Effects Of Glipizide Research Articles

Effects of CYP2C9*3 and *13 alleles on the pharmacokinetics and pharmacodynamics of glipizide in healthy Korean subjects

Glipizide is a second-generation sulfonylurea antidiabetic drug. It is principally metabolized to inactive metabolites by genetically polymorphic CYP2C9 enzyme. In this study, we investigated the effects of CYP2C9*3 and *13 variant alleles on the pharmacokinetics and pharmacodynamics of glipizide. Twenty-four healthyKorean volunteers (11 subjects with CYP2C9*1/*1, 8 subjects with CYP2C9*1/*3, and 5 subjects with CYP2C9*1/*13) were recruited for this study. They were administered a single oral dose of glipizide 5mg. The plasma concentration of glipizide was quantified for pharmacokinetic analysis and plasma glucose and insulin concentrations were measured as pharmacodynamic parameters. The results represented that CYP2C9*3 and *13 alleles significantly affected the pharmacokinetics of glipizide. In subjects with CYP2C9*1/*3 and CYP2C9*1/*13 genotypes, the mean AUC0-∞ were increased by 44.8% and 58.2%, respectively (both P < 0.001), compared to those of subjects with CYP2C9*1/*1 genotype, while effects of glipizide on plasma glucose and insulin levels were not significantly different between CYP2C9 genotype groups. In conclusion, individuals carrying thedefective CYP2C9*3 and CYP2C9*13 alleles have markedly elevated plasma concentrations of glipizide compared with CYP2C9*1/*1 wild-type.

Comparative study of In-Vivo effects of Glipizide and Metformin HCl on plasma concentration of Aminophylline in healthy rabbits

Comparative study of <i>In-Vivo</i> effects of Glipizide and Metformin HCl on plasma concentration of Aminophylline in healthy rabbits

Effects of Glipizide on the Pharmacokinetics of Carvedilol after Oral and Intravenous Administration in Rats

This study was designed to investigate the effects of glipizide on the pharmacokinetics of carvedilol after oral or intravenous administration of carvedilol in rats. Clinically carvedilol and glipizide can be prescribed for treatment of cardiovascular diseases as the complications of diabetes, and then, Carvedilol and glipizide are all substrates of CYP2C9 enzymes. Carvedilol was administered orally or intravenously without or with oral administration of glipizide to rats. The effects of glipizide on cytochrome P450 (CYP) 2C9 activity and P-gp activity were also evaluated. Glipizide inhibited CYP2C9 activity in a concentration-dependent manner with 50% inhibition concentration (IC50) of 18 μM. Compared with the control group, the area under the plasma concentration-time curve (AUC) was significantly increased by 33.0%, and the peak concentration (Cmax) was significantly increased by 50.0% in the presence of glipizide after oral administration of carvedilol. Consequently, the relative bioavailability (R.B.) of carvedilol was increased by 1.13- to 1.33-fold and the absolute bioavailability (A.B.) of carvedilol in the presence of glipizide was increased by 36.8%. After intravenous administration, compared to the control, glipizide could not significantly change the pharmacokinetic parameters of carvedilol. Therefore, the enhanced oral bioavailability of carvedilol may mainly result from inhibition of CYP2C9- mediated metabolism rather than both P-gp-mediated efflux in the intestinal or in the liver and renal elimination of carvedilol by glipizide.

The effect of glipizide, metformin and rosiglitazone on nontraditional cardiovascular risk factors in newly diagnosed patients with type 2 diabetes mellitus

Background: Diabetes mellitus (DM) is recognized as a major risk factor for cardiovascular disease (CVD). Traditional cardiovascular risk factors (CVRFs) alone cannot explain excess risk for CVD associated with DM; nontraditional CVRFs also may play an important role. Aim: To study the effects of glipizide, metformin and rosiglitazone on traditional [lipid profile, lipoprotein Lp(a)] and nontraditional CVRFs [homocysteine (Hcy), soluble Vascular Cell Adhesion Molecule (sVCAM-1), malonyldialdehyde (MDA) and nitric oxide (NO) levels]. Setting and Design: An open-label, randomized, parallel group study was conducted in the departments of pharmacology, internal medicine and biochemistry of Lady Hardinge Medical College. Materials and Methods: Ninety newly diagnosed type 2 DM patients were randomly assigned to glipizide, metformin or rosiglitazone treatment daily for a duration of 12 weeks. If needed, the dosages were titrated upward to achieve fasting plasma glucose <126 mg /dL. Plasma glucose, glycosylated hemoglobin (HbA1c), lipid profile, body mass index (BMI), Lp(a), Hcy, sVCAM-1, MDA and NO were estimated both before and after treatment. Statistical Analysis: Data were analyzed using paired Student’s t-test within each group. Results and Conclusion: All the three drugs led to significant decrease in HbA1c, fasting and postprandial plasma glucose levels. Glipizide lowered body weight, BMI, total cholesterol (P < 0.05), low density lipoprotein cholesterol (LDL-C) (P < 0.01) and MDA levels (P < 0.05). Metformin reduced body weight (P < 0.01), BMI (P < 0.01), LDL-C, very low density lipoprotein cholesterol (VLDL-C) and improved high density lipoprotein cholesterol (HDL-C); however, it raised Hcy levels (P < 0.01). Rosiglitazone treatment increased

