Prednisolone in Dogs-Plasma Exposure and White Blood Cell Response.

Autor:	Ekstrand C; Division of Pharmacology and Toxicology, Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, Uppsala, Sweden., Pettersson H; Division of Clinical Pathology, Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden.; Clinical Pathology Laboratory, University Animal Hospital, Swedish University of Agricultural Sciences, Uppsala, Sweden., Gehring R; Division of Pharmacology and Toxicology, Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, Uppsala, Sweden.; Division of Veterinary and Comparative Pharmacology, Department of Population Health Sciences, Utrecht University, Utrecht, Netherlands., Hedeland M; Department of Chemistry, Environment and Feed Hygiene, National Veterinary Institute, Uppsala, Sweden.; Department of Medicinal Chemistry, Uppsala University, Uppsala, Sweden., Adolfsson S; Division of Pharmacology and Toxicology, Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, Uppsala, Sweden., Lilliehöök I; Division of Clinical Pathology, Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden.; Clinical Pathology Laboratory, University Animal Hospital, Swedish University of Agricultural Sciences, Uppsala, Sweden.
Jazyk:	angličtina
Zdroj:	Frontiers in veterinary science [Front Vet Sci] 2021 Jun 09; Vol. 8, pp. 666219. Date of Electronic Publication: 2021 Jun 09 (Print Publication: 2021).
DOI:	10.3389/fvets.2021.666219
Abstrakt:	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·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. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Ekstrand, Pettersson, Gehring, Hedeland, Adolfsson and Lilliehöök.)
Databáze:	MEDLINE
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