Absorption, distribution, metabolism, and excretion of dirlotapide in the dog.
Three once-daily oral doses of 0.2 mg/kg [(14)C]dirlotapide were administered to beagle dogs to study the absorption, distribution, metabolism, and excretion of dirlotapide. Mean (14)C recovered at 2.5 and 4.5 h after the last dose was 90%. Mean (14)C in urine, bile, and feces was <1%, 1.7%, and 56% of the dose, respectively. In tissues, 26% of the (14)C dose was present in the gastrointestinal tract, 6.0% in liver, and <1% each in kidney, gall bladder, heart, and brain. To further characterize drug disposition, a single 2.5-mg/kg oral dose of [(14)C]dirlotapide was administered to beagle dogs. More than 84% of the dose had been eliminated by 72 h in feces, with 21% of the dose present in feces as parent dirlotapide. Less than 1% of the dose was excreted in urine. In bile collected during the first 24-h postdose from three dogs, 32% and 11% of the (14)C dose was present in samples from male and female dogs, respectively. Based upon metabolite profiling of plasma, excreta, and bile samples, dirlotapide was extensively metabolized to more than 20 metabolites. Biliary/fecal excretion and the potential for enterohepatic recycling of metabolites are suggested.
Merritt
D A
DA
Pfizer Animal Health, Veterinary Medicine Research and Development, Kalamazoo, MI 49001, USA. dawn.a.merritt@pfizer.com
Bessire
A J
AJ
Vaz
A D
AD
Sams
J P
JP
Lynch
M P
MP
D000284:Administration, Oral; D000818:Animals; D019440:Anti-Obesity Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D001646:Bile / Q000378:metabolism; D002219:Carbamates / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D002250:Carbon Radioisotopes / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D004285:Dogs / Q000378:metabolism*; D005260:Female; D007211:Indoles / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D008297:Male; D014018:Tissue Distribution
D019440:Anti-Obesity Agents; D002219:Carbamates; D002250:Carbon Radioisotopes; D007211:Indoles; C521290:dirlotapide