Short-time effects of glipizide, an ATP-sensitive potassium channel inhibitor, on cardiopulmonary hemodynamics and global oxygen transport in healthy and endotoxemic sheep

Short-time effects of glipizide, an ATP-sensitive potassium channel inhibitor, on cardiopulmonary hemodynamics and global oxygen transport in healthy and endotoxemic sheep

Effects of glipizide on glucose metabolism and muscle content of the insulin-regulatable glucose transporter (GLUT 4) and glycogen synthase activity during hyperglycaemia in type 2 diabetic patients.

To examine whether sulphonylureas influence hyperglycaemia-induced glucose disposal and suppression of hepatic glucose production (HGP) in type 2 diabetes mellitus, a 150-min hyperglycaemic (plasma glucose 14 mmol/l) clamp with concomitant somatostatin infusion was used in eight type 2 diabetic patients before and after 6 weeks of glipizide (GZ) therapy. During the clamp a small replacement dose of insulin was given (0.15 mU/kg per min). Isotopically determined glucose-induced glucose uptake was similar before and after GZ administration which led to improved glycaemic control (basal plasma glucose 12.2 +/- 1.3 vs 8.9 +/- 0.7 mmol/l; P < 0.01). Glucose-induced suppression of HGP was, however, more pronounced during GZ treatment (0.96 +/- 0.14 vs 1.44 +/- 0.20 mg/kg per min; P < 0.02). Following GZ treatment hyperglycaemia failed to stimulate glycogen synthase activity. Moreover, GZ resulted in a significant increase in the immunoreactive abundance of the insulin-regulatable glucose transport protein (GLUT 4) (P < 0.02). In conclusion, these results suggest that GZ therapy in type 2 diabetic patients enhances hepatic sensitivity to hyperglycaemia, while glucose-induced glucose uptake remains unaffected. In addition, GZ tends to normalize the activity of glycogen synthase and increases the content of GLUT 4 protein in skeletal muscle.

Pharmacokinetics and Effects of Glipizide in Healthy Volunteers

The efficacy of glipizide was assessed in 12 healthy volunteers following single-dose administration of a rapid-release soft gelatin capsule containing the drug in solution (2.5 and 5mg), in conventional tablet (2.5 and 5mg) and intravenous (2.5mg) formulations. Meals were given 15 and 180 minutes after the drug. The bioavailability of glipizide from the capsule was complete, and interindividual variation in absorption kinetics was reduced following the capsule; this formulation also promoted higher peak concentrations (629 ± 53 vs 412 ± 34 µg/L with the 5mg dose) and a shorter time to peak (41 ± 6 vs 95 ± 18 min, respectively). The AUC0–45min and AUC0–180min of serum glipizide were higher, and the AUC0–45min of serum insulin was greater after the capsule. Only the capsule and the intravenous dose completely abolished the blood glucose increase after breakfast. It appears that the new capsule formulation increases the absorption rate of glipizide, and it seems possible that this might have therapeutic benefit.

Effects of Glipizide on β-Endorphin Secretions in Response to Hyperglycaemia in Obese Cafeteria Rats

Regulation of blood glucose involves the integration of the central nervous system with both hormonal and neural mechanisms. Considerable evidence suggests that beta-endorphin is involved in the regulation of feeding in experimental animals and man. Previous studies have shown that beta-endorphin plays an important role during hyperglycaemia. Glipizide has been shown to increase glucose metabolism by both pancreatic and extrapancreatic actions. This study indicates that glipizide may exert its pharmacological action in obese cafeteria rats through a modification of beta-endorphin secretions via central and peripheral mechanisms.

Effects of Glipizide on β-Endorphin Concentration in the Brain of Genetically Diabetic (db/db) Mice

Sulphonylurea drugs have been shown to augment glucose metabolism by both pancreatic and extrapancreatic actions. The regulation of glucose involves a modification of beta-endorphin secretions via central and peripheral mechanisms. beta-Endorphin participates in the regulation of feeding and is implicated both in obesity and diabetes mellitus. This study shows that glipizide could exert its pharmacological action in genetically diabetic (db/db) mice via beta-endorphin secretions by a central mechanism.

