glucotrol xl generic
On the fasting-exercise day, fasting glucose concentrations were lower (153 vs. 241 mg/dl, P < 0.01) and insulin and C-peptide concentrations higher in the extended-release glipizide group. The decrement of glucose from the fasting baseline was modest and equivalent in the two groups: 17 vs. 21 mg/dl at the end of exercise and 28 vs. 27 mg/dl after 2 h of recovery. No subject had hypoglycemic symptoms.
Spray dried dispersions (SDDs) of glipizide, a BCS Class II model drug, were prepared using various grades of hydroxypropyl methylcellulose acetate succinate (HPMCAS) and copovidone S-630 as carriers. The SDDs appeared as a single amorphous phase with up to 60% drug loading level as revealed by X-ray powder diffraction (XRPD), modulated differential scanning calorimetry (mDSC) and scanning electron microscopy (SEM). Supersaturated micro-dissolution testing of various SDDs in fasted state simulated intestinal fluid showed prolonged supersaturation state (up to 180min) with solubility increases of 5.2-13.9 fold relative to crystalline drug under similar conditions. Solubility and stability characteristics of the most desirable SDDs in terms of relative dissolution AUCs (AUC(SDD)/AUC(crystalline)) and supersaturated concentration ratios (C180/Cmax) were determined. Results show that HPMCAS-based SDDs achieve a higher degree of supersaturation compared to Copovidone S-630 and that SDDs comprising HPMCAS-M and HPMCAS-H maintained stable supersaturated concentration. Dissolution data showed that SDD-loaded CR tablets provide stable supersaturated concentration within the hydrated matrix with increased rate and extent of drug dissolution over 24h. Co-existence of HPMCAS and HPMC within the hydrating matrix showed strong suppression of drug crystallization and allowed achievement of zero-order and slow-first order release kinetics.
glucotrol name brand
It is feasible to use (99m)Tc-DTPA-GLP to assess pancreas beta cell receptor recognition. (99m)Tc-DTPA-GLP may be helpful in evaluating patients with diabetes, pancreatitis and pancreatic tumors.
In vitro iontophoretic delivery of glipizide across the pigskin was investigated. The experiment was carried out at three different donor drug concentrations using cathodal iontophoresis (current density 0.5 mA cm(-2)) with corresponding passive controls. At all concentration levels, iontophoresis showed enhanced permeation rate compared to passive controls (P<0.01). For passive permeation, the steady-state flux significantly increased with the increase in donor drug concentration (P<0.01). Passive process followed zero-order profile while the profile was nonlinear in iontophoresis. Competition by chloride ions released in the cathode compartment could be the reason. Flux enhancement was highest at the lowest drug load and lowest at the highest drug load. The target flux of glipizide was calculated to be 0. 4147 micromol h(-1). As the highest flux obtained was 0.2727 micromol cm(-2) h(-1), it can be said that glipizide is a promising candidate for iontophoretic delivery.
glucotrol pill identifier
In this study we examined the acute in vivo effect and short- and long-term in vitro effects of samples from native and commercial Ilex paraguariensis on glucose homeostasis. Also, the potential effect of I. paraguariensis on serum insulin secretion was investigated. The chemical identification and quantification of methyl xanthines and polyphenols in CH₂Cl₂, EtOAc and n-BuOH fractions of native I. paraguariensis as well as infusions of green and roasted I. paraguariensis from a commercial source was verified by high-performance liquid chromatography. The results for the serum glucose-lowering indicated that both fractions and both infusions were able to improve significantly the oral glucose tolerance curve. Additionally, both the EtOAc and n-BuOH fractions induced-insulin secretion, but EtOAc induced an early (at 15 min) and late (at 60 min) biphasic peak of insulin secretion similar to glipizide stimulatory effect. Both fractions increased liver glycogen content compared with fasted normal rats. Also, EtOAc and n-BuOH fractions inhibited in vitro disaccharidases activities after an acute treatment. The maximum inhibitory effect of the EtOAc and n-BuOH fractions on maltase activity (at 5 min) was around 35%. The evident reduction of protein glycation by glucose or fructose with EtOAc and n-BuOH fractions increased from 7 to 28 days of in vitro incubation. Inhibition of bovine serum albumin glycation by glucose and fructose, by around 50% and 90%, respectively, was observed. Additionally, the green and roasted mate infusions reduced the formation of AGEs in a characteristic long-term effect. In conclusion, this study shows that I. paraguariensis has an anti-hyperglycemic potential role able to improve the diabetic status and is probably a source of multiple hypoglycemic compounds.
