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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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>To identify metabolic changes in the sera of phenobarbital-treated dogs and to investigate the relationship between serum phenobarbital concentration and metabolite levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Leftovers of clinical samples were used: 58 cases with phenobarbital concentrations ranging from 7.8\u00a0\u00b5g\/mL to 50.8\u00a0\u00b5g\/mL, and 25 controls. The study design was cross-sectional. The samples were analyzed by a canine-specific<jats:sup>1<\/jats:sup>H NMR metabolomics platform. Differences between the case and control groups were evaluated by logistic regression. The linear relationship between metabolite and phenobarbital concentrations was evaluated using linear regression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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<jats:italic>p<\/jats:italic>-value\u2009&lt;\u2009.0033, and area under the curve (AUC)\u2009&gt;\u2009.7. Albumin and glycoprotein acetyls had the best discriminative ability between the groups (AUC: .94). No linear associations between phenobarbital and metabolite concentrations were observed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.1007\/s11306-021-01803-5","type":"journal-article","created":{"date-parts":[[2021,6,2]],"date-time":"2021-06-02T14:23:30Z","timestamp":1622643810000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Serum NMR metabolomics uncovers multiple metabolic changes in phenobarbital-treated dogs"],"prefix":"10.1007","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4837-6309","authenticated-orcid":false,"given":"Claudia","family":"Ottka","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinna","family":"Weber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"M\u00fcller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannes","family":"Lohi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,6,2]]},"reference":[{"key":"1803_CR1","doi-asserted-by":"publisher","first-page":"175","DOI":"10.3233\/JPN-2010-0398","volume":"8","author":"HA Al Khayat","year":"2010","unstructured":"Al Khayat, H. 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Elisabeth M\u00fcller is the managing director and Corinna Weber the head of department of LABOKLIN \u2013 an animal diagnostic laboratory.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"All used samples were leftovers of clinical samples, collected for the benefit of the patient.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Consent for the scientific use of leftover canine sample material was obtained for all samples during sample submission.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"The study does not include any personal data or photographs of human subjects.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}}],"article-number":"54"}}