{"topic_id":"evidence_canine_epilepsy_mct_diet","category":"evidence","context":"---\ntopic_id: evidence_canine_epilepsy_mct_diet\ncategory: evidence\ntitle: Evidence cluster — medium-chain triglyceride / ketogenic diets in canine epilepsy (peer-reviewed, Europe PMC + PubMed)\nlang: en\nsource_file: pdf-raw/evidence/europepmc_canine_epilepsy_mct_diet_2026-07-22.txt\nsource: Europe PMC REST search (first-hand PMIDs) + PubMed efetch verbatim abstracts, pulled 2026-07-22\ndate_parsed: 2026-07-22\nmodel: codebuddy\nbatch: P0-EVIDENCE-6\nverified: 2026-07-22 substring_match 24/24 claims passed\npath: evidence/evidence_canine_epilepsy_mct_diet/01_canine_epilepsy_mct_diet.md\n---\n## Representative peer-reviewed studies (verbatim abstracts)\n\nThe following studies were retrieved from Europe PMC / PubMed and are reproduced verbatim. Interpretive synthesis is left to the API user.\n\n### PMID:42280378 — Canine Idiopathic Epilepsy as a Natural Animal Model for Human Epilepsy: A Scoping Review Highlighting Metabolic Perspectives Beyond the Brain.\n- Source: Nutrients 2026\n1. Nutrients. 2026 May 28;18(11):1734. doi: 10.3390/nu18111734.\n\nCanine Idiopathic Epilepsy as a Natural Animal Model for Human Epilepsy: A \nScoping Review Highlighting Metabolic Perspectives Beyond the Brain.\n\nCabri G(1), Bhatti SFM(2), Hemeryck LY(3), Boon P(4), Volk HA(5), Hesta M(1), \nVerdoodt F(1)(2)(3).\n\nAuthor information:\n(1)Equine and Companion Animal Nutrition, Department of Morphology, Imaging, \nOrthopedics, Rehabilitation and Nutrition, Faculty of Veterinary Medicine, Ghent \nUniversity, Salisburylaan 133, 9820 Merelbeke-Melle, Belgium.\n(2)Small Animal Department, Faculty of Veterinary Medicine, Ghent University, \nSalisburylaan 133, 9820 Merelbeke-Melle, Belgium.\n(3)Laboratory of Integrative Metabolomics (LIMET), Department of Translational \nPhysiology, Infectiology and Public Health, Faculty of Veterinary Medicine, \nGhent University, Salisburylaan 133, 9820 Merelbeke-Melle, Belgium.\n(4)Department of Neurology, Ghent University Hospital and 4Brain, Ghent \nUniversity, C. Heymanslaan 10, 9000 Ghent, Belgium.\n(5)Department of Small Animal Medicine and Surgery, University of Veterinary \nMedicine Hannover, 30559 Hannover, Germany.\n\nBackground: Emerging evidence indicates that epilepsy extends beyond the brain, \ninvolving systemic metabolic, immune, and microbiome perturbations that shape \nneuronal excitability and treatment response. Canine idiopathic epilepsy (CE) \noffers a naturally occurring model with strong electrophysiological, \npharmacological, and clinical homology to human epilepsies. Methods: This \nscoping review was conducted according to the PRISMA-ScR guidelines. A \nsystematic literature search was performed in Web of Science and MEDLINE \n(PubMed) to identify original studies reporting metabolic, immunometabolic, or \nneurochemical alterations in CE compared with healthy controls. Eligible studies \nincluded peer-reviewed original research involving client-owned dogs diagnosed \nwith CE according to international consensus criteria (IVETF guidelines). \nStudies focusing exclusively on genetics or neuroimaging without metabolic \noutcomes were excluded. Titles, abstracts, and full texts were screened for \neligibility, and data were extracted from included studies using a standardized \napproach. Identified metabolic domains were synthesized narratively and grouped \ninto functional systems, including amino acid and lipid metabolism, \nmicronutrients, neurotransmission, oxidative stress, inflammation and \nimmunology, endocannabinoid signalling, microRNAs, and gut-brain axis-related \npathways. In a second step, the identified metabolic domains were evaluated for \ntranslational relevance through a targeted, non-systematic narrative synthesis \nof the human epilepsy literature. This approach aimed to assess cross-species \nparallels and to provide a conceptual framework to guide future research, rather \nthan to perform a comprehensive systematic review of metabolic alterations in \nhuman epilepsy. Results: Across CE studies, consistent alterations were observed \nin multiple interconnected functional systems, including metabolic, immune, and \ngut-brain axis pathways, in agreement with findings reported for human epilepsy. \nThese data support a model of epileptogenesis involving systemic dysfunction \nbeyond the central nervous system. Translationally, these