Glibenclamide

One of the most common metabolic diseases during pregnancy period is gestational diabetes mellitus (GDM). It is associated with several perinatal complications, especially in those who have risk factors such as obesity, polycystic ovary syndrome, and a family history of type 2 diabetes mellitus (DM). Some research has shown that physical exercise and medical nutrition treatment can give beneficial effects to control glycemic and body weight for GDM affected women. Furthermore, pharmacological agents such as insulin and a specific oral antidiabetic can be prescribed safely during pregnancy to decrease maternal glucose blood. Therapy of GDM is needed to control blood for the wellness of the patient during and after the pregnancy. The main treatment therapy for GDM is lifestyle modification, which includes medical nutritional therapy and daily physical exercise. In the special case of disorder glucose level, drug therapy will be given to the patient. Insulin is the chosen drug because ...

Introduction: Therapeutic equivalence of medications is carried out through in vitro and in vivo studies called bioequivalence studies. Objective: To determine the in vitro therapeutic equivalence of the 5 mg glibenclamide multi-source tablets respecting the reference medicine. Materials and methods: Both, the multi-source drug 5 mg glibenclamide and the reference 5 mg Glidiabet are made in Peru, and were acquired in a drugstore of Ica city (Peru). Reagents and an analytical grade standard were used. The Ultraviolet absorption method at 300 nm was used on each of the three dissolution media. Results: Neither the multi-source drug T nor the reference R dissolved by 85% at pH 1.2 and at pH 4.5, during 15 or 30 minutes. However, at pH 6.8 dissolution occurs. These results correspond to Food and Drug Administration and United States Pharmacopoeia criteria. The similarity factor value was within the acceptance range (50-100) for the three tested pHs. Dissolution efficiency was 68.66% (pH...

Context: Sustained release drug delivery systems are more preferred than the conventional drug delivery systems due to its enhanced bioavailability and patient compliance. Earlier studies reported on glibenclamide (GBCM) were not clear and hence, the step has been taken to explore the sustained release drug delivery system of GBCM.

Aims: To evaluate the sustained release microspheres obtained of GBCM.

Methods: Microspheres were prepared by ionic gelation method using the polymers like Eudragit RS 100 and xanthan gum. Polymers can sustain the drug release from microspheres. The prepared microspheres were subjected to micromeritic studies like Carr’s index, Hausner’s ratio and angle of repose.

Results: Micromeritic studies confirmed that the microspheres possessing acceptable flow properties. It was observed from the in vitro release studies, formulations F8 and F9 showed sustained drug release for desired time of 12 h and when compared to F9, formulation F8 showed maximum drug release for 12 h.

Conclusions: Results confirmed the formulation F8 consist of the polymers such as Eudragit RS 100 about 150 mg and xanthan gum about 100 mg showed desired sustained release of 12 h with 96.07% and kinetic studies confirmed that the release from microspheres followed non-Fickian diffusion mechanism. Due to its sustained release property, it could enhance the bioavailability of drug thereby improves the patient compliance and expect better treatment than conventional dosage forms.

Syzygium cumini is commonly known as insulin plant in India. Consumption of leaves of this plant are believed to lower blood glucose level in healthy normal and diabetic individuals. The present study was planned to evaluate the effect of the leaves of syzygium cumini leaves on dexamethasone induced hyperglycemic rats. MaleWistar rats (n=6) were treated with 10mg/kg of dexamethasone subcutaneously for 20 days from 11 th day to 20 days. Different groups received 100mg/kg plant extract in distill water and glibenclamide 500µg/kg per orally on plasma blood glucose level, serum total cholesterol, triglyceride level, HDL, LDL and Serum VLDL were observed. Dexamethasone caused an increase blood glucose level, serum total cholesterol, serum triglyceride level, Serum HDL ,Serum LDL and Serum VLD and compare with normal control[ **P<0.01]. In the dexamethasone model 100mg/kg p.o. of Ethanolic extract of syzygium cumini leaf showed significant decrease in blood glucose level, serum total cholesterol , serum triglyceride level, Serum HDL ,Serum LDL and Serum VLDL when compared to dexamethasone control[l.**P<0.01]. The study results concluded Syzygium cumini proved to be effective in treatment of Type-II Diabetes mellitus owing to its ability to decrease insulin resistance.

