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. 2014:2014:789353.
doi: 10.1155/2014/789353. Epub 2014 Nov 6.

A population pharmacokinetic approach to describe cephalexin disposition in adult and aged dogs

Ana Paula Prados  1 , Paula Schaiquevich  2 , Verónica Kreil  1 , Agustina Monfrinotti  1 , Pamela Quaine  1 , Lisa Tarragona  1 , Ruben Hallu  1 , Marcela Rebuelto  1
Affiliations

A population pharmacokinetic approach to describe cephalexin disposition in adult and aged dogs

Ana Paula Prados et al. Vet Med Int. 2014.

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.

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Figures

Figure 1
Figure 1
Concentration versus time profiles of cephalexin. Symbols represent the observed data for two representative animals studied in two occasions: green line, individual estimation.
Figure 2
Figure 2
Goodness of fit plots. (a) Observed versus population predicted and (b) observed versus individual predicted values. The continuous line is the identity line, (c) scatter plot of weighted residuals versus time and (d) scatter plot of weighted residuals versus predicted cephalexin concentrations.
Figure 3
Figure 3
Visual predictive check. The figure shows the 90% prediction intervals obtained by simulation using the final model. The light blue areas are the 90% confidence intervals for the median, 5th percentile, and the 90th percentile of the simulated data. Circles represent observed data.
See this image and copyright information in PMC

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