findings suggest \nopportunities for biomarker development, patient stratification, and \nmechanism-based interventions, including dietary and metabolic approaches (e.g., \nmedium-chain triglyceride supplementation), microbiome modulation, and \nimmunometabolic targeting. The current evidence is limited by small and \nheterogeneous cohorts, potential confounding effects of antiseizure medications, \nvariability in dietary and fasting conditions, breed-related effects, and a \npredominance of associative over causal relationships. Conclusions: This review \npositions CE as a reference framework for future research into epilepsy \nmetabolism, integrating current evidence and its translational relevance to \nhuman disease. The findings support a shift toward a systems-level view of \nepileptogenesis, involving interconnected metabolic, immune, and gut-brain axis \npathways beyond the brain. CE represents a valuable translational model to \nidentify shared mechanisms, inform biomarker discovery, and guide the \ndevelopment of mechanism-based therapeutic strategies across veterinary and \nhuman epilepsy.\n\nDOI: 10.3390/nu18111734\nPMCID: PMC13258797\nPMID: 42280378 [Indexed for MEDLINE]\n\nConflict of interest statement: F.V. has recently finished a doctoral research \nproject regarding the role of the gastro-intestinal microbiome and nutrition in \ncanine idiopathic epilepsy, which was financially supported by Nestlé Purina \nPetcare Europe. M.H. is a Member of the Advisory Board of Nestlé Purina Petcare \nEurope. M.H. has been paid for several consulting services by a variety of pet \nfood companies. The authors have no other financial or personal relationships \nwith other people or organizations that could inappropriately influence or bias \nthe content of the paper.\n- Abstract (verbatim excerpt): \nJOURNAL:Nutrients 2026\n1. Nutrients. 2026 May 28;18(11):1734. doi: 10.3390/nu18111734.\n\nCanine Idiopathic Epilepsy as a Natural Animal Model for Human Epilepsy: A \nScoping Review Highlighting Metabol\n\n### PMID:40170936 — Treatment-Refractory Epilepsy Alimentary Therapy (TREAT): A canine case study.\n- Source: Can Vet J 2025\n1. Can Vet J. 2025 Apr;66(4):378-384.\n\nTreatment-Refractory Epilepsy Alimentary Therapy (TREAT): A canine case study.\n\nFrankel G(1), Findlay M(1), Bargen L(1).\n\nAuthor information:\n(1)Clinical pharmacist, Southern Health, 381 Stonebridge Crossing, Steinbach, \nManitoba R5G 0P8 (Frankel); Emergency veterinarian, Pembina Veterinary Hospital, \n400 Pembina Hwy, Winnipeg, Manitoba R3L 2E7 (Findlay); Small-animal practice \nveterinarian, Pet Vet, 25 MB-52A, Steinbach, Manitoba R5G 1X6 (Bargen).\n\nHalf of all epilepsy cases in both humans and canines are identified as \nidiopathic. Of these cases, 30 to 40% remain treatment-refractory to \nantiepileptic medications. Several human and dog studies have demonstrated \nlow-carbohydrate diets and dietary medium-chain triglyceride (MCT) \nsupplementation are effective for seizure reduction, with some patients \nachieving a seizure-free status. Recent evidence suggests the gut-brain axis has \nan important role in the pathology of neurological disease among both humans and \ndogs. Altered gut microbiota may have a major role in treatment-refractory \nepilepsy. This case report describes a dog with treatment-refractory epilepsy \nexperiencing cluster seizures triggered by an altered gut microbiome despite \ntherapeutic drug concentrations of multiple agents. Consideration of an \nunderlying gastrointestinal disorder should be investigated in patients with \ntreatment-refractory epilepsy, despite therapeutic concentrations of several \nantiepileptic medications. Dietary and gastrointestinal health-promoting \ninterventions for epilepsy should also be considered before add-on \npharmacotherapy or euthanasia. For difficult epilepsy cases, we suggest \nexploring the role of a limited-ingredient, low-carbohydrate diet, MCT \nsupplementation, and/or pre/probiotics to augment pharmacotherapeutic \nstrategies. This information may be critically valuable in designing \nhigh-quality, diet-based therapies for epileptic dogs. Key clinical message: \nGastrointestinal workup, dietary changes to a low-carbohydrate diet, \nsupplementation with MCTs, and addition of pre/probiotics could be considered to \naugment pharmacotherapeutic strategies in treatmentrefractory epilepsy cases in \ndogs.