Modelling concentrations of antimicrobial drugs: comparative pharmacokinetics of cephalosporin antimicrobials and accuracy of allometric scaling in food-producing and companion animals.

Femke J Taverne,Johan W Mouton,Ingeborg M Van Geijlswijk,Jaap A Wagenaar,Dick J J Heederik

doi:10.1186/s12917-016-0817-2

Abstract

BackgroundTo optimize antimicrobial dosing in different animal species, pharmacokinetic information is necessary. Due to the plethora of cephalosporin antimicrobials and animal species in which they are used, assessment of pharmacokinetics in all species is unfeasible. In this study we aimed to describe pharmacokinetic data of cephalosporins by reviewing the available literature for food producing and companion animal species. We assessed the accuracy of interspecies extrapolation using allometric scaling techniques to determine pharmacokinetic characteristics of cephalosporins in animal species for which literature data is unavailable. We assessed the accuracy of allometric scaling by comparing the predicted and the published pharmacokinetic value in an animal species/humans not included in the allometric modelling.ResultsIn general, excretion of cephalosporins takes place mainly through renal mechanisms in the unchanged form and volume of distribution is limited in all animal species. Differences in plasma protein binding capacity and elimination half-life are observed but available information was limited. Using allometric scaling, correlations between body weight (BW) and volume of distribution (Vd) and clearance (Cl) were R 2 > 0.97 and R 2 > 0.95 respectively for ceftazidime, ceftiofur, cefquinome and cefepime but not ceftriaxone. The allometric exponent ranged from 0.80 to 1.31 for Vd and 0.83 to 1.24 for Cl. Correlations on half-life ranged from R2 0.07–0.655 (literature) and R2 0.102–0.876 (calculated).ConclusionsAllometric scaling can be applied for interspecies extrapolation of cephalosporin pharmacokinetic parameters Vd and Cl, but not elimination half-life. We hypothesize that the accuracy could be improved by using more refined scaling techniques.Electronic supplementary materialThe online version of this article (doi:10.1186/s12917-016-0817-2) contains supplementary material, which is available to authorized users.

Highlights

To optimize antimicrobial dosing in different animal species, pharmacokinetic information is necessary
Pharmacokinetics of cephalosporins The collected pharmacokinetic data on cephalosporins are presented in Additional file 1: Table S1
Pharmacokinetics of 1st and 2nd generation cephalosporins for the included animal species were available from 15 studies involving 5 different cephalosporins

Summary

Introduction

To optimize antimicrobial dosing in different animal species, pharmacokinetic information is necessary. Antimicrobials are used in both food-producing animals like cattle, pigs, poultry and rabbits and companion animals such as dogs, cats and horses. These animals are known to be potential reservoirs of microorganisms carrying antimicrobial resistance genes [1,2,3,4,5]. Before dosage regimens can be optimized detailed knowledge of the pharmacokinetics of cephalosporins is needed We hypothesize that these data are available for major food-producing animal species such as cattle and pigs, but less so for species like rabbits and companion animals

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