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.

Population Pharmacokinetic Study of Cefazolin Used Prophylactically in Canine Surgery for Susceptibility Testing Breakpoint Determination

“…Moreover, through a Pop PK approach with a sufficient knowledge of covariates, it is possible to predict a typical PK profile for any given patient, allowing the definition of the correctness of the treatment ( Concordet et al, 2004 ). In veterinary medicine, over the last decades, many Pop PK studies regarding AMDs have been performed in dogs ( Regnier et al, 2003 ; Zhao et al, 2012 ; Prados et al, 2014 ; Hnot et al, 2015 ; Papich, 2017 ), but no study has been carried out with cefazolin. Starting from these assumptions, the aim of the study was to determine the Pop PK profile of cefazolin administered prophylactically at 25 mg/kg by intravenous (IV) bolus 30 min before surgery in a representative canine population to identify whether covariates such as sex, age, body weight (BW), breed, health status, creatinine level and surgery time, have an influence on cefazolin disposition.…”

Pharmacokinetics of Immediate and Sustained Release Cephalexin Administered by Different Routes to Llamas (Lama glama)

“…The microbiological assay is useful for determining the plasma concentrations of those antimicrobial agents that are not transformed into active metabolites, as almost all beta-lactams, including cephalexin. The methodology used in this study has been validated in our laboratory and was used for previous cephalexin pharmacokinetic characterizations in goats [ 11 ], cattle [ 10 ], and dogs [ 2 , 3 ]. The immediate release cephalexin dosage was chosen according to those used in previous pharmacokinetic studies in ruminant species as cows and goats [ 7 , 8 , 10 , 11 ]; meanwhile, the dosage of long-acting cephalexin was the one indicated by the manufacturer for other species (feline, canine, bovine, ovine, and pigs).…”

“…Cephalexin may be administered by the oral or parenteral routes, and currently available commercial formulations may provide an immediate or a sustained release of the drug, thus prolonging the duration of the antibacterial activity (long-acting formulations). Cephalexin pharmacokinetics has been described in several domestic species, such as dogs [ 2 , 3 ], horses [ 4 ], and ruminants [ 5 – 11 ]; however, pharmacokinetic reports on conventional and long-acting cephalexin pharmacokinetics in llama are lacking. The purposes of this study were to investigate the pharmacokinetics of cephalexin formulated as an immediate and sustained release commercial formulation when administered to healthy adult llamas as single bolus by the intravenous (IV), intramuscular (IM), and subcutaneous (SC) routes, to determine the MIC of cephalexin against some Escherichia coli and coagulase-positive staphylococci isolated from llamas, and to apply the PK/PD modelling approach, so that effective dosage recommendations for this species can be made.…”