title: Biologic activity of dirlotapide, a novel microsomal triglyceride transfer protein inhibitor, for weight loss in obese dogs.
abstract: Dirlotapide is a novel microsomal triglyceride transfer protein inhibitor intended for the treatment and management of obesity in dogs. The biologic effects of dirlotapide, weight loss, decreased food intake, increased fecal fat, decreased serum cholesterol, and body composition, were evaluated in a controlled, blinded study. Sixteen obese beagles were randomized to treatment with placebo (n = 4) or dirlotapide (n = 12) following a 2-week acclimation period in which baseline data were collected. The dirlotapide dose, adjusted to produce weight loss for 3 months and then stabilize body weight for 1 month (weight management), produced a significant difference (expressed as a percentage of baselines) in weekly weight loss, food intake, fecal fat, serum cholesterol concentration, and body composition (measured by dual energy X-ray absorptiometry) compared with placebo treatment (P < 0.05). The initial dirlotapide dosage of 0.5 mg/kg (10 times the initial label dose) resulted in a high rate of weight loss (3.3% weekly) and anorexia, emesis, and loose stools for some dogs. A 25% dose reduction (mean dosage: 0.36 mg/kg) followed by biweekly 25% dose adjustments based on individual weight loss, produced 1-2% weekly weight loss and total weight loss of 18.8% in 12 weeks at a final mean dosage of 0.41 mg/kg (range: 0.15-0.60); a dosage range of 0.10-0.34 mg/kg stabilized body weight. Body weight changes for placebo-treated dogs were -0.8% to +0.9% weekly; total weight gain during the weight loss phase was 10.6%. No apparent change in food intake, percentage of fecal fat, and serum cholesterol was observed in the placebo group. Food intake and body weight increased when dirlotapide was discontinued. Dirlotapide produced weight loss by both reducing appetite (about 90% of the weight loss activity) and by increasing fecal fat excretion (about 10% of the weight loss activity).
authors.affiliation: Pfizer Inc, Veterinary Medicine Research and Development, Kalamazoo, MI 49001-0199, USA. jody.wren@pfizer.com
authors.forename: J A
authors.initials: JA
authors.lastname: Wren
authors.forename: V L
authors.initials: VL
authors.lastname: King
authors.forename: S L
authors.initials: SL
authors.lastname: Campbell
authors.forename: M A
authors.initials: MA
authors.lastname: Hickman
mesh_terms: D015502:Absorptiometry, Photon; D000273:Adipose Tissue; D000284:Administration, Oral; D000818:Animals; D019440:Anti-Obesity Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001823:Body Composition; D001835:Body Weight; D002219:Carbamates / Q000008:administration & dosage / Q000627:therapeutic use*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors*; D004283:Dog Diseases / Q000188:drug therapy* / Q000473:pathology; D004285:Dogs; D004435:Eating; D005260:Female; D007211:Indoles / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D009765:Obesity / Q000188:drug therapy / Q000662:veterinary*; D016896:Treatment Outcome
chemical_list: D019440:Anti-Obesity Agents; D002219:Carbamates; D002352:Carrier Proteins; D007211:Indoles; C106092:microsomal triglyceride transfer protein; C521290:dirlotapide