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week) compared to placebo animals that gained a mean
of 10.6% body weight. In addition, average food intake
was decreased by 54%, cholesterol decreased by 51%,
and fecal fat increased from 1.86% to 7.50%. Following
the weight loss phase, body weight was maintained in
dogs receiving dirlotapide (3) over a 28-day period at
dosages of 0.1–0.35 mg/kg (Table 8).
In conclusion, a very potent MTP inhibitor, dirlotapide
(3), has been discovered and profiled. The robust effica-
cy has been shown in animal models. The unique
ADME properties of dirlotapide (3) minimized the drug
exposure systemically; therefore a better safety profile is
expected in clinical trials.
14. Hickman, M. A.; Lundy, K. M.; Morgan, B. P.
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