Modelling concentrations of antimicrobial drugs

Comparative pharmacokinetics of cephalosporin antimicrobials and accuracy of allometric scaling in food-producing and companion animals

Femke J. Taverne*, Ingeborg M. van Geijlswijk, Dick J.J. Heederik, Jaap A. Wagenaar, Johan W. Mouton

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

2 Citations (Scopus)

Abstract

Background: To 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 literature data is unavailable. We assessed the accuracy of allometric scaling by comparing the predicted and the published pharmacokinetic value in an animal 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 species/humans not included in the allometric modelling. Results: In 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). Conclusions: Allometric 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.

Original languageEnglish
Article number185
JournalBMC Veterinary Research
Volume12
Issue number1
DOIs
Publication statusPublished - 2016

Fingerprint

cephalosporins
Pets
Cephalosporins
pets
pharmacokinetics
Pharmacokinetics
anti-infective agents
Food
drugs
Pharmaceutical Preparations
half life
Half-Life
animals
ceftriaxone
ceftiofur
Ceftazidime
Ceftriaxone
protein binding
binding capacity
Protein Binding

Keywords

  • Allometric scaling
  • Antimicrobials
  • Cephalosporins
  • Companion animals
  • Food-producing animals
  • Mathematical models
  • Pharmacokinetics

Cite this

Taverne, Femke J. ; van Geijlswijk, Ingeborg M. ; Heederik, Dick J.J. ; Wagenaar, Jaap A. ; Mouton, Johan W. / Modelling concentrations of antimicrobial drugs : Comparative pharmacokinetics of cephalosporin antimicrobials and accuracy of allometric scaling in food-producing and companion animals. In: BMC Veterinary Research. 2016 ; Vol. 12, No. 1.
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abstract = "Background: To 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 literature data is unavailable. We assessed the accuracy of allometric scaling by comparing the predicted and the published pharmacokinetic value in an animal 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 species/humans not included in the allometric modelling. Results: In 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). Conclusions: Allometric 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.",
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Modelling concentrations of antimicrobial drugs : Comparative pharmacokinetics of cephalosporin antimicrobials and accuracy of allometric scaling in food-producing and companion animals. / Taverne, Femke J.; van Geijlswijk, Ingeborg M.; Heederik, Dick J.J.; Wagenaar, Jaap A.; Mouton, Johan W.

In: BMC Veterinary Research, Vol. 12, No. 1, 185, 2016.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Modelling concentrations of antimicrobial drugs

T2 - Comparative pharmacokinetics of cephalosporin antimicrobials and accuracy of allometric scaling in food-producing and companion animals

AU - Taverne, Femke J.

AU - van Geijlswijk, Ingeborg M.

AU - Heederik, Dick J.J.

AU - Wagenaar, Jaap A.

AU - Mouton, Johan W.

PY - 2016

Y1 - 2016

N2 - Background: To 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 literature data is unavailable. We assessed the accuracy of allometric scaling by comparing the predicted and the published pharmacokinetic value in an animal 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 species/humans not included in the allometric modelling. Results: In 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). Conclusions: Allometric 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.

AB - Background: To 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 literature data is unavailable. We assessed the accuracy of allometric scaling by comparing the predicted and the published pharmacokinetic value in an animal 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 species/humans not included in the allometric modelling. Results: In 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). Conclusions: Allometric 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.

KW - Allometric scaling

KW - Antimicrobials

KW - Cephalosporins

KW - Companion animals

KW - Food-producing animals

KW - Mathematical models

KW - Pharmacokinetics

U2 - 10.1186/s12917-016-0817-2

DO - 10.1186/s12917-016-0817-2

M3 - Article

VL - 12

JO - BMC Veterinary Research

JF - BMC Veterinary Research

SN - 1746-6148

IS - 1

M1 - 185

ER -