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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Extrapancreatic activity of the sulfonylurea, glipizide, was evaluated in the neonatal streptozotocin-induced rat model of noninsulin-dependent diabetes. Two day old Wistar rats were given a bolus of streptozotocin (90 mg/kg i.p.) to cause noninsulin-dependent diabetes; these animals became severely glucose intolerant and eventually developed a cardiomyopathy characterized by reduced heart rate, contractility and cardiac output. Male littermates injected with citrate buffer served as nondiabetic controls. At four weeks of age, the nondiabetic and NIDD rats were administered by gavage either glipizide (2.5 mg/kg) or the methyl cellulose vehicle. Throughout the treatment protocol, no difference in the degree of glucose intolerance was observed between the glipizide-treated and vehicle-treated animals. Glipizide therapy also was ineffective in improving plasma insulin levels, which were significantly depressed in the diabetic group. Yet, animals treated with glipizide for one year exhibited improved myocardial contractile function relative to the vehicle-fed or ad lib fed diabetic animals. Heart rate was significantly elevated and there was a tendency for both the rate of relaxation and contractility to be elevated in sulfonylurea-treated group. Glipizide also reduced the degree of insulin resistance in the heart. Since these changes occur in the absence of changes in glucose tolerance or insulin levels, the heart appears to be very sensitive to the direct effects of the sulfonylureas.
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PMID:Effects of chronic glipizide treatment on the NIDD heart. 840 18

The pharmacokinetics and pharmacodynamics of glipizide were evaluated in 20 patients with non-insulin-dependent diabetes mellitus (NIDDM). The group consisted of 12 obese subjects (seven women, five men; mean +/- SD age, 53.5 +/- 8.5 years; total body weight (TBW), 95.5 +/- 17.2 kg; percentage > IBW (ideal body weight), 57.8 +/- 31.7%); and eight nonobese subjects (two women, six men; age, 57.8 +/- 11.7 years; TBW, 80.8 +/- 9.9 kg; percentage > IBW, 15.6 +/- 10.3%). After a 2-week antidiabetic drug-free period, patients were started on glipizide therapy for 12 weeks. Glipizide dosages were titrated to achieve specified therapeutic goals or a maximum daily dose of 40 mg. Glipizide pharmacokinetics were assessed by serum concentrations obtained during a 24-h pharmacokinetic evaluation performed after the first 5-mg dose (SD) and after 12 weeks of chronic therapy (CD). Glipizide pharmacodynamics were evaluated with serum glucose, insulin, and C-peptide responses to Sustacal tolerance test done at baseline, after SD, and after CD. No statistically significant differences in the SD pharmacokinetic parameters (Tmax = 3.1 +/- 1.2 vs. 2.8 +/- 1.6 h; Cmax = 332.5 +/- 92.5 vs. 420.8 +/- 142 g/L; area under the curve extrapolated to infinity (AUCI) = 2,598.3 +/- 1,148 vs. 3,138.9 +/- 1,847 g/h/L; oral clearance/bioavailability (CL/F), 2.3 +/- 1.0 vs. 2.0 +/- 1.0 L/h; volume of distribution/bioavailability (V/F), 19.5 +/- 4.4 vs. 17.2 +/- 4.3 L; t1/2 = 5.0 +/- 2.3 vs. 5.2 +/- 2.0 h) were observed between the obese and nonobese groups, respectively. The pharmacokinetic parameters assessed under CD conditions were also closely matched in the two groups. No differences in glucose responses to Sustacal challenge at baseline, SD, and CD (AUC0-->4.glucose:baseline, 52.3 +/- 18.0 vs. 44.9 +/- 9.8; SD, 50.4 +/- 20.9 vs. 36.1 +/- 11.0; CD, 37.8 +/- 10.7 vs. 36.6 +/- 8.5 mM/h) were noted between the obese and nonobese groups, respectively. However, glucose concentrations increased more and decreased to a smaller extent after SD in the obese as compared to nonobese subjects. Mean fasting serum insulin and C-peptide concentrations were not statistically different between the two groups. However, obese subjects exhibited higher fasting insulin (114.0 +/- 69 vs. 68.8 +/- 52 pM) at week 12 evaluation and C-peptide concentrations (0.83 +/- 0.2 vs. 0.63 +/- 0.2 nM) after SD as compared to the nonobese group. A smaller percentage increase in C peptide in response to Sustacal challenge was observed in the obese compared to the nonobese subjects (baseline, 60 +/- 25 vs. 117 +/- 117; SD, 119 +/- 39 vs. 193 +/- 149; and CD, 97 +/- 56 vs. 163 +/- 67%). In summary, the influence of obesity on glipizide pharmacokinetics appeared to be of little clinical significance. The observed differences in pharmacodynamics require further evaluation.
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PMID:The effects of obesity on the pharmacokinetics and pharmacodynamics of glipizide in patients with non-insulin-dependent diabetes mellitus. 884 22

