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


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 R(2) 0.07-0.655 (literature) and R(2) 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.
The Netherlands Veterinary Medicines Authority (SDa), Yalelaan 114, 3584 CM, Utrecht, The Netherlands. f.j.taverne@uu.nl.|Institute for Risk Assessment Sciences, Utrecht University, Yalelaan 2, 3584 CM, Utrecht, The Netherlands. f.j.taverne@uu.nl.|Pharmacy Department, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 106, 3584 CM, Utrecht, The Netherlands. f.j.taverne@uu.nl.
Femke J
FJ
Taverne
The Netherlands Veterinary Medicines Authority (SDa), Yalelaan 114, 3584 CM, Utrecht, The Netherlands.|Pharmacy Department, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 106, 3584 CM, Utrecht, The Netherlands.
Ingeborg M
IM
van Geijlswijk
The Netherlands Veterinary Medicines Authority (SDa), Yalelaan 114, 3584 CM, Utrecht, The Netherlands.|Institute for Risk Assessment Sciences, Utrecht University, Yalelaan 2, 3584 CM, Utrecht, The Netherlands.
Dick J J
DJ
Heederik
The Netherlands Veterinary Medicines Authority (SDa), Yalelaan 114, 3584 CM, Utrecht, The Netherlands.|Department of Infectious Diseases & Immunology, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, 3584 CL, Utrecht, The Netherlands.|Central Veterinary Institute, Wageningen UR, Houtribweg 39, 8221 RA, Lelystad, The Netherlands.
Jaap A
JA
Wagenaar
The Netherlands Veterinary Medicines Authority (SDa), Yalelaan 114, 3584 CM, Utrecht, The Netherlands.|Department of Medical Microbiology and Infectious Diseases, Erasmus MC, Wytemaweg 80, 3015 CN, Rotterdam, The Netherlands.
Johan W
JW
Mouton
D000818:Animals; D000829:Animals, Domestic / Q000097:blood* / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D001835:Body Weight / Q000502:physiology; D002511:Cephalosporins / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D006801:Humans; D008954:Models, Biological; D019155:Veterinary Drugs / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics
D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D019155:Veterinary Drugs
Allometric scaling; Antimicrobials; Cephalosporins; Companion animals; Food-producing animals; Mathematical models; Pharmacokinetics