Concentrations of vatinoxan and xylazine in plasma, cerebrospinal fluid and brain tissue following intravenous administration in sheep
Autor: | Ahmed G. Abu-Shahba, Bettina Mannerström, Marja Raekallio, Magdy Adam, Anna Meller, Jere Lindén, Kati Salla, Riitta Seppänen-Kaijansinkko |
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Přispěvatelé: | Production Animal Medicine, Equine and Small Animal Medicine, Veterinary Pathology and Parasitology, Veterinary Biosciences, Helsinki One Health (HOH), DAPHNE - Developing Assessment Practices in Higher Education, Teachers' Academy, Marja Raekallio / Principal Investigator, Departments of Faculty of Veterinary Medicine, Department of Oral and Maxillofacial Diseases, Clinicum, HUS Head and Neck Center, Medicum, Helsinki Institute of Life Science HiLIFE, Infra |
Rok vydání: | 2021 |
Předmět: |
Xylazine
PHARMACOKINETICS SURROGATE Pentobarbital Dose 040301 veterinary sciences Sedation medicine.medical_treatment CSF Brain tissue 413 Veterinary science DEXMEDETOMIDINE-INDUCED SEDATION cerebrospinal fluid 0403 veterinary science brain tissue 03 medical and health sciences Cerebrospinal fluid medicine Animals Saline 030304 developmental biology 2. Zero hunger 0303 health sciences Sheep General Veterinary Adult female business.industry L-659 066 MEDETOMIDINE Brain vatinoxan 04 agricultural and veterinary sciences EFFICACY Pharmaceutical Preparations Anesthesia BRADYCARDIA Administration Intravenous Female PERIPHERAL ALPHA(2)-ADRENOCEPTOR ANTAGONIST medicine.symptom business MK-467 Quinolizines medicine.drug |
Zdroj: | Veterinary Anaesthesia and Analgesia. 48:900-905 |
ISSN: | 1467-2987 |
Popis: | Objectives To investigate the extent of vatinoxan distribution into sheep brain, and whether vatinoxan influences brain concentrations of xylazine; and to examine the utility of cerebrospinal fluid (CSF) as a surrogate of brain tissue concentrations for vatinoxan and xylazine. Study design Randomised, blinded, experimental study. Animals A total of 14 adult female sheep. Methods Sheep were randomly allocated into two equal groups and premeditated with either intravenous (IV) vatinoxan (750 mu g kg(-1), VX) or saline (SX) administered 10 minutes before IV xylazine (500 mu g kg(-1)). Sedation was subjectively assessed at selected intervals before and after treatments. At 10 minutes after xylazine administration, a venous blood sample was collected and the sheep were immediately euthanised with IV pentobarbital (100 mg kg(-1)). Plasma, CSF and brain tissues were harvested, and concentrations of vatinoxan and xylazine were quantified using liquid chromatography-tandem mass spectrometry. Drug ratios were then calculated and the data were analysed as appropriate. Results The brain-to-plasma and CSF-to-plasma ratios of vatinoxan were 0.06 +/- 0.013 and 0.05 +/- 0.01 (mean +/- standard deviation), respectively. Xylazine brain concentrations were not significantly different (835 +/- 262 versus 1029 +/- 297 ng g(-1) in groups VX and SX, respectively) and were approximately 15-fold higher than those in plasma. The CSF-to-brain ratio of vatinoxan was 0.8 +/- 0.2, whereas xylazine concentrations in the brain were approximately 17-fold greater than those in CSF, with and without vatinoxan. Conclusions and clinical relevance Vatinoxan did not significantly affect sedation with xylazine or the concentrations of xylazine in the brain. CSF is not a good predictor of xylazine concentrations in the brain, whereas vatinoxan concentrations were concordant between the brain and CSF, using the dosages in this study. |
Databáze: | OpenAIRE |
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