More than 100 million people worldwide are affected by a complex and heterogeneous disorder of Type 2 diabetes causing serious socio-ecologic problems. The different extracts of the bark of Cuscuta reflexa (Cuscutaceae – Dodder family) were tested for anti-diabetic activity, by alloxan induced diabetic rats and glucose tolerance test in normal rats. The blood glucose level of normal and experimental animals after oral administration of glucose (2 g/kg) the extract as well as standard drug treated animals showed more significant decrease in peak blood glucose level after 1 h. After 2 h, the extract treated animals tended to bring the values near normal. The extract produced significant decrease in the blood glucose level when compared with the controls in alloxan induced hyperglycemic rats in the single dose experiment at the tested dose level and are comparable with the standard drug glibenclamide. The ethanolic extract reversed the weight loss of the diabetic rats and they returned to near normal. This study gave a clear view that the ethanolic extract prevented significant elevation of glycosylated hemoglobin in vitro, with IC50 value being 11.25 μg/ml that is comparable with the reference drug α- tocopherol, since the non-enzymatic glycosylation of hemoglobin is an oxidative reaction.
Keywords: Cuscuta reflexa, hypoglycemic activity, alloxan, glibenclamide, α- tocopherol.

Abstract: The suspensions of sulfonylurea glyburide (glibenclamide) are compounded extemporaneously for patients suffering from transitional and Permanent Neonatal Diabetes mellitus (PND). The purpose of this study is to compare the stability of three different galenic liquid formulations compounded from tablet containing glibenclamide. The samples were stored at refrigerated (2-8°C) and room temperature and analyzed at different times. All formulations analysed are stable for at least 90 days, but only two guarantee the administration responding to prescription, especially when it comes to giving dosages very small.

Talinum triangulare is used by some traditional healers to manage preterm labour and prevent preterm birth. The effect of T. triangulare on uterine contractility is so far unknown. This study was therefore aimed at: the investigation of the pharmacological and physiological effect of T. triangulare leaf extract (MTT) on the isolated mouse uterus; investigation of possible mechanisms of activity and identification of significant metabolites present in the leaves. Longitudinal uterine segments from non-pregnant mice were isolated and mounted in a continuously aerated organ bath containing physiological salt solution and maintained at 37°C. The effect of MTT (0.0007 -7.777 µg/ml) on spontaneous contractions, 11.82 nM oxytocin, and 40 mM KCl was investigated. Additionally, MTT (3.43 mg/ml) in the presence of 95.34 nM amiodarone, 5.06 nM glibenclamide and 11.57 nM propranolol was investigated. High resolution mass spectrometric (HRMS) analysis was performed on MTT. MTT exerted a biphasic effect on spontaneous uterine contractility, with low concentrations inhibiting and high concentrations stimulating contraction. MTT also increased oxytocin and KCl-induced contraction. The effect on oxytocin was reduced in the presence of amiodarone but not glibenclamide or propranolol. HRMS identified high levels of oestrogenic compounds which may play a role in the activity of the plant on female reproductive health

Abstract
BACKGROUND: Severe hypoglycemia is a frequent cause of hospi- talization in Mexico.
OBJECTIVE: To identify the clinical and laboratory characteristics as- sociated to severe hypoglycemia in consecutive patients with severe hypoglycemia and normal creatinine serumvalues.
PATIENTS AND METHOD: A prospective study was done from August 11, 2011 to May 31, 2013, including patients with severe hypoglyce- miaandnormal creatinine serumvalues.Age, sex, timeof evolutionof diabetesmellitus2,antidiabetictreatment,comorbiditiesand24-hour urine creatinine clearance wererecorded.
RESULTS: From 234 patients with severe hypoglycemia admitted, 21 (9%)hadnormalcreatinine:13women(62%)and8(38%)men,with
amean age of 64.76 years (range: 42-84); 13 (62%)were older than
60 years; 15 (71%) hadmore than 5 yearswithDM2(mean evolution
of 9.2 years); 15 received glibenclamide (71%),4 in combinationwith insulin(19%)and8withmetformin(38%).Tworeceivedrosiglitazone plusinsulin.Fourpatientshadnotcomorbidities(19%);16hadarterial hypertension (71%) and 3, neoplasms (adenocarcinoma, gastric carci- nomaandesophagealcarcinoma).Elevenpatients(52%)wereadmitted with syncope, 5 with disorientation (24%), 4 with conduct disorders (19%)andonewithdyslalia(5%);15of21patients(71%)hadadvanced degreesofrenalimpairment,despitenormalcreatinineserumvalues.
CONCLUSIONS: It is important to perform creatinine clearance at all levels of care, the only guide for safe treatments according to kidney function. Glibenclamide should be cautiously prescribed in older adults with a history of more than 10 years of diabetesmellitus 2 and should be avoided in those with documented chronic renal failure.
KEYWORDS: hypoglycemia; diabetes mellitus 2; oral antidiabetic drugs; chronic kidney failure

