Advanced search
1 file | 786.81 KB

Pharmacokinetic and urinary profiling reveals the prednisolone/cortisol ratio as a valid biomarker for prednisolone administration

Author
Organization
Abstract
Background: In Europe, synthetic corticosteroids are not allowed in animal breeding for growth-promoting purposes. Nevertheless, a high prevalence of non-compliant urine samples was recently reported for prednisolone, however, without any indication of unauthorized use. Within this context, 20 beta-dihydroprednisolone and the prednisolone/cortisol ratio have been suggested as potential tools to discriminate between exogenous and endogenous urinary prednisolone. In this study, the validity of these strategies was verified by investigating the plasma pharmacokinetic and urinary excretion profiles of relevant glucocorticoids in bovines, subjected to exogenous prednisolone treatment or tetracosactide hexaacetate administration to induce endogenous prednisolone formation. Bovine urine and plasma samples were analysed by liquid chromatography and mass spectrometry. Results: Based on the plasma pharmacokinetics and urinary profiles, 20 beta-dihydroprednisolone was confirmed as the main prednisolone-derived metabolite, being detected in the biological fluids of all 12 bovines (plasma AUC(0-inf) of 121 h mu g L-1 and urinary concentration > 0.695 mu g L-1). However, this metabolite enclosed no potential as discriminative marker as no significant concentration differences were observed upon exogenous prednisolone treatment or tetracosactide hexaacetate administration under all experimental conditions. As a second marker tool, the prednisolone/cortisol ratios were assessed along the various treatments, taking into account that endogenous prednisolone formation involves the hypothalamic-pituitary-adrenal axis and is associated with an increased cortisol secretion. Significantly lower ratios were observed in case of endogenous prednisolone formation (i.e. ratios ranging from 0.00379 to 0.129) compared to the exogenous prednisolone treatment (i.e. ratios ranging from 0.0603 to 36.9). On the basis of these findings, a discriminative threshold of 0.260 was proposed, which allowed classification of urine samples according to prednisolone origin with a sensitivity of 94.2% and specificity of 99.0%. Conclusion: The prednisolone/cortisol ratio was affirmed as an expedient strategy to discriminate between endogenous and exogenous prednisolone in urine. Although the suggested threshold value was associated with high specificity and sensitivity, a large-scale study with varying experimental conditions is designated to optimize this value.
Keywords
ADRENAL AXIS, BOVINE URINE, GLUCOCORTICOIDS, METABOLITES, EXCRETION, COWS, Glucocorticoids, Prednisolone, Screening tools, Prednisolone/cortisol, ratio, 20 beta-dihydroprednisolone, Adrenocorticotropic hormone, Urinary, profiling

Downloads

  • Van Meulebroek et al., BMC, 2017.pdf.06ktf24.pdf
    • full text
    • |
    • open access
    • |
    • PDF
    • |
    • 786.81 KB

Citation

Please use this url to cite or link to this publication:

Chicago
Van Meulebroek, Lieven, Nathalie De Clercq, Julie Vanden Bussche, Mathias Devreese, Eric Fichant, Philippe Delahaut, Siska Croubels, and Lynn Vanhaecke. 2017. “Pharmacokinetic and Urinary Profiling Reveals the Prednisolone/cortisol Ratio as a Valid Biomarker for Prednisolone Administration.” Bmc Veterinary Research 13.
APA
Van Meulebroek, L., De Clercq, N., Vanden Bussche, J., Devreese, M., Fichant, E., Delahaut, P., Croubels, S., et al. (2017). Pharmacokinetic and urinary profiling reveals the prednisolone/cortisol ratio as a valid biomarker for prednisolone administration. BMC VETERINARY RESEARCH, 13.
Vancouver
1.
Van Meulebroek L, De Clercq N, Vanden Bussche J, Devreese M, Fichant E, Delahaut P, et al. Pharmacokinetic and urinary profiling reveals the prednisolone/cortisol ratio as a valid biomarker for prednisolone administration. BMC VETERINARY RESEARCH. 2017;13.
MLA
Van Meulebroek, Lieven, Nathalie De Clercq, Julie Vanden Bussche, et al. “Pharmacokinetic and Urinary Profiling Reveals the Prednisolone/cortisol Ratio as a Valid Biomarker for Prednisolone Administration.” BMC VETERINARY RESEARCH 13 (2017): n. pag. Print.
@article{8540647,
  abstract     = {Background: In Europe, synthetic corticosteroids are not allowed in animal breeding for growth-promoting purposes. Nevertheless, a high prevalence of non-compliant urine samples was recently reported for prednisolone, however, without any indication of unauthorized use. Within this context, 20 beta-dihydroprednisolone and the prednisolone/cortisol ratio have been suggested as potential tools to discriminate between exogenous and endogenous urinary prednisolone. In this study, the validity of these strategies was verified by investigating the plasma pharmacokinetic and urinary excretion profiles of relevant glucocorticoids in bovines, subjected to exogenous prednisolone treatment or tetracosactide hexaacetate administration to induce endogenous prednisolone formation. Bovine urine and plasma samples were analysed by liquid chromatography and mass spectrometry. 
Results: Based on the plasma pharmacokinetics and urinary profiles, 20 beta-dihydroprednisolone was confirmed as the main prednisolone-derived metabolite, being detected in the biological fluids of all 12 bovines (plasma AUC(0-inf) of 121 h mu g L-1 and urinary concentration {\textrangle} 0.695 mu g L-1). However, this metabolite enclosed no potential as discriminative marker as no significant concentration differences were observed upon exogenous prednisolone treatment or tetracosactide hexaacetate administration under all experimental conditions. As a second marker tool, the prednisolone/cortisol ratios were assessed along the various treatments, taking into account that endogenous prednisolone formation involves the hypothalamic-pituitary-adrenal axis and is associated with an increased cortisol secretion. Significantly lower ratios were observed in case of endogenous prednisolone formation (i.e. ratios ranging from 0.00379 to 0.129) compared to the exogenous prednisolone treatment (i.e. ratios ranging from 0.0603 to 36.9). On the basis of these findings, a discriminative threshold of 0.260 was proposed, which allowed classification of urine samples according to prednisolone origin with a sensitivity of 94.2\% and specificity of 99.0\%. 
Conclusion: The prednisolone/cortisol ratio was affirmed as an expedient strategy to discriminate between endogenous and exogenous prednisolone in urine. Although the suggested threshold value was associated with high specificity and sensitivity, a large-scale study with varying experimental conditions is designated to optimize this value.},
  articleno    = {236},
  author       = {Van Meulebroek, Lieven and De Clercq, Nathalie and Vanden Bussche, Julie and Devreese, Mathias and Fichant, Eric and Delahaut, Philippe and Croubels, Siska and Vanhaecke, Lynn},
  issn         = {1746-6148},
  journal      = {BMC VETERINARY RESEARCH},
  keyword      = {ADRENAL AXIS,BOVINE URINE,GLUCOCORTICOIDS,METABOLITES,EXCRETION,COWS,Glucocorticoids,Prednisolone,Screening tools,Prednisolone/cortisol,ratio,20 beta-dihydroprednisolone,Adrenocorticotropic hormone,Urinary,profiling},
  language     = {eng},
  pages        = {12},
  title        = {Pharmacokinetic and urinary profiling reveals the prednisolone/cortisol ratio as a valid biomarker for prednisolone administration},
  url          = {http://dx.doi.org/10.1186/s12917-017-1158-5},
  volume       = {13},
  year         = {2017},
}

Altmetric
View in Altmetric
Web of Science
Times cited: