Drug delivery to rodents: how to deal with body mass and water intake fluctuations?

ABSTRACTIntroductionAnimal models are used to test the safety and efficacy of drugs. They are often administered to rodents in the drinking water, but it has some limitations, such as the drug stability, variations of water consumption and body mass. We investigated telmisartan (TEL) stability in mice drinking water by UV spectrophotometry, and if water intake and body mass fluctuations change drug ingestion.MethodsFemale C57BL/6 mice at two months old, were fed for eight weeks with a purified AIN93M diet, or a high-fat high-sucrose diet (HFHS). TEL 5 mg/Kg/day was administered ad libitum to mice in the drinking water during three weeks concomitant with diets, summing 11 weeks of diet feeding.ResultsUV spectrophotometry could detect TEL at the wavelength of 300 nm, and it remained stable in mice drinking water for seven days, at the concentration expected. Mice gain weight after eight weeks on high-fat high-sucrose diet feeding, and TEL 5 mg/kg/day in the drinking water for three weeks reduced it. TEL did not change water intake. Not adjusting TEL concentration weekly would lead to a higher intake of TEL by mice.DiscussionWe demonstrated that body mass and water intake fluctuations significantly change the amount of drug that the animal receive, and it would add a bias to the experiment. TEL remains stable for at least seven days in wrapped mice water bottles in the animal care facility, and UV spectrophotometry proved to be a simple and low-cost method to detect TEL in mice drinking water.