Active Ingredients: Orlistat
The work reported in this manuscript was performed in accordance with UK law, as detailed in the Animals Scientific Procedures Act 1986. Two separate studies were conducted the combination study was performed subsequent to the first study in a separate cohort of animals.
Approximately 2 weeks before the start of each study, animals were housed singly in polypropylene cages with wire-grid floors so food spillage could be determined.
Each cage contained an appropriate amount of paper bedding for warmth and environmental enrichment and to provide an area for animals to get off the wire-grid floor.
In each study, animals underwent a baseline period of dosing, where each animal was dosed once daily orally with vehicle by gavage. Toward the end of this baseline phase, animals were allocated by a statistician into treatment groups, balanced in regard to baseline body weight and daily food and water intake.
Drug dosing was timed to begin at the onset of the dark phase. Rats, feeding jars and water bottles were weighed to the nearest 0.
Blood samples 4-hour fasted were taken from the lateral tail vein during the baseline phase and on days 14 and 28, 4 hours after dosing.
On day 21, animals were dosed and immediately placed in metabolism cages for a 7-hour period.
Food was not present in the metabolism cages, although animals had free access to water. At the end of the study day 29, carcasses were saved for body-composition analysis. All dosing was via the oral route by gavage.
Blood samples were taken during the baseline phase and on days 16 and 30 after an overnight fast. At the conclusion of the test, food was returned.
On day 34, the experiments concluded, and the carcasses were saved for body-composition analysis. All compounds were dosed orally in a vehicle of aqueous 0. All doses were corrected for salt where appropriate. Subsequently, plasma was assayed for content of one or more of the following: glucose, insulin, leptin, adiponectin, glycerol, and triacylglycerol TAG content.
Female Wistar rats were exposed to a recorded daily.