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

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.

Pharmacokinetics and bioavailability of cefquinome and ceftriaxone in premature calves

“…The binding rate of CFQ to plasma proteins was found to be approximately 11% in buffalo calves (Venkatachalam & Dumka, 2015). Another study reported that the excretion extent of CFQ correlated with glomerular filtration rate in dogs; however, data in calves are not available (Taverne, van Geijlswijk, Heederik, Wagenaar, & Mouton, 2016). The rapid elimination of the drug in premature calves could be due to increased cardiac output, which would lead to an increase in glomerular filtration rate (Stritzke, Thomas, Amin, Fusch, & Lodha, 2017).…”

Vorkommen der interstitiellen Nephritis bei Schweinen

“…It might be due to different endogenous factors, different causing agents and/ or pathogenetic factors or due to differences in antimicrobial treatment. Many antimicrobial agents are excreted through the kidney and thereby may lead to changes in the kidney (19,32). Additionally, Zwald et al (35) reported a higher use of antimicrobial treatment in conventionally dairy herds in comparison to organically herds.…”

Characteristics, Properties and Analytical Methods of Cefquinome - A Review

“…Taverne FJ et al, 33 determined the pharmacokinetic data of cephalosporins by reviewing the available literature for food producing and companion animal species. They assessed the accuracy of allometric scaling in food-producing and companion animals.…”