strategies have prohibitive prices, are unavailable and have harmful side-effects. So, this work aimed at contributing to the valorization of medicinal flora and `knowledge of traditional healers in Foumban, West-Cameroon, in the treatment of diabetes. An ethnopharmacological survey was conducted by consulting traditional healers of the District of Foumban. At the end of this investigation, Phragmanthera capitata, which was found to be the most active plant following preliminary tests, was selected for antidiabetic studies on three groups of rats: normal glycaemia, temporary hyperglycemia and diabetic. The first two groups were treated per os, with aqueous extract of leaves from P. capitata, with the doses of D2 (4 mL/kg) obtained from the traditional healers, D1 (half of D2), D3 (double of D2) and by glibenclamide (2.5 mg/kg). The rats of the last group were treated twice per day, with the same doses of extract and glibenclamide for 13 days and were sacrificed on the 14th day. Their blood was collected by cardiac puncture for the determination of biochemical and hematological parameters. Phytochemical screening was performed using standard methods. The administration of aqueous extract of P. capitata led to a hypoglycaemia effect in normal rats, a reduction of glycaemia in the temporary hyperglycaemia and diabetic rats. In addition, an improvement of lipid assessment, renal and hepatic parameters related to the installation of diabetes, as well as an immune-modulator effect of the extract were noted in diabetic rats treated for 13 days. Phytochemical screening indicated that the extract contains saponins, tannins, flavonoids, steroids and terpens. This work along with findings justifies the traditional use of this plant in the treatment of diabetes mellitus.

Population pharmacokinetics of carvedilol enantiomers and their metabolites in healthy subjects and type-2 diabetes patients

Carvedilol, a drug available as a racemic mixture, is metabolised into hydroxyphenylcarvedilol (OHC) by CYP2D6 and O-desmethylcarvedilol (DMC) by CYP2C9 followed by conjugation to glucuronides. In contrast to other β-adrenergic receptor antagonists, carvedilol does not induce insulin resistance or worsen glycaemic control in diabetic hypertensive patients. This study aims to investigate the implications of type 2 diabetes (T2DM) on the pharmacokinetics of carvedilol enantiomers using an integrated population pharmacokinetic modelling approach. In total, 14 T2DM patients with good glycaemic control receiving standard doses of metformin and glibenclamide were evaluated along with a control group of 13 healthy subjects. Serial blood samples were collected up to 24h after administration of a single 25mg dose of racemic carvedilol. A multicompartmental population pharmacokinetic model describing the enantioselective disposition of the parent compound, OHC and DMC was developed in NONMEM v7.2. Even though data are limited, it appears that despite inhibition of CYP2C9 due to long-term glibenclamide administration to T2DM patients, overall no differences are observed in the total clearance of carvedilol when compared to healthy subjects (43.1 vs. 45.9L/h for (S)-(−)-carvedilol and 29.0 vs. 33.1L/h for (R)-(+)-carvedilol). These results provide evidence of a compensatory mechanism for the inhibition of CYP2C9, with higher contribution of CYP2D6 activity to the elimination of carvedilol. Consequently, no dose adjustment is recommended for carvedilol in T2DM patients receiving glibenclamide and metformin.

Factors of primary and secondary sulfonylurea failure in type 2 diabetic subjects.

The aim of the present study was to investigate the value of clinical characteristics in predicting sulfonylurea (SU) treatment responses. All 747 subjects in the present study were from the Xiaoke Pill Clinical Trial evaluating the safety and efficacy of SU. Subjects had the same initial dose of glibenclamide and drug doses were adjusted every 4 weeks during the 48-week follow-up period. Primary SU failure was defined as a <10% reduction in fasting plasma glucose (FPG) at the end of Week 4 from randomization, whereas secondary SU failure was defined as a consecutive confirmed level of FPG >7 mmol/L. Kaplan-Meier survival analysis revealed that lower baseline basal disposition index (DI b ) and higher FPG predict secondary SU failure. Inversely, higher baseline DI b and lower FPG predict primary SU failure. Primary SU failure can predict secondary SU failure. The combination of lower baseline DI b with primary SU failure is a better predictor of secondary SU failure than lower baseline DI b or primary SU failure alone. Patients with good glycemic control and higher β-cell reserve at entry are more likely to experience primary SU failure but are less likely to experience secondary SU failure. By combining baseline DI b with initial response at the first month of treatment, we can get quick information about the long-term efficacy of SU treatment.

The Effect of Long Term use of Glibenclamide on Serum and Urinary Sodium and Potassium Level in Type 2 DM Patients

Long-term use of sulfonylureas including chlorpropamide, is known to potentiate the antidiuretic action of arginine vasopressin (AVP), predisposing to hyponatremia.The present study was designed to evaluate the effect of long term use of glibenclamide on serum and urinary levels of sodium and potassium in Type 2 DM patients in Iraqi DM centers. Ninety eight patients with Type 2 DM who were maintained on different doses of glibenclamide for at least 1 year, attending the centre for Diabetes and Endocrinology in Al-Rusafa, Baghdad, were enrolled in the study, in addition to 15 normal healthy subjects. Patients were allocated into three groups according to the dose of glibenclamide that they received. Blood and urine samples were obtained for evaluation of sodium and potassium levels in these samples by flamephotometry. The results indicated that glibenclamide use resulted in significant elevation in serum levels of sodium and potassium compared to controls, while urinary excretion of these cations was not significantly changed. Stratification of patients according to the dose of glibenclamide revealed that this effect on sodium and potassium was not dose dependent. In conclusion, long term use of glibenclamide impairs normal values of Sodium and potassium independent of the administered dose. &#x0D; Key words: Glibenclamide, sodium, potassium.