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

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.

Ciprofloxacin and norfloxacin pharmacokinetics and prostatic fluid penetration in dogs after multiple oral dosing.

The aims of this study were to assess the pharmacokinetics and pharmacokinetic/pharmacodynamic (PK/PD) indices predictive of clinical outcome of ciprofloxacin (CIP) and norfloxacin (NOR) after multiple oral dosing, and to investigate their penetration into prostatic fluid in dogs. Eight dogs received seven oral doses b.i.d. of NOR (20 mg/kg) and CIP (15 mg/kg). Drug concentrations were determined in blood and in two prostatic fluid samples. Prostatic fluid concentrations were lower than plasma concentrations for both drugs. No statistically significant differences were determined between the pharmacokinetic parameters calculated after the first and seventh doses for either CIP or NOR. The PK/PD indices were found to be useful for predicting bacteriological outcome for fluoroquinolones (area under the disposition curve/minimum inhibitory concentration [MIC] and peak plasma concentration/MIC) and indicate that with this dose regimen CIP presents a more favourable disposition than NOR for successful clinical outcome.