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Metabolomics. 2021 Jun 02;17(6):54. doi: 10.1007/s11306-021-01803-5.

Serum NMR metabolomics uncovers multiple metabolic changes in phenobarbital-treated dogs.

Metabolomics : Official journal of the Metabolomic Society

Claudia Ottka, Corinna Weber, Elisabeth Müller, Hannes Lohi

Affiliations

  1. PetBiomics Ltd., Helsinki, Finland. [email protected].
  2. Department of Veterinary Biosciences, University of Helsinki, Helsinki, Finland. [email protected].
  3. Department of Medical and Clinical Genetics, University of Helsinki, Helsinki, Finland. [email protected].
  4. Folkhälsan Research Center, Helsinki, Finland. [email protected].
  5. LABOKLIN GmbH & Co KG, Bad Kissingen, Germany.
  6. PetBiomics Ltd., Helsinki, Finland.
  7. Department of Veterinary Biosciences, University of Helsinki, Helsinki, Finland.
  8. Department of Medical and Clinical Genetics, University of Helsinki, Helsinki, Finland.
  9. Folkhälsan Research Center, Helsinki, Finland.

PMID: 34076758 PMCID: PMC8172515 DOI: 10.1007/s11306-021-01803-5

Abstract

INTRODUCTION: Phenobarbital is a commonly used anticonvulsant for the treatment of canine epileptic seizures. In addition to its central nervous system (CNS) depressing effects, long-term phenobarbital administration affects liver function. However, broader metabolic consequences of phenobarbital treatment are poorly characterized.

OBJECTIVES: To identify metabolic changes in the sera of phenobarbital-treated dogs and to investigate the relationship between serum phenobarbital concentration and metabolite levels.

METHODS: Leftovers of clinical samples were used: 58 cases with phenobarbital concentrations ranging from 7.8 µg/mL to 50.8 µg/mL, and 25 controls. The study design was cross-sectional. The samples were analyzed by a canine-specific

RESULTS: Increasing concentrations of glycoprotein acetyls, LDL particle size, palmitic acid, and saturated fatty acids, and decreasing concentrations of albumin, glutamine, histidine, LDL particle concentration, multiple HDL measures, and polyunsaturated fatty acids increased the odds of the sample belonging to the phenobarbital-treated group, having a p-value < .0033, and area under the curve (AUC) > .7. Albumin and glycoprotein acetyls had the best discriminative ability between the groups (AUC: .94). No linear associations between phenobarbital and metabolite concentrations were observed.

CONCLUSION: The identified metabolites are known to associate with, for example, liver and CNS function, inflammatory processes and drug binding. The lack of a linear association to phenobarbital concentration suggests that other factors than the blood phenobarbital concentration contribute to the magnitude of metabolic changes.

Keywords: Anticonvulsant; Canine; Epilepsy; Metabolism; Phenobarbital

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