title: Pharmacokinetics of clomipramine in dogs following single-dose and repeated-dose oral administration.
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.
  
  
  METHODS
  9 male and 9 female Beagles.
  
  
  METHODS
  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
  Repeated administration of clomipramine results in higher concentrations of clomipramine than desmethylclomipramine in dogs.
authors.affiliation: Novartis Animal Health, Werk Rosenthal, Basel, Switzerland.
authors.forename: J N
authors.initials: JN
authors.lastname: King
authors.forename: M P
authors.initials: MP
authors.lastname: Maurer
authors.forename: B O
authors.initials: BO
authors.lastname: Altmann
authors.forename: G A
authors.initials: GA
authors.lastname: Strehlau
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002849:Chromatography, Gas / Q000662:veterinary; D002997:Clomipramine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics*; D004285:Dogs / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006207:Half-Life; D008297:Male; D011897:Random Allocation; D012737:Sex Factors
chemical_list: D000929:Antidepressive Agents, Tricyclic; C012273:desmethylclomipramine; D002997:Clomipramine