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Pharmacokinetics of dirlotapide in the dog
Author(s) -
MERRITT D. A.,
LYNCH M. P.,
KING V. L.
Publication year - 2007
Publication title -
journal of veterinary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.527
H-Index - 60
eISSN - 1365-2885
pISSN - 0140-7783
DOI - 10.1111/j.1365-2885.2007.00862.x
Subject(s) - beagle , bioavailability , pharmacokinetics , volume of distribution , zoology , plasma clearance , distribution (mathematics) , plasma concentration , chemistry , oral administration , medicine , pharmacology , biology , mathematics , mathematical analysis
An overview of the pharmacokinetics of dirlotapide in beagle dogs is presented. The following mean parameters were observed after a 0.3‐mg/kg i.v. dose of dirlotapide: plasma clearance of 7.8 mL/min/kg and volume of distribution of 1.3 L/kg. Following single oral doses of 0.05, 0.3, and 1.0 mg/kg to fed dogs and 0.3 mg/kg to fasted dogs using the commercial formulation, mean C max of 7.5, 46, 97, and 31 ng/mL, respectively, were observed at mean t max of 0.8–2.0 h. AUC and C max increased with increasing dose, but not proportionally. Oral bioavailability was 22–41%. Exposure, as reflected by AUC , was 54% higher in the fed than fasted state. In a 14‐day repeated‐dose study (0.3 mg/kg dose), the mean accumulation ratio was 3.7. In a 3‐month study at doses of 0.4–2.5 mg/kg, accumulation ratios ranged from 2.0 to 6.7 at day 29 and from 1.3 to 4.1 at day 87. In summary, dirlotapide exhibited low clearance, low first‐pass metabolism, moderate volume of distribution, low‐to‐moderate oral bioavailability, a modest food effect, and variable accumulation. Large interanimal variability in systemic exposure was noted for all routes and doses, but there were no consistent sex differences.