title: A population pharmacokinetic approach to describe cephalexin disposition in adult and aged dogs.
abstract: This study was conducted in order to characterize the pharmacokinetics of orally administered cephalexin to healthy adult and aged dogs, using a population pharmacokinetic approach. Two hundred and eighty-six cephalexin plasma concentrations obtained from previous pharmacokinetic studies were used. Sex, age, pharmaceutical formulation, and breed were evaluated as covariates. A one-compartment model with an absorption lag-time (Tlag) best described the data. The final model included age (adult; aged) on apparent volume of distribution (Vd/F), apparent elimination rate (ke/F), and Tlag; sex (female; male) on ke/F, and breed (Beagle; mixed-breed) on Vd/F. Addition of the covariates to the model explained 78% of the interindividal variability (IIV) in Vd/F, 36% in ke/F, and 24% in Tlag, respectively. Formulation did not affect the variability of any of the pharmacokinetic parameters. Tlag was longer, whereas Vd/F and ke/F were lower in aged compared to adult animals; in female aged dogs ke/F was lower than in male aged dogs; however, the differences were of low magnitude. Different disposition of cephalexin may be expected in aged dogs.
authors.affiliation: Farmacología, Facultad de Ciencias Veterinarias, Universidad de Buenos Aires. Chorroarín 280, 1427 Buenos Aires, Argentina.
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Prados
authors.affiliation: Unidad de Farmacocinética Clínica-CONICET, Hospital de Pediatría JP Garrahan, Combate de los Pozos 1881, 1245 Buenos Aires, Argentina.
authors.forename: Paula
authors.identifier: 0000-0002-2568-4731
authors.initials: P
authors.lastname: Schaiquevich
authors.affiliation: Farmacología, Facultad de Ciencias Veterinarias, Universidad de Buenos Aires. Chorroarín 280, 1427 Buenos Aires, Argentina.
authors.forename: Verónica
authors.initials: V
authors.lastname: Kreil
authors.affiliation: Farmacología, Facultad de Ciencias Veterinarias, Universidad de Buenos Aires. Chorroarín 280, 1427 Buenos Aires, Argentina.
authors.forename: Agustina
authors.initials: A
authors.lastname: Monfrinotti
authors.affiliation: Farmacología, Facultad de Ciencias Veterinarias, Universidad de Buenos Aires. Chorroarín 280, 1427 Buenos Aires, Argentina.
authors.forename: Pamela
authors.initials: P
authors.lastname: Quaine
authors.affiliation: Farmacología, Facultad de Ciencias Veterinarias, Universidad de Buenos Aires. Chorroarín 280, 1427 Buenos Aires, Argentina.
authors.forename: Lisa
authors.initials: L
authors.lastname: Tarragona
authors.affiliation: Farmacología, Facultad de Ciencias Veterinarias, Universidad de Buenos Aires. Chorroarín 280, 1427 Buenos Aires, Argentina.
authors.forename: Ruben
authors.initials: R
authors.lastname: Hallu
authors.affiliation: Farmacología, Facultad de Ciencias Veterinarias, Universidad de Buenos Aires. Chorroarín 280, 1427 Buenos Aires, Argentina.
authors.forename: Marcela
authors.identifier: 0000-0001-9567-1365
authors.initials: M
authors.lastname: Rebuelto