IngentaConnect Effects of physiological covariables on pharmacokinetic parameter...

Authors: LAINESSE, C.¹; FRANK, D.²; BEAUDRY, F.¹; DOUCET, M.¹

Source: Journal of Veterinary Pharmacology & Therapeutics, Volume 30, Number 2, April 2007 , pp. 116-126(11)

Abstract:

Lainesse, C., Frank, D., Beaudry, F., Doucet, M. Effects of physiological covariables on pharmacokinetic parameters of clomipramine in a large population of cats after a single oral administration. J. vet. Pharmacol. Therap.30, 116-126.

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 AUC_0-24h or DCMP AUC_0-24h and sedation scores. Further feline studies are required to assess these findings after multiple dosing of clomipramine and DCMP to allow clinical extrapolation.

Document Type: Research article

DOI: 10.1111/j.1365-2885.2007.00826.x

Affiliations: 1: Département de Biomédecine Vétérinaire, Faculté de Médecine Vétérinaire, Université de Montréal, St-Hyacinthe, QC, Canada 2: Département de Sciences Cliniques, Faculté de Médecine Vétérinaire, Université de Montréal, St-Hyacinthe, QC, Canada

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