glucotrol brand name
The work describes a comprehensive evaluation of five blood microsampling techniques (tail clip, tail vein with needle hub, submandibular, retro-orbital, and saphenous bleeding) in CD-1 mice. The feasibility of blood sampling was evaluated based on animal observations, ease of bleeding, and ability to collect serial samples. Methotrexate, gemfibrozil and glipizide were used as test compounds and were dosed either orally or intravenously, followed by DBS collection and LC-MS/MS analysis to compare PK with various bleeding methods.
glucotrol renal dosing
This review aimed to address effects of sustained-release versus immediate-release glipizide on glucose control, insulin secretion, and compliance. We searched Medline, EMBASE, the Cochrane Library, and Chinese Biomedical database from inceptions to May 31, 2011, screened reference lists of relevant studies, and contacted pharmaceutical companies. Randomized trials and cohort studies were included. We pooled data using a random-effect model. Nineteen trials involving a total of 1440 patients and 2 retrospective cohort studies with a total of 13452 patients were included. Trials were of low quality. No trials reported patient important outcomes. The reduction of fasting plasma glucose from the baseline appeared larger for sustained-release than for immediate-release glipizide (mean difference -0.26 mmol/L, 95% CI -0.52 to -0.01). The reduction was not significantly different between the two drugs for HbA1c (-0.03%, -0.20% to 0.14%) or 2-hour postprandial plasma glucose (-0.21 mmol/L, -0.96 to 0.55). Sustained-release glipizide appeared to reduce insulin secretion from the baseline, whereas the immediate-release formulation increased the secretion (fasting insulin: -1.04 vs. 0.88 μIU/ml; 2-hour postprandial insulin: -2.94 vs. 0.24 μIU/ml). Patients administering sustained-release glipizide had less hypoglycemia (Peto odds ratio 0.21, 95% CI 0.08 to 0.52) and lower missed dosing (Peto odds ratio 11. 42, 95% CI 6.47 to 20.18). The cohort studies showed patient compliance results consistent with those of the trials. Sustained-release glipizide appears to achieve similar glucose control with decreased insulin secretion, fewer hypoglycemic episodes, and higher patient compliance than immediate-release glipizide. However, these findings are inconclusive due to inadequate study quality, short follow up, and unavailability of patient important outcomes.
glucotrol xl dosage
K+ channels play a key role in regulation of membrane potential and cell excitability. Several different types of K+ channels have been identified and the presence, characteristics and functions of these channels vary among different tissues. The 3 most important K+ channels in smooth muscle are the KATP (activated by a fall in intracellular ATP and a rise in nucleotide diphosphates and blocked by glibenclamide), BKCa (activated by a rise in intracellular Ca2+) and Kv (activated by depolarization). Cromakalim, pinacidil and nicorandil are members of a rapidly increasing group of novel drugs which open K+ channels. Opening of such channels leads to K+ efflux, membrane hyperpolarization, reduced excitability and smooth muscle relaxation. The purpose of the studies included in this thesis was to investigate this novel drug principle of K+ channel modulation on smooth muscle contractility of isolated airways and arteries and on neuroeffector transmission in airways. Smooth muscle contractility was measured in airway and vascular ring preparations suspended in isometric myographs. Neurotransmitter release was elicited by transmural electrical field stimulation. The major findings were: 1) Membrane depolarization by high extracellular K+ concentrations induced contraction of airway smooth muscle that was easily relaxed by Ca2+ antagonists and abolished in a Ca2+ free medium indicating that K+ contraction is triggered by Ca2+ influx through voltage-operated Ca2+ channels. Indomethacin was required to obtain reproducible responses upon repeated exposure to K+ suggesting that endogenous prostaglandins are released by K+ and interferes with its contractile effect. K+ depolarization was shown to be a valuable pharmacological tool for detection of drugs acting by K+ channel opening. The prototype K+ channel opener cromakalim relaxed contractions induced by 20-30 mM K+ but had no effect against contraction induced by 124 mM K+. This was a unique profile of action not shared by other types of airway and vascular smooth muscle relaxants. As the extracellular K+ concentration is raised the outward directed electrochemical gradient for K+ is reduced and at high K+ concentrations the effect of K+ channel opening is negligible. Although the K+ channel opener pinacidil had a higher relaxant potency against contraction induced by 30 mM K+ than by 124 mM K+, it still relaxed the latter contraction indicating an additional K+ channel independent mechanism of action of the drug. When K+ depolarization is used as a pharmacological tool, it is essential to maintain osmolarity. Addition of KCI directly to the tissue bath solution, which previously was a commonly applied technique, produced confounding and unwanted effects due to hyperosmolarity per se. 2) Pinacidil and cromakalim relaxed guinea-pig trachea either tone was spontaneous or induced by a range of airway spasmogens (histamine, PGF2 alpha, LTC4/LTD4 or carbachol) of relevance as asthma mediators. The relaxant effectiveness of the drugs was reduced when tone was elicited by carbachol. The airway smooth muscle relaxation produced by pinacidil and cromakalim was selectively blocked by the antidiabetic sulfonylureas glibenclamide, glipizide and glibornuride and also by phentolamine. These drugs are blockers of KATP which therefore indicates that this channel is the target for cromakalim and pinacidil in airway smooth muscle. Additional to the antagonistic action against K+ channel openers the sulfonylurea KATP blockers and phentolamine at higher concentrations relaxed airway smooth muscle by yet unknown mechanisms that seemed unrelated to KATP. 3) Cromakalim and pinacidil inhibited nerve-mediated e-NANC contractile responses in guinea-pig bronchi. Such responses are due to release of SP and related tachykinins from sensory nerve endings. These neuropeptides cause bronchoconstriction and airway inflammation and may possibly play an important role in the pathophysiology of asthma.