A large number of oral antidiabetic agents are available today. This article provides a short review of the pharmacology and some clinical aspects of various oral antidiabetic drugs. It focuses mainly on the newest developing drugs (therapy of the near future) and on the most commonly used older groups for the common approach of everyday practice (sulphonylureas). The primary goal of this review is to compare the electrophysiological effects of glibenclamide in isolated normal and streptozotocin induced diabetic rats and alloxan induced rabbits ventricular preparations, while on the other hand to differentiate the hypoglycaemic sulphonylureas (0.1-1000 mmol/kg) according to their cardiovascular activity in healthy and diabetic animals. In vitro (1-100 mmol/l) as well as chronically treated (5 mg/kg for 10 weeks) glibenclamide prolonged the action potential duration in normal but failed to affect it in diabetic ventricular preparations. Our results suggest that the sensitivity to glibenclamide of KATP channels in diabetic ventricular fibers is drastically decreased. The effects of different sulphonylureas (tolbutamide, glibenclamide, gliclazide, glimepiride) on ventricular ectopic beats as well as the duration of ventricular fibrillation induced by 10 min ischemia/50 min reperfusion in healthy and diabetic rats were compared. Tolbutamide and gliclazide dose-dependently enhanced both parameters both in healthy and diabetic groups. Glibenclamide in healthy rats increased, while in diabetic rats it decreased the arrhythmogenicity. Glimepiride depressed the arrhythmogenicity in both healthy and diabetic animals. Glimepiride proved to dose-dependently enhance the myocardial tissue flow in dog in contrast to glibenclamide. These results confirm that glimepiride has less cardiovascular actions than other sulphonylureas. From the newest oral antidiabetics this review tries to emphasize the most important basic pharmacological properties, mechanism of action, therapeutic use.

Context: Diabetes mellitus (DM) is a metabolic hyperglycemia disease caused by abnormalities in insulin secretion and the highest increase in diabetes sufferers that occurred in Southeast Asian countries, including Indonesia. The sikkam leaf (Bischofia javanica) ethanolic extract contains many secondary metabolites, and some of them are quercetin and gallic acid, which have the potential to be used as antidiabetic.

Aims: To analyze apoptosis via cytochrome c in aortic tissue of DM after giving B. javanica leaves.

Methods: The treatment group consisted of G0: Negative control, G1: Positive control (alloxan induction + standard feed), G2: Alloxan induction + 300 mg/kg BW of B. javanica leaves ethanol extract, G3: Alloxan induction + 600 mg/kg BW of B. javanica leaves ethanol extract, G4: Induction of alloxan + ethanol extract of B. javanica leaves 900 mg/kg BW and G5: Induction of alloxan + glibenclamide 0.5 mg/kg BW. Fourteen days later, the rats were dissected, and the aortic tissue was analyzed for apoptosis by tunnel assay and cytochrome c by immunohistochemistry.

Results: There was a statistically significant difference (p<0.01) in the apoptotic value and cytochrome c. Increasing the dose of B. javanica leaves, the cytochrome c expression, and apoptotic value decreases in the aorta of DM rats. The cell shape returned to normal after being given B. javanica ethanol extract 900 mg/kg BW than glibenclamide.

Conclusions: Bischofia javanica ethanolic extract reduced apoptosis via cytochrome c in aortic histology, and this plant can be developed into a diabetic drug candidate.

Background: The leaves of Thaumatococcus danielli (Benth.) have been traditionally used in folk medicine to treat malaria in Nigeria. However, there is no report on whether these leaves contain Nephroprotective activity. Thus, the ethanol leaf extract was investigated for Nephronprotective activity in Streptozotocin induced diabetic rats.

Methods: First, the LD50 of the leaf was determined using standard procedure. Rats were assigned to 5 groups (A-E) of five rats. Except for the control group, each group was made
diabetic using Streptozotocin (65 mg/kg/b.wt. i p). The treated groups received 0.5 ml of glibenclamide (25 mg/kg/b.wt, o.p), 250 and 500 mg/kg/b.wt, o.p of Thaumatococcus danielli respectively. After 14 days of treatment, animals were sacrificed under light anaesthesia. Data expressed as Means ± S.D (n=5) and was analyzed using one-way ANOVA followed by Dunnet’s test. Values were considered significant at p<0.05.

Results: The plant showed a LD50 greater than 5000 mg/kg/b.wt in albino rats observed for 72 hours. A significant (p<0.05) decrease in serum Na+, Cl-, HCO-
3, total protein, and an insignificant increase in K+, urea and creatinine level were observed in the diabetic group when
compared with the normal group. Oral administration of plant extract and glibenclamide significantly (p<0.05) restored the electrolytes to near normal. Histological alterations such as glomerulonephritis and tubules infiltration by inflammatory cells observed in diabetic control
were also reversed.

Conclusion: This study suggests renal protective ability of the plant against impairment due to hyperglycemia.

Keywords: Streptozotocin, Thaumatococcus danielli, Nephroprotective, Glibenclamide, serum electrolytes.