Glipizide is a second generation of sulphonylurea compound, effective in lowering of blood glucose, well-tolerated as well as safe during long-term treatment. Glipizide is the agent characterized by rapid pharmacological action. It is indicated both in monotherapy and combined treatment with insulin or biguanides. This drug is particularly indicated in diabetes treatment in elderly patients due to short time of action as well as lack of hyperinsulinemic effect. Data in literature suggest that glipizide combined with insulin is much more effective in the induction of remission in recent diagnosed diabetes when compared to intensive insulin therapy.
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PMID:[Glipizide--a short-acting sulphonylurea derivative]. 899 34

Hypoglycaemic sulfonamides differ in their properties, which vary in clinical importance. The potency of sulfonamide has increased with the generations. However, this potency is compensated in practice by the dose prescribed, which is much smaller for recent generations. The half-life is a far more important property. The effective action period is correlated with half-life but is much longer. The action period for "short-term" sulfonamides is < or = 24 h (tolbutamide, glipizide) and can exceed 24 h for "long-term" sulfonamides (e.g. glibenclamide). Metabolism and elimination reduce the risk of accumulation. All sulfonamides are metabolised more than 95% by the liver. The metabolites are inactive except for one from glibenclamide. As a function of their action period and possibly of intrinsic properties, some sulfonamides more than others (e.g. glibenclamide) affect fasting hepatic glucose production, which is particularly increased early in the day in non-insulin-dependent diabetic patients because of a circadian drop in insulin sensitivity (dawn phenomenon). Finally, in chronic administration, all sulfonamides cause a progressive desensitisation of the beta cell, which responds by an insulin secretion peak only during food intake. This condition indicates the unuselessness of sulfonamide fractionation and, contrary to the classic notion, the low risk of hypoglycaemia after a meal is skipped. The ideal product would be a sulfonamide with high potency and an ultra-short half-life, but capable of maintaining plasma concentrations for 24 h (which might seem incompatible except in continuous administration). Moreover, it would exert its action at relatively low levels of insulinaemia and be completely metabolisable. Glipizide in its osmotic oral form (Ozidia) satisfies all these conditions since it is a very potent sulfonamide with a quite short half-life but with intestinal delivery up to 16 h after administration because of its osmotic principle. It controls fasting glycaema better than ordinary glipizide and at least as well as glibenclamide by acting on hepatic glucose production. Compared to glibenclamide, it has the advantage of generation this effect at lower levels of insulinaemia. In comparison with normal glipizide, it allows identical control for lower postprandial inslinaemias, which is proof of its powerful inductive effect on insulin sensitivity.
Diabetes Metab 1997 Nov
PMID:[Pharmacokinetics of hypoglycemic sulfonamides: Ozidia, a new concept]. 946 23

In diabetes, the links between long-term complications and chronic hyperglycaemia and the risk of hypoglycaemia during intensive treatment have been well-documented. However, the potential short- or long-term benefits of glycaemic control on quality of life and cognitive functions have generally been reported as minimal or nil. Patients do not perceive the connection between better glycaemic control and quality of life. The potential advantages of Ozidia, whether in terms of glycaemic control, tolerance or ease of use, suggest that this treatment may provide improved quality of life. Two studies have investigated this possibility. The first, carried out over a 16-week period in the United States, was a randomised double-blind Ozidia vs placebo study in 594 non-insulin-dependent (NIDDM) diabetic patients to evaluate the respective influences of glycaemic control, symptoms of hyperglycaemia and side-effects of treatment on quality of life. The results were important, indicating a decrease in short-term clinical symptoms and an improvement in the quality of life, in correlation with decreased HbA1C. The quality of life of NIDDM patients can be improved by stricter glycaemic control, and thus can modify in the choice of therapeutic strategies and cost-benefit evaluation of intensive glycaemic control. The second study now under way in France concerns an evaluation of the quality of life of NIDDM patients before and after treatment with Ozidia. More than 600 diabetologists are involved, and the study should include 1,500 patients. The purpose is to show that Ozidia effectively improves quality of life by encouraging treatment compliance and improving treatment effectiveness. Thanks to self-monitoring of glycaemia, patients can measure the efficacy of their treatment regularly at various times of the day. A dose 5 to 15 mg/day of Ozidia is administered in this open 12-week study. The results will not be available before the end of 1997.
Diabetes Metab 1997 Nov
PMID:[Quality of life and non-insulin-dependent diabetes]. 946 24

Etiopathogenesis of diabetes mellitus is bipolar. On one hand there occurs impairment in beta-cell function caused by genetic factors or abnormal development during fetal period. On the other hand defects of peripheral insulin action are also of significant importance. The bipolarity is also expressed by changing relationship between genetic and environmental factors. Insulin release is connected with closing ATP-dependent kalium channel, a structure closely connected with sulfonylurea receptors. Several receptors may be distinguished: SUR1 in Langerhans isles and SUR2 in heart (SUR2A) and vessel smoot muscles (SUR2B). In the treatment of insulin release disorders sulfonylureas are still of significant importance though repaglinid and phenyloalanine derivates also have some clinical importance. Within sulfonylurea derivates there have been developed some preparations of slow drug release (Glibenese GITS, Diaprel MR). One daily dose of Glibenese GITS and lower tendency to hypoglycaemia favour acceptation of the therapy by the patients what is also important for their quality of life. Quality of life is now regarded as important as obtaining good indices of diabetes control.
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PMID:[Drugs stimulating insulin release. Importance of their use for improving glycemia, safety and quality of life in diabetes mellitus type 2]. 1090 60