glucotrol xl dosing
A split calibration curve approach is employed to determine the drug concentration in plasma samples with accuracy and precision over a wide dynamic range of approximately 0.6 to 15,000 ng/ml for dapsone and approximately 1 to 25,000 ng/ml for cyclophosphamide and glipizide. A wide dynamic range of concentrations for these three compounds was used in the current study to construct split calibration curves and was successfully validated for sample analysis in a single run.
glucotrol glipizide dose
We retrospectively examined data from 17,773 type 2 diabetic patients seen from March 2, 1998, to December 13, 2010, in 3 Veterans Administration medical centers. Severity was measured using patients' inpatient and outpatient comorbidities during the last year of visits. Severity-adjusted logistic regression was used to measure the odds ratio for mortality within the study period.
glucotrol drug interactions
In type 2 diabetic patients, cases who developed CAD were compared retrospectively with controls that did not. The 20-year risk of CAD at diagnosis of diabetes, using the UKPDS risk engine, was used to match cases with controls.
glucotrol drug classification
Cryptococcosis is an opportunistic infection caused by Cryptococcus neoformans that typically presents in immunocompromised patients, most commonly in those with human immunodeficiency virus (HIV) infection. It rarely has been described in patients with diabetes mellitus (DM). Defects in the host defense mechanisms due to hyperglycemia predispose diabetic patients to opportunistic infections such as cryptococcosis. We present a rare case of disseminated cryptococcosis in a 48-year-old HIV-negative man with DM.
The aim of this review was to discuss the efficacy and tolerability of noninsulin therapies for type 2 diabetes mellitus (T2DM), with an emphasis on patients aged ≥65 years.
glucotrol and alcohol
Chronic use of extended-release glipizide does not enhance the hypoglycemic effect of fasting plus mild exercise for people with NIDDM. Routine lifestyle treatments for NIDDM may be continued during ongoing use of this agent.
Long-term studies on the comparative efficacy and relative potency of glipizide and glyburide are sparse and controversial.
We have previously shown that tight metabolic control by insulin therapy reduced thromboxane-dependent platelet activation in non-insulin-dependent diabetes mellitus (NIDDM) patients. The present study was undertaken to determine whether a similar effect could be obtained without switching diabetics in secondary failure to insulin treatment. For this purpose, we gave strict diet and exercise advise program and adjusted on a weekly basis the oral antidiabetic therapy (glipizide) that 26 patients with NIDDM had been given over the previous months. Basal measurements of urinary 11-dehydro-TXB2 and PAI-1 confirmed previous findings of enhanced levels of these parameters in NIDDM patients with macrovascular disease in comparison to age- and sex-matched controls. After 2-6 weeks, 16 patients achieved tight metabolic control associated with significant reduction of both thromboxane biosynthesis and PAI-1 levels; 10 patients remained in poor control and no significant decrease of both parameters was observed. We conclude that reduction of in-vivo platelet activation and PAI-1 antigen levels after metabolic improvement obtained by frequent reassessment of sulphonylurea therapy together with strict diet and exercise programs may have beneficial effects on the progression of diabetic micro- and macrovascular disease.
