Disease relevance of Galida

• AZ 242 dose-dependently reduced the hypertriglyceridemia, hyperinsulinemia, and hyperglycemia of ob/ob diabetic mice [1].
• AstraZeneca plc is developing tesaglitazar, an oral dual peroxisome proliferator-activated receptor alpha/gamma agonist, for the potential improvement of dyslipidemia and glycemic control in type 2 diabetic patients [2].

Psychiatry related information on Galida

• A second group received the same HC supplement along with tesaglitazar (T) 0.5 micromol/kg diet (T group) [3].

High impact information on Galida

• Tesaglitazar, a novel dual peroxisome proliferator-activated receptor alpha/gamma agonist, dose-dependently improves the metabolic abnormalities associated with insulin resistance in a non-diabetic population [4].
• RESULTS: A 1.0-mg dose of tesaglitazar reduced fasting triglycerides (the primary endpoint) by 37% (95% CI: -43% to -30%; p<0.0001), non-HDL-cholesterol by 15% (95% CI: -20% to -10%; p<0.0001) and NEFA by 40% (95% CI: -51% to -27%; p<0.0001), and increased HDL-cholesterol by 16% (95% CI: 8 to -24%; p<0.0001) [4].
• Peroxisome proliferator-activated receptor (PPAR) activation induces tissue-specific effects on fatty acid uptake and metabolism in vivo--a study using the novel PPARalpha/gamma agonist tesaglitazar [5].
• To test this hypothesis directly, we examined the effect of the novel PPARalpha/gamma agonist tesaglitazar on whole-body insulin sensitivity and NEFA clearance into epididymal white adipose tissue (WAT), red gastrocnemius muscle, and liver in rats with dietary-induced insulin resistance [5].
• In vitro, in reporter gene assays, AZ 242 activated human PPARalpha and PPARgamma with EC(50) in the micro molar range [1].

Biological context of Galida

• AZ 242, a novel PPARalpha/gamma agonist with beneficial effects on insulin resistance and carbohydrate and lipid metabolism in ob/ob mice and obese Zucker rats [1].
• This study evaluated the effects of food on tesaglitazar pharmacokinetics [6].
• Systemic exposure to tesaglitazar was unaffected by food intake [6].
• Tesaglitazar absorption was rapid, with maximum plasma concentration (C(max)) at approximately 1 h postdose, and the absolute bioavailability was approximately 100%, suggesting no, or negligible, first-pass metabolism [7].
• Plasma protein binding of tesaglitazar was high ( approximately 99.9%), and the mean blood-plasma partitioning ratio was 0.66, suggesting low affinity for red blood cells [7].

Anatomical context of Galida

• We present pharmacodynamic effects of AZ 242, a novel peroxisome proliferator activated receptor (PPAR)alpha/gamma agonist [1].
• In addition, tesaglitazar reduced inflammatory markers, including plasma SAA levels, the number of adhering monocytes, and nuclear factor kappaB-activity in the vessel wall [3].

Associations of Galida with other chemical compounds

• This study examined the effect of tesaglitazar (Galida), a novel, dual-acting peroxisome proliferator-activated receptor alpha/gamma agonist, on lipid and glucose metabolism in patients with evidence of insulin resistance [4].
• Approximately 20% of the dose was recovered unchanged after either administration route, resulting in a renal clearance of 0.030 l/h. Most of the radioactivity in urine was identified as acyl glucuronide of tesaglitazar [7].
• Similar numbers of adverse events occurred in the tesaglitazar < or = 1.0 mg, placebo, and pioglitazone arms, but there was an increasing frequency of discontinuations due to pre-specified hematologic and clinical-chemistry criteria with tesaglitazar doses > or = 1.0 mg [8].

Gene context of Galida

• In anesthetized, 5-h fasted, obese Zucker rats, tesaglitazar reduced hepatic TG secretion by 47%, increased plasma TG clearance by 490%, and reduced very low-density lipoprotein (VLDL) apolipoprotein CIII content by 86%, compared with obese controls [9].

Analytical, diagnostic and therapeutic context of Galida

• In an open, randomized, 2-way crossover study, 20 healthy men received tesaglitazar 1 mg during fasting and after a high-fat, high-calorie breakfast [6].
• The present work demonstrates that tesaglitazar ameliorates these abnormalities and enhances insulin sensitivity in this animal model [9].
• Tesaglitazar is a dual-acting PPARalpha/gamma agonist currently being investigated in phase III clinical trials as an alternative treatment for insulin resistance and the characteristic dyslypidemia of type 2 diabetes [10].

References