Pharmacokinetics of dirlotapide in the dog.
J Vet Pharmacol Ther
; 30 Suppl 1: 24-32, 2007 Aug.
Article
em En
| MEDLINE
| ID: mdl-17567512
ABSTRACT
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.
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Base de dados:
MEDLINE
Assunto principal:
Carbamatos
/
Fármacos Antiobesidade
/
Cães
/
Indóis
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Vet Pharmacol Ther
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Estados Unidos