The physiology of counterregulatory responses during hypoglycemia in intensively treated type 2 diabetic subjects is largely unknown. Therefore, the specific aims of the study tested the hypothesis that 1) 6 months of intensive therapy to lower A1C <7.0% would blunt autonomic nervous system (ANS) responses to hypoglycemia, and 2) antecedent hypoglycemia will result in counterregulatory failure during subsequent hypoglycemia in patients with suboptimal and good glycemic control.
buy glucotrol online
In this study, carboxymethyl derivative of locust bean gum was prepared, characterized, and its gelling ability with different concentrations (1-5% w/v) of aluminum chloride (AlCl(3)) was utilized for the development of glipizide-loaded beads in a completely aqueous environment. The beads were spherical when observed under a scanning electron microscope. Increase in gelling ion concentration decreased the drug entrapment efficiency from 97.68% to 95.14%. The beads swelled more slowly in pH 1.2 KCl-HCl buffer and exhibited a slower drug release pattern than that observed in pH 7.4 phosphate buffer. Irrespective of the dissolution media, the drug release became slower at higher AlCl(3) concentration. The drug release in alkaline medium was found to be controlled by a combination of diffusion as well as polymer relaxation phenomena. Comparing the release profiles, it was observed that the beads treated with 5% AlCl(3) provided slower drug release up to 10 h in alkaline medium without any sign of disintegration and, thus, this formulation was selected for further studies. Fourier transform infrared (FTIR) spectroscopy indicated the stable nature of the drug in the beads. Differential scanning calorimetry and X-ray diffraction analysis showed that most of the drug remained in amorphous state in the beads. Stability study indicated no statistical significant difference in drug entrapment efficiency of the beads. In vivo activity of the beads was tested and a prolonged hypoglycemic effect was achieved. Hence, carboxymethyl locust bean beads could be a potential carrier for controlled oral delivery of glipizide.
glucotrol maximum dose
More than 8 million Americans are afflicted with non-insulin-dependent diabetes mellitus (NIDDM), a complex disease process characterized by insulin resistance and impaired insulin secretion. Diet and exercise continue to be the cornerstones of treatment. Most patients, however, require the addition of an oral sulfonylurea agent to achieve adequate glucose control. The second-generation sulfonylureas, glyburide and glipizide, are effective at lower doses and may have fewer adverse effects and drug interactions than the older, first-generation agents. For these reasons the second-generation sulfonylureas are preferred. Insulin therapy is required in patients with hyperosmolar state, infection, or other forms of stress, or in those who fail to respond to treatment with oral sulfonylurea. Some patients may benefit from the concurrent administration of insulin and an oral agent. Hypoglycemia is the greatest risk of drug therapy in elderly patients with NIDDM. This is especially true in elderly patients who are exquisitely sensitive to the effects of sulfonylureas and insulin. Treatment should, therefore, be initiated at very low doses and gradually adjusted.
glucotrol 50 mg
Peripheral blood glucose, plasma insulin and C-peptide levels were investigated after giving a standardized breakfast (500 kcal, 60 g carbohydrates) to 10 nonobese Type 2 diabetic patients previously treated by diet alone. Each patient received at random, at 1 week intervals, either 5 mg glipizide (meal + glipizide) or a placebo (meal alone) 30 min before breakfast. Basal values of blood glucose, plasma insulin and C-peptide were similar on both occasions. After meal + glipizide, the blood glucose increase was sharply limited whereas the rise in plasma insulin was steeper and reached twice as high a level. In contrast, the rise in plasma C-peptide was similar in both conditions. Consequently, the areas under the curves (0-300 min) showed a marked reduction in blood glucose after meal + glipizide (2289 +/- 149 versus 3101 +/- 169 mmol X min/1; 2p less than 0.001), associated with a significant increase in plasma insulin (14219 +/- 3261 versus 7591 +/- 1173 microU X min/ml; 2p less than 0.025) but no significant change in plasma C-peptide (342 +/- 45 versus 326 +/- 34 pmol X min/ml; N.S.). The insulin/C-peptide molar ratio was thus significantly increased after meal + glipizide (0.41 +/- 0.06 versus 0.23 +/- 0.04 at the 60th min; 2p less than 0.02). The dissociation between the responses of insulin and C-peptide suggests that a single dose of 5 mg glipizide in Type 2 diabetic subjects may enhance availability of peripheral insulin by extrapancreatic mechanism(s). This phenomenon may result in a higher circulating level of the hormone and therefore represent a further mode of action of sulphonylureas.(ABSTRACT TRUNCATED AT 250 WORDS)
Several oral antidiabetics and diuretics show phototoxic effects in the HaCaT cell line. Inhibiting effects of antioxidants point towards involvement of reactive oxygen species in phototoxic DNA damage, suggesting a link between the phototoxic and photocancerogenic potential of the sulfonamide-derived oral antidiabetic and diuretic drugs. Excessive exposure to UV light may be deleterious for patients treated with oral antidiabetic and diuretic drugs.
