Pharmacokinetics of clomipramine in dogs following single-dose and repeated-dose oral administration.
Am J Vet Res
; 61(1): 80-5, 2000 Jan.
Article
en En
| MEDLINE
| ID: mdl-10630784
ABSTRACT
OBJECTIVE:
To determine pharmacokinetics of clomipramine and its principle metabolite (desmethylclomipramine) in the plasma of dogs following single-dose and repeated-dose oral administration at various dosages. ANIMALS 9 male and 9 female Beagles. PROCEDURES Clomipramine was administered orally at a dose of 1, 2, or 4 mg/kg to 3 male and 3 female dogs, first as a single dose and then, after an interval of 14 days, twice daily for 10 days. Plasma clomipramine and desmethylclomipramine concentrations were measured by use of a gas chromatography with mass-selection method.RESULTS:
Dose-related accumulation was detected following repeated-dose administration. Accumulation ratios after administration of clomipramine at dosages of 1, 2, and 4 mg/kg twice daily were 1.4, 1.6, and 3.8, respectively, for clomipramine and 2.1, 3.7, and 7.6, respectively, for desmethylclomipramine. Terminal half-life increased slightly (1.6-fold for clomipramine and 1.2-fold for desmethylclomipramine) with repeated-dose administration but remained short in all groups (< or = 4 hours). Steady state was reached within 4 days in all animals. Ratios of the areas under the concentration versus time curves from time 0 to 12 hours for clomipramine and desmethylclomipramine were 3.9, 3.1, and 1.5 after repeated administration at dosages of 1, 2, and 4 mg/kg every 12 hours, respectively. Areas under the concentration versus time curve, mean residence times, and terminal half-lives were not significantly different between male and female dogs. CONCLUSIONS AND CLINICAL RELEVANCE Repeated administration of clomipramine results in higher concentrations of clomipramine than desmethylclomipramine in dogs.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Clomipramina
/
Perros
/
Antidepresivos Tricíclicos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Am J Vet Res
Año:
2000
Tipo del documento:
Article
País de afiliación:
Suiza