| In Vivo |
Icosabutate (oral gavage; 100 mg/kg; once) accounts for the much higher flow rate of portal vein plasma (522 mL/h) versus mesenteric lymph (0.5 mL/h), that data demonstate that icosabutate is almost entirely taken up through the portal vein (>99%) with only a small fraction of icosabutate being absorbed through the lymphatic pathway in 8‐week old male Wistar rats[1]. Icosabutate ([14‐C]‐icosabutate; oral gavage; 100 mg/kg; once) shows that peak concentrations of radioactivity in most tissues at 4‐8 hours after the dose (except the gastrointestinal tract) with highest concentrations in the liver and kidney, most other tissues contain levels of radioactivity below that in plasma in male albino Wistar rats[1]. Icosabutate (diet administration; 135 mg/kg/day; 5 weeks) markedly improved glucose tolerance after an oral glucose load, significantly reduces AUC (0‐120 minutes) by 60% without affecting body weight, decrease plasma alanine aminotransferase (ALT) levels improves glucose metabolism by a significant decrease in blood glucose, blood hemoglobin A1c, plasma insulin, and HOMA‐IR (-50%, -47%, -76% and -87%, respectively) in mice[1]. Icosabutate (oral adminstration; 112 mg/kg/day; 20 weeks) prevents microvesicular steatosis (-35%) and hepatocellular hypertrophy (-82%), but not macrovesicular steatosis. After 20 weeks of treatment, despite comparable decreases in hepatic inflammatory cell aggregates, only icosabutate reduced hepatic collagen content[1]. Animal Model: 6‐8‐week‐old male ob/ob mice[1] Dosage: 135 mg/kg Administration: 135 mg/kg/day through diet administration; 5 weeks Result: Improved glucose metabolism and insulin resistance. Animal Model: 8‐15‐week‐old male APOE*3Leiden.CETP mice fed a high‐fat and high cholesterol diet[1] Dosage: 112 mg/kg/day Administration: Oral gavage; 20 weeks Result: Improved microvesicular steatosis, hepatic inflammation, and fibrosis.
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