The aim of this paper is to present a three-year observation of four children with permanent neonatal diabetes caused by heterozygous activating mutations in both KCNJ11 gene for Kir6.2 and ABCC8 gene for SUR1 subunits (three patients after three years of clinical observation and one patient after two years of clinical observation, respectively). In three cases with Kir6.2 mutation, developmental delay was diagnosed. In all four patients the glucagon test revealed normal c-peptide secretion. During the treatment with sulfonylureas (SU), glycaemia remained within the normal range, HbA1c<7%, in our patients. In all children reduction a of SU doses was required.
glucotrol diabetes medicine
Glucokinase activators (GKAs) are currently being developed as new therapies for type 2 diabetes and have been shown to enhance beta cell survival and proliferation in vitro. Here, we report the effects of chronic GKA treatment on the development of hyperglycaemia and beta cell loss in the male Zucker diabetic fatty (ZDF) rat, a model of type 2 diabetes with severe obesity.
glucotrol max dose
Twenty out-patient and twenty in-patient adult Nigerian type II diabetics and twenty healthy subjects matched for sex, age and weight, were studied at Nnamdi Azikiwe University Teaching Hospital, Nnewi, Nigeria. Mean total cholesterol and fasting blood glucose concentrations were higher in the diabetics. The out-patients had significantly higher total cholesterol and fasting blood glucose values than their in-patient counterparts. The possible cardiovascular risk of the raised cholesterol level in the diabetics was discussed. We recommend that for effective management of diabetic patients, periodic measurement of cholesterol level is necessary. An integrated enlightenment programme to acquaint the out-patients with the health benefits of dietary and drug compliance and occasional hospitalisation for better monitoring would be desirable.
generic glucotrol xl
A retrospective cohort study design of patients with type 2 diabetes treated at 3 Veterans Affairs Medical Centers and 1 Department of Defense Medical Center was utilized. One hundred percent of patients receiving glyburide-metformin tablets were screened for inclusion. Patients with at least 6 months of prior SU+Met combination therapy and a baseline A1C measured within 35 days prior to or 3 days after switch to glyburide-metformin tablets were included. At least one documented follow-up A1C at >or=90 days after the switch to glyburide-metformin was required for inclusion. Glycemic control, complications, lipid parameters, concomitant medications, and weight were analyzed prior to and following the switch to glyburide-metformin.
The objectives of the present study were to determine the localization of K(ATP) channels in normal retina and to evaluate their potential roles in ischemic preconditioning (IPC) in a rat model of ischemia induced by increased intraocular pressure (IOP). Brown Norway rats were subjected to sublethal 3-, lethal 20- and 40-min ischemia and the functional recovery was evaluated using electroretinography. The time interval between ischemic insults ranged from 1 to 72 h. The effects of K(ATP) channel blockade on IPC protection were studied by treatment with 0.01% glipizide. IPC was mimicked by injection of K(ATP) channel openers of 0.01% (-)cromakalim or 0.01% P1060 72 h before 20-min ischemia. Co-expression of K(ATP) channel subunits Kir6.2/SUR1 was observed in the retinal pigment epithelium, inner segments of photoreceptors, outer plexiform and ganglion cell layers and at the border of the inner nuclear layer. In contrast to a 20- or 40-min ischemia, a 3-min ischemia induced no alteration of the electroretinogram (ERG) and constituted the preconditioning stimulus. An ischemic challenge of 40 min in preconditioned rats induced impairment of retinal function. However, animals preconditioned 24, 48 and 72 h before 20-min ischemia had a significant improvement of the ERG. (-)Cromakalim and P1060 mimicked the effect of IPC. Glipizide significantly suppressed the protective effects of preconditioning. In conclusion, activation of K(ATP) channels plays an important role in the mechanism of preconditioning by enhancing the resistance of the retina against a severe ischemic insult.
glucotrol generic name
A fully automated multipumping flow system (MPFS) using water-soluble CdTe quantum dots (QD) as sensitizers is proposed for the chemiluminometric determination of the anti-diabetic drugs gliclazide and glipizide in pharmaceutical formulations. The nanocrystals acted as enhancers of the weak CL emission produced upon oxidation of sulphite by Ce(IV) in acidic medium, thus improving sensitivity and expanding the dynamical analytical concentration range. By interacting with the QD, the two analytes prevented their sensitizing effect yielding a chemiluminescence quenching of the Ce(IV)-SO(3)(2-)CdTe QD system. The pulsed flow inherent to MPFS assured a fast and efficient mixing of all solutions inside the flow cell, circumventing the need for a reaction coil and facilitating the monitoring of the short-lived generated chemiluminescent species. QD crystal size, concentration and spectral region for measurement were investigated.