Extrapancreatic Effects of a Sulphonylurea

The effects of glipizide on the absorption of glucose and d-xylose were studied in six type II diabetics on diet treatment alone. Glipizide was given intravenously (12 micrograms/kg at 0 min) or orally (5 mg at -30 min). Oral glucose (15 g) and xylose (25 g) loads were given at zero time. Glipizide stimulated insulin secretion and reduced glucose and xylose levels significantly with both routes of administration. The suppression of xylose levels lasted longer after oral than after intravenous administration of the drug. It is suggested that part of the influence of glipizide on postprandial glucose levels may represent interference with absorptive mechanisms.

Bioavailability, pharmacokinetics and effects of glipizide in type 2 diabetics.

The pharmacokinetics of glipizide were studied in 6 type 2 diabetics following single dose intravenous administration of Img, and oral administration of 2.5 mg as a solution, a 2.5 mg tablet and a 5 mg tablet. The serum concentrations of the drug were measured by high pressure liquid chromatography. Glipizide showed a rapid distribution fitting a 2-compartment model. The distribution volume at assumed distribution equilibrium was small (10L), and the elimination half-life was short (2 to 4 hours). Gastrointestinal bioavailability was 100%. In one patient, glipizide absorption from tablets was retarded due to delayed tablet disintegration and drug dissolution. Each dose of glipizide reduced blood glucose levels rapidly in all patients.

Influence of food intake on the absorption and effect of glipizide in diabetics and in healthy subjects.

The influence of a standardized breakfast on the single dose (5 mg) kinetics and effects of glipizide was examined in 9 healthy volunteers and in 14 diabetics not previously exposed to a sulfonylurea. In the volunteers, glipizide caused an increase in plasma insulin and a reduction in blood glucose both during continued fasting and when the drug was taken with the breakfast. Food intake did not influence the peak concentration, the elimination half-life or the bioavailability of the drug. However, food intake significantly delayed the absorption of glipizide by about 0.5 h. In the patients. glipizide produced a significant increase in plasma glucose in response to the meal. Starting at breakfast and for 45 min thereafter serum glipizide concentrations were significantly higher when the drug was taken 0.5 h before the meal, than when ingested concurrently with it. With the former treatment, the increase in plasma insulin occurred earlier and the blood glucose reduction was pronouncedly greater than with the latter treatment. As the absorption of glipizide may be delayed by concurrent breakfast, this may help to explain, why the administration of glipizide 0.5 h before breakfast led to a more appropriate relation between the serum concentration of the drug and the metabolic impact of the meal, thereby promoting more appropriate insulin release and better glucose disposition than after concurrent intake of the drug and breakfast.

Effects of Glipizide and Food Intake on the Blood Levels of Glucose and Insulin in Diabetic Patients

ABSTRACT. The blood levels of glucose and insulin were monitored in 15 patients with non‐ketotic maturity‐onset diabetes mellitus given a single 5 mg oral dose of a novel sulfonylurea drug, glipizide, together with, and 30 min prior to, a standardized breakfast meal. In addition, the effect of the meal only was examined. The mean preprandial levels of blood glucose and plasma insulin on the three occasions were similar. Following glipizide administration, the early postprandial increment of blood glucose was reduced, and there was a subsequent decrease to values below the preprandial level. Both the decrease and the reduction of the early increase were significantly more marked when the drug was given 30 min prior to than together with the meal. Apparently, this did not result from a stronger effect of the drug on insulin release when given before than together with the meal, as the plasma insulin levels and the corresponding concentration curve areas did not differ. Rather, the difference was due to a more optimal timing between insulin release and the blood glucose increment evoked by the meal. In addition, there seemed to be only a minor interindividual variation in the bioavailability of the drug, as its effect on insulin levels varied rather little. Hence, 5 mg of glipizide three times daily 30 min before meals can be recommended as a standard regimen.

Clinical evaluation of glipizide in patients with diabetes mellitus

SummaryThe hypoglycaemic and insulin-liberating effects of glipizide were demonstrated using a test meal in 1.5 patients with maturity onset diabetes. Glipizide effectively controlled the post-prandial hyperglycaemic peak starting 30 minutes after administration, and total amounts of insulin liberated and insulin assays after 60 minutes were significantly different from those after placebo. In a second series of tests on 30 patients with maturity onset diabetes, glycaemia and glycosuria were significantly reduced after 1.5 days and the results were even better after 2 months. No significant differences were detected in any of the laboratory parameters measured.