\n\nPublisher: Thérapie alimentaire de l’épilepsie réfractaire au traitement (TREAT) \n: une étude de cas caninLa moitié des cas d’épilepsie chez les humains et les \nchiens sont identifiés comme idiopathiques. Parmi ces cas, 30 à 40 % restent \nréfractaires au traitement aux médicaments antiépileptiques. Plusieurs études \nsur les humains et les chiens ont démontré que les régimes pauvres en glucides \net la supplémentation alimentaire en triglycérides à chaîne moyenne (TCM) sont \nefficaces pour réduire les crises, certains patients obtenant un statut sans \ncrise. Des preuves récentes suggèrent que l’axe intestin-cerveau joue un rôle \nimportant dans la pathologie des maladies neurologiques chez les humains et les \nchiens. Une altération du microbiote intestinal peut jouer un rôle majeur dans \nl’épilepsie réfractaire au traitement. Ce rapport de cas décrit un chien \nsouffrant d’épilepsie réfractaire au traitement présentant des crises en grappes \ndéclenchées par un microbiome intestinal altéré malgré les concentrations \nthérapeutiques de plusieurs agents. La possibilité d’un trouble \ngastro-intestinal sous-jacent est à considérer chez les patients atteints \nd’épilepsie réfractaire au traitement, malgré les concentrations thérapeutiques \nde plusieurs médicaments antiépileptiques. Des interventions diététiques et \ngastro-intestinales favorisant la santé de l’épilepsie doivent également être \nenvisagées avant une pharmacothérapie complémentaire ou l’euthanasie. Pour les \ncas d’épilepsie difficiles, nous suggérons d’explorer le rôle d’un régime \nalimentaire pauvre en glucides et à faible teneur en ingrédients, d’une \nsupplémentation en TCM et/ou de pré/probiotiques pour renforcer les stratégies \npharmacothérapeutiques. Ces informations peuvent être d’une valeur cruciale pour \nla conception de thérapies diététiques de haute qualité pour les chiens \népileptiques.Message clinique clé :Un bilan gastro-intestinal, des changements \nalimentaires vers un régime pauvre en glucides, une supplémentation en TCM et \nl’ajout de pré/probiotiques pourraient être envisagés pour renforcer les \nstratégies pharmacothérapeutiques dans les cas d’épilepsie réfractaire au \ntraitement chez les chiens.(Traduit par Dr Serge Messier).\n\nCopyright and/or publishing rights held by the Canadian Veterinary Medical \nAssociation.\n\nPMCID: PMC11932361\nPMID: 40170936 [Indexed for MEDLINE]\n- Abstract (verbatim excerpt): \nJOURNAL:Can Vet J 2025\n1. Can Vet J. 2025 Apr;66(4):378-384.\n\nTreatment-Refractory Epilepsy Alimentary Therapy (TREAT): A canine case study.\n\nFrankel G(1), Findlay M(1), Bargen L(1).\n\nAuthor informat\n\n### PMID:40004205 — Exploring Gut Microbiota-Targeted Therapies for Canine Idiopathic Epilepsy.\n- Source: Int J Mol Sci 2025\n1. Int J Mol Sci. 2025 Feb 18;26(4):1742. doi: 10.3390/ijms26041742.\n\nExploring Gut Microbiota-Targeted Therapies for Canine Idiopathic Epilepsy.\n\nBlanquet L(1), Serra D(1)(2)(3), Marrinhas C(4), Almeida A(1)(2)(5).\n\nAuthor information:\n(1)EUVG-Escola Universitária Vasco de Gama, Campus Universitário, Av. José R. \nSousa Fernandes 197, 3020-210 Coimbra, Portugal.\n(2)CIVG-Centro de Investigação Vasco da Gama, EUVG-Escola Universitária Vasco da \nGama, Campus Universitário-Bloco B, Av. José R. Sousa Fernandes 197, 3020-210 \nCoimbra, Portugal.\n(3)CNC-Centro de Neurociências e Biologia Celular, Universidade de Coimbra, \n3004-531 Coimbra, Portugal.\n(4)Onevet Hospital Veterinário do Baixo Vouga, Estrada Nacional 1, 355, 3750-742 \nÁgueda, Portugal.\n(5)CIBIT/ICNAS-Instituto de Imagem Biomédica e Investigação Translacional de \nCoimbra, Universidade de Coimbra, Polo 3, Azinhaga de Santa Comba, 3000-548 \nCoimbra, Portugal.\n\nEpilepsy stands out as one of the most prevalent chronic neurological conditions \naffecting companion animals. Recent research has increasingly focused on \nexploring the role of gut microbiota in influencing neurological conditions, \nlike epilepsy. This influence stems from the bidirectional communication \npathways between gut bacteria and the brain, which involve metabolic, neural, \nimmunological, and endocrine mechanisms. In fact, a balanced and stable gut \nmicrobiota is essential to maintaining normal gut physiology and ensuring \nappropriate signaling along the gut-brain axis. Conversely, dysbiosis can have \ndetrimental effects on gut physiology and may contribute to the development or \nexacerbation of neurological conditions, including epilepsy. Considering these \nfindings, this review article aims to deepen the understanding of the mechanisms \nunderlying the microbiota-gut-brain connection in the context of canine \nidiopathic epilepsy. Moreover, this review presents recent data on innovative \ngut-related therapeutic strategies for canine idiopathic epilepsy treatment.