Patients with diabetes (type 1 or type 2) live shorter because of the long-term complications of hyperglycemia. One of the most important aims of therapy in diabetic subjects is delay in the development of long-term diabetes complications. However, another important aim of therapy in diabetic patients is the use of drugs, which not only delay the time of long-term complications development but also improve the quality of life. The paper presents the results of studies on quality of life in diabetic subjects basing on contemporary literature. In patients with type 1 diabetes mellitus a quality of life decreases gradually with the duration of diabetes. The influence of intensive insulin therapy on quality of life is minimal or absent. In UKPDS study no differences in quality of live between conventionally or intensively treated patients were observed. In subjects with macrovascular complications the quality of life is significantly worse. Generally, the authors of UKPDS suggested that better glycemic control is not associated with better quality of life. Only Testa and Simonsen demonstrated that type 2 diabetic subjects treated by new "intelligent" drug--glipizide GITS (Glibenese GITS) is associated not only with better metabolic control but also with better quality of life.
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PMID:[The effect of improved glycemic control on quality of life in patients with type I and type II diabetes]. 1192 56

K(ATP) channels are important for insulin secretion and depolarization of vascular smooth muscle. In view of the importance of drugs affecting K(ATP) channels in the treatment of diabetes, we investigated the effects of these channels on splanchnic blood perfusion in general and pancreatic islet blood flow in particular. We treated anesthetized Sprague-Dawley rats with the K(ATP) channel openers diazoxide or NNC 55-0118 or the K(ATP) channel closer glipizide. Both diazoxide and NNC 55-0118 dose-dependently increased total pancreatic and islet blood flow in the presence of moderate hyperglycemia, but had no effects on the blood perfusion of other splanchnic organs. Diazoxide markedly lowered the mean arterial blood pressure and thus increased vascular conductance in all organs studied. NNC 55-0118 had much smaller effects on the blood pressure. Glipizide did not affect total pancreatic blood flow, but decreased islet blood flow by 50% in the presence of hypoglycemia. We conclude that K(ATP) channels actively participate in the blood flow regulation of the pancreatic islets and that substances affecting such channels may also influence islet blood flow.
Diabetes 2003 Aug
PMID:K(ATP) channels and pancreatic islet blood flow in anesthetized rats: increased blood flow induced by potassium channel openers. 1288 21

Glipizide and rosiglitazone are widely used to treat Type 2 diabetes. In order to investigate drug-drug protein binding interaction between glipizide and rosiglitazone, a method was developed and validated for simultaneously determining the free (unbound) fraction of glipizide and rosiglitazone in plasma employing equilibrium dialysis for the separation of free drug and liquid chromatography-tandem mass spectrometry (LC-MS/MS) for quantitation. Post-dialysis human plasma or buffer samples of 0.2 ml were extracted using a liquid-liquid extraction procedure and analyzed by a high performance liquid chromatography electrospray tandem mass spectrometer system. The compounds were eluted isocratically on a Zorbax SB-Phenyl column, ionized using an atmospheric pressure electrospray ionization source and analyzed in positive ion mode with multiple reaction monitoring. The ion transitions monitored were m/z 446-->321 for glipizide, m/z 358-->135 for rosiglitazone, and m/z 271-->155 for tolbutamide (internal standard, IS). The chromatographic run time was 5 min per injection, with retention times of 2.3, 3.4 and 2.3 min for glipizide, rosiglitazone and IS, respectively. The calibration curves of glipizide and rosiglitazone were over the range of 1-2000 ng/ml (r(2)>0.9969) in the combined matrix of human plasma and isotonic sodium phosphate buffer (1:1, v/v). The inter-assay precision and accuracy of the quality control samples were <10.9% of coefficient of variability and >93.5% and 94.5% of nominal concentration for glipizide and rosiglitazone, respectively. The lower limit of quantitation of both glipizide and rosiglitazone was 1.0 ng/ml. Both glipizide and rosiglitazone bound to plasma protein extensively (>99% bound). Glipizide and rosiglitazone free fraction averaged 0.678+/-0.071 and 0.389+/-0.061%, respectively, at plasma concentration of 1000 ng/ml. This developed method proves reproducible and sensitive and its application to clinical samples is also reported.
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PMID:Simultaneous determination of glipizide and rosiglitazone unbound drug concentrations in plasma by equilibrium dialysis and liquid chromatography-tandem mass spectrometry. 1475 95

We describe a patient with Stevens-Johnson syndrome (erythema multiforme major) associated with an increase in glipizide dosage administration. Glipizide is a second-generation sulfonylurea commonly used to treat patients with noninsulin-dependent diabetes mellitus. Although several reports have documented Stevens-Johnson syndrome caused by first-generation sulfonylureas, our case appears to be the first report of a second-generation sulfonylurea associated with Stevens-Johnson syndrome.
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PMID:Stevens-Johnson syndrome associated with glipizide therapy. 1680 Feb 77


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