Effects of physiological covariables on pharmacokinetic parameters of clomipramine in a large population of cats after a single oral administration.
This study was conducted to confirm an interindividual variability in pharmacokinetic parameters of clomipramine in a large population of cats and to identify potential covariables that would explain the presence of such pharmacokinetic variability after a single dose of Clomicalm. Clomipramine hydrochloride was administered orally according to a weight-dose chart from 0.32 to 0.61 mg/kg, to 76 cats and five blood samples were then taken by direct venipuncture at 1, 3, 6, 12, and 24 h. Plasma concentrations of clomipramine and desmethylclomipramine (DCMP) were measured by LC-MS/MS. The Standard Two-Stage technique was used to assess differences and detect correlations between pharmacokinetic parameter estimates and individual covariables. A large interindividual variability in all pharmacokinetic parameters (CV% 64-124) was detected. Statistically significant gender-related differences were detected in MR and Cl/F, where female cats had a higher mean MR (0.53) and faster Cl/F (0.36 L/h.kg) than males (0.36 and 0.21 L/h.kg, respectively). No correlation could be found between clomipramine AUC0-24 h or DCMP AUC0-24 h and sedation scores. Further feline studies are required to assess these findings after multiple dosing of clomipramine and DCMP to allow clinical extrapolation.
Lainesse
C
C
Département de Biomédecine Vétérinaire, Faculté de Médecine Vétérinaire, Université de Montréal, St-Hyacinthe, QC, Canada.
Frank
D
D
Beaudry
F
F
Doucet
M
M
D000284:Administration, Oral; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002415:Cats / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D002997:Clomipramine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D008297:Male; D013058:Mass Spectrometry; D015203:Reproducibility of Results
D000929:Antidepressive Agents, Tricyclic; D002997:Clomipramine