title: Pharmacokinetics of clomipramine in dogs following single-dose intravenous and oral administration.
abstract: OBJECTIVE
  To determine pharmacokinetics of clomipramine and its principle metabolite (desmethylclomipramine) in the plasma of dogs after IV or oral administration of a single dose.
  
  
  METHODS
  6 male and 6 female Beagles.
  
  
  METHODS
  Clomipramine was administered IV (2 mg/kg), PO (4 mg/kg) after food was withheld for 15 hours, and PO (4 mg/kg) within 25 minutes after dogs were fed. Plasma clomipramine and desmethylclomipramine concentrations were measured by use of a gas chromatography with mass-selection method.
  
  
  RESULTS
  Time to peak plasma concentrations of clomipramine and desmethylclomipramine following oral administration was 1.2 hours. For clomipramine, after IV administration, elimination half-life was 5 hours, mean residence time was 3 hours, and plasma clearance was 1.4 L/h/kg. Values for mean residence time and terminal half-life following oral administration were similar to values obtained following IV administration, and systemic bioavailability was approximately 20% for clomipramine and 140% for desmethylclomipramine, indicating fast absorption of clomipramine from the gastrointestinal tract and extensive first-pass metabolism. Administration of clomipramine with food did not alter the area under the concentration versus time curve for desmethylclomipramine but resulted in a 25% increase for clomipramine. Clomipramine and desmethylclomipramine were extensively bound (> 96%) to serum proteins. There were no significant differences in area under the concentration versus time curve between male and female dogs.
  
  
  CONCLUSIONS
  Results indicate that there should not be any clinically important differences in efficacy regardless of whether clomipramine is administered with or without food.
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: R P
authors.initials: RP
authors.lastname: Hotz
authors.forename: R D
authors.initials: RD
authors.lastname: Fisch
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D001798:Blood Proteins / Q000502:physiology; D002849:Chromatography, Gas / Q000662:veterinary; D002997:Clomipramine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004285:Dogs / Q000378:metabolism*; D005260:Female; D007275:Injections, Intravenous / Q000662:veterinary; D008297:Male; D014462:Ultrafiltration
chemical_list: D000929:Antidepressive Agents, Tricyclic; D001798:Blood Proteins; C012273:desmethylclomipramine; D002997:Clomipramine