Effects on Metabolic Blood and Tissue Parameters in Conscious Rats Multiple Dose Study

Effects on Metabolic Blood and Tissue Parameters in Conscious Rats (Multiple Dose Study) 

For studying the side effect potential of candidate compounds on blood triglycerides and cholesterol as well as on metabolic rate, insulin sensitivity and body weight development multiple dose studies for at least 1 week are necessary. For transcriptional active compounds like the PPAR agonist (peroxisome 

At the end of such multiple dose studies the animals are killed in terminal anesthesia and maximal blood collection is possible. Therefore, not only the target metabolic parameters (e.g. glucose, lactate, free fatty acids, triglycerides, cholesterol) but also other parameters, which reflect intermediary metabolism (e.g. keton bodies, urea, uric acid) as well as safety parameters (e.g. ASAT, ALAT, AP, LDH) can be determined by clinical chemistry. 

Eight rats per group (lean control, obese control, and dose groups) are treated with the candidate compound in various doses for up to 6 weeks. According to the pharmacokinetic profile (ti/2) the candidate compound is administered once or twice a day by gavage. If the stability of the compound is sufficient the candidate compound can also be administered by food admixture. Food and water consumption as well as body weight are measured at least once a week. Blood glucose is determined in 10 il blood samples collected from the tip 

The differences of the metabolic blood parameters of the treated groups are calculated against both control groups (lean and obese), which have received the vehicle only. The metabolic tissue parameters at the end of the study are assessed between the two control and treatment groups. 

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