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Prednisolone in Dogs-Plasma Exposure and White Blood Cell Response

Ekstrand, Carl and Pettersson, Helena and Gehring, Ronette and Hedeland, Mikael and Adolfsson, Sara and Lilliehöök, Inger (2021). Prednisolone in Dogs-Plasma Exposure and White Blood Cell Response. Frontiers in Veterinary Science. 8 , 666219
[Research article]

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Abstract

Glucocorticoids such as prednisolone are commonly used in dogs but there is sparse quantitative pharmacokinetic and pharmacodynamic information of this drug in this species. The objective of this study was to quantitatively characterize the concentration-effect relationship for prednisolone in dogs on neutrophil and lymphocyte trafficking and cortisol suppression. Nine beagles, 2-12 years old and part of a group for teaching/research were used in a 4-way crossover experiment including two treatments, active or placebo, administered either per os (PO) or intravenously (IV). Plasma was analyzed for prednisolone and cortisol using ultra-high performance liquid chromatography - tandem mass spectrometry. Leucocyte counts were performed in whole blood. Data was then analyzed by non-linear mixed effect modeling to estimate pharmacokinetic and pharmacodynamic parameters. After administration of prednisolone sodium succinate IV, the typical value (between subject variation) for total body prednisolone clearance was 1,370 ml/h center dot kg (13.4%). The volumes of the central and peripheral compartment were 2,300 ml/kg (10.7%) and 600 ml/kg (16.0%), respectively. The terminal plasma half-life was 1.7 h. The prednisolone plasma concentration producing 50% of the maximum response was 10 ng/mL (90.3%), 22.5 ng/ml (52.3%) and 0.04 ng/mL (197.3%) for neutrophil, lymphocyte and cortisol response, respectively. The administered dose (1 mg/kg) increased neutrophil and decreased lymphocyte numbers but not over the entire dosage interval of 24 h, due to the short half-life. However, glucocorticoids have a wide range of responses. An anti-inflammatory response due to altered gene transcription might have a longer duration. Future studies on the anti-inflammatory potency together with data presented are needed to optimize future dosage recommendations in dogs.

Authors/Creators:Ekstrand, Carl and Pettersson, Helena and Gehring, Ronette and Hedeland, Mikael and Adolfsson, Sara and Lilliehöök, Inger
Title:Prednisolone in Dogs-Plasma Exposure and White Blood Cell Response
Series Name/Journal:Frontiers in Veterinary Science
Year of publishing :2021
Volume:8
Article number:666219
Number of Pages:10
Publisher:FRONTIERS MEDIA SA
ISSN:2297-1769
Language:English
Publication Type:Research article
Article category:Scientific peer reviewed
Version:Published version
Copyright:Creative Commons: Attribution 4.0
Full Text Status:Public
Subjects:(A) Swedish standard research categories 2011 > 4 Agricultural Sciences > 403 Veterinary Science > Clinical Science
Keywords:canine, glucocorticoid, pharmacokinetics, pharmacodynamics, immune-suppression
URN:NBN:urn:nbn:se:slu:epsilon-p-112698
Permanent URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-p-112698
Additional ID:
Type of IDID
DOI10.3389/fvets.2021.666219
Web of Science (WoS)000664305600001
ID Code:25352
Faculty:VH - Faculty of Veterinary Medicine and Animal Science
University Animal Hospital
Department:(VH) > Department of Biomedical Science and Veterinary Public Health
(VH) > Dept. of Clinical Sciences
University Animal Hospital (UAH)
Deposited By: SLUpub Connector
Deposited On:15 Sep 2021 14:25
Metadata Last Modified:15 Sep 2021 14:31

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