Introduction: Studies suggest that ATP-sensitive potassium (KATP) channels are a potential
pharmacotherapeutic target for neuroprotection in neurodegenerative diseases. The current
study aimed at evaluating the effect of pretreatment with glibenclamide (Glib) and B vitamins
supplement on the severity of behavioral symptoms in 6-hydroxydopamine (OHDA)-induced
Parkinsonism. Also malondialdehyde (MDA) concentration was measured in the blood and brain
suspensions to find probable neuroprotective mechanism of Glib.
Methods: The 6-OHDA was injected into striatum of rats by stereotaxic surgery. Treatment
with Glib and B vitamins was started before the surgery and continued up to 3 weeks after that.
Development and severity of Parkinsonism were evaluated by conventional behavioral tests.
MDA values were measured spectrophotometrically using thiobarbituric acid and MDA standard
curve.
Results: Pretreatments with Glib, at both doses of 1 and 5 mg/kg or B vitamins significantly
ameliorated severity of the behavioral symptoms. Pretreatment with a combination of Glib and B
vitamins was more effective than pretreatment with Glib or B vitamins alone. Also, pretreatment
with B vitamins, Glib, or a combination of them reduced MDA concentration in the brain
suspensions. Decrease in MDA concentration in the group of rats that received a combination of B
vitamins and Glib was more prominent than that of the Glib groups.
Conclusion: As severity of the behavioral symptoms in the 6-OHDA-induced Parkinsonism
reflects the degree of the lesion in Substantia Nigra (SN) dopaminergic neurons, it is suggested
that Glib pretreatment has neuroprotective effect against 6-OHDA-induced neurotoxicity. The
current study data also showed that this effect may be mediated by antioxidant effect of Glib.

Objectives: The present study was undertaken to determine the interaction of glibenclamide with methanolic extract of bark of Ficus glomerata Roxb. (FBME).
Methods: The interaction was evaluated in normal and alloxan-induced diabetic rats using the parameters such as glucose tolerance test, acute and subacute levels of antidiabetic study and body weight estimations at various intervals. Glibenclamide was administered orally at two different doses of 300 µg/kg (low dose) and 600 µg/kg (high dose) and FBME was co-administered at the dose of 200 mg/kg. Individual treatments of above drugs were also carried out.
Results: The combination therapy of glibenclamide and FBME showed significant (P<0.01) hypoglycemic effect compared to their individual treatments in the parameters studied and it also showed more percentage increase in body weight than the individual treatments.
Conclusion: The present herb-drug interaction was found to be beneficial as it was observed that FBME showed synergistic effect with glibenclamide. This could provide an opportunity to reduce the dose of glibenclamide to achieve an enhanced therapeutic effect with minimal side effects.

Purpose: To examine body mass index (BMI), occupation, sex, age, and duration of therapy as contributory factors in treatment failure in type 2 diabetic patients taking metformin and glibenclamide in a tertiary hospital in Northwestern Nigeria. Method: A retrospective case control study was employed where variables (age, sex, body mass index, tribe, duration of therapy, glycaemic profile and occupation) for a total of 520 type 2 diabetic patients that took metformin and glibenclamide for a minimum of 1 year were examined. Patients were classified into two groups based on progression to triple oral therapy or a switch from metformin and glibenclamide therapy. Results: Of the 520 patients analysed, 276 failed treatment. Over 90 % of the patients were&gt; 40 years while 61 % had been on treatment for&gt; 4 years. The subjects ’ mean age was 53.22 ± 9.03 years. The mean population body mass index (BMI) was 27 kg/m2. Housewives comprised more than half of the population (55.5 %). The mea...

Diabetic patients, habitually, use plants and plant products those assumed to have an anti-hyperglycemic desire often combined with the oral anti-diabetic medication given. The subsequent interaction between the ingested plant and the medication taken may affect the pharmacology and toxicology profile of which either component 298 leads to number of categorizing effects. This study designed to investigate the anti-diabetic properties of the mixture of Swietenia macrophylla seeds and endocarps aqueous extract in STZ-induced diabetic rats, and also to assess the possible plant-medication interaction with glibenclamide. Twenty four male rats (Sprague Dawley) made diabetic, they were orally force-fed with glibenclamide, mixture of seeds and endocarps aqueous extract and combination of full strength extract with half of the previous glibenclamide dosage, daily for three weeks. Body weight and FBG levels were determined at treatment intervals of 0, 7, 14 and 21 days. Both glibenclamide and plant extract showed hypoglycemic effect. Highest significance found in the group with combined treatment of plant extract plus glibenclamide. We concluded that the use of the aqueous extract of Swietenia macrophylla King seeds and endocarps in combination with glibenclamide can exhibit potent additive anti-diabetic effect in rats.