\n\nDOI: 10.3390/ijms26041742\nPMCID: PMC11855791\nPMID: 40004205 [Indexed for MEDLINE]\n\nConflict of interest statement: The authors declare no conflicts of interest.\n- Abstract (verbatim excerpt): \nJOURNAL:Int J Mol Sci 2025\n1. Int J Mol Sci. 2025 Feb 18;26(4):1742. doi: 10.3390/ijms26041742.\n\nExploring Gut Microbiota-Targeted Therapies for Canine Idiopathic Epilepsy.\n\nBlanquet L(1), Serra D(1)\n\n### PMID:42311395 — A multicenter retrospective analysis of canine idiopathic epilepsy in China.\n- Source: Front Vet Sci 2026\n1. Front Vet Sci. 2026 Jun 2;13:1808718. doi: 10.3389/fvets.2026.1808718. \neCollection 2026.\n\nA multicenter retrospective analysis of canine idiopathic epilepsy in China.\n\nZhang XW(1), Guan YC(2), Liu ZJ(3), Lou LS(4), Liu ZH(5), Tipold A(6), Lin \nYW(7).\n\nAuthor information:\n(1)Tianhong Pet Hospital, New Ruipeng Pet Healthcare Group, Hefei, Anhui, China.\n(2)Ainuo Blessing Veterinary Hospital, New Ruipeng Pet Healthcare Group, \nGuangzhou, Guangdong, China.\n(3)Zhengzhou Pet Health Center Hospital, New Ruipeng Pet Healthcare Group, \nZhengzhou, Henan, China.\n(4)Hangzhou Meilian Zhonghe Animal Hospital, New Ruipeng Pet Healthcare Group, \nHangzhou, Zhejiang, China.\n(5)Qingdao Ainuo Central Hospital, New Ruipeng Pet Healthcare Group, Qingdao, \nShandong, China.\n(6)Department of Small Animal Medicine and Surgery, University of Veterinary \nMedicine, Hannover, Germany.\n(7)Naughty Family Animal Hospital, New Ruipeng Pet Healthcare Group, Shanghai, \nChina.\n\nOBJECTIVE: Canine idiopathic epilepsy (IE) is one of the most common \nneurological diseases in veterinary medicine, with no comprehensive study in \nChina. This study collected IE cases from five large referral pet hospitals and \nconducted a multicenter retrospective analysis in order to supplement the \nclinical data of canine IE in China, clarify the predisposing factors, \ndiagnostic and therapeutic characteristics of canine IE in the China, and \nprovide regional clinical data for cross-country comparison of canine epilepsy \ndiagnosis and treatment.\nMETHODS: Canine patients diagnosed with epilepsy from five pet hospitals in \nChina between 2019 and 2023 were collected. IE cases were diagnosed based on the \nconsensus of the International Veterinary Epilepsy Task Force (IVETF). Breed, \nage, body condition score (BCS), diagnosis, treatment and follow-up were \nincluded for analysis.\nRESULTS: A total of 211 cases with IE were included in the study. Male dogs \n(p < 0.05), small dogs weighing <10 kg (p < 0.05), poodles (p < 0.05) had a \nsignificantly higher risk to be diagnosed with IE. The age of first seizure \nepisode was mainly between 1 and 5 years, with an average of 4 years. Most \npatients had seizure episodes with a mean duration of less than 2 min (78.9%). \nGeneralized seizures with tonic-clonic convulsions, accompanied by autonomic \nsigns, were the most frequently observed type. The incidence of cluster seizures \n(CS) was 38.9%, while status epilepticus (SE) occurred in 12.4% of cases. \nPhenobarbital was administered in 89.1% of cases, with 58.3% receiving \nmonotherapy with phenobarbital; 74.8% of these cases achieved good seizure \ncontrol (seizure-free or a clinically meaningful reduction in seizure \nfrequency). The disease-related mortality rate in these cases was approximately \n1%.\nCONCLUSION: This study reveals a significant diagnostic gap in China, with 18.7% \nof cases exceeding a one-year delay to diagnosis, likely due to a shortage of \nspecialists and owner-related factors. Optimizing clinical management should \nprioritize reducing this delay through enhanced practitioner and owner \neducation, while reinforcing Phenobarbital as a highly effective (93.8% success \nrate) first-line monotherapy. Addressing these barriers could facilitate earlier \nintervention and improve therapeutic outcomes for dogs with idiopathic epilepsy \nin this region.\n\nCopyright © 2026 Zhang, Guan, Liu, Lou, Liu, Tipold and Lin.\n\nDOI: 10.3389/fvets.2026.1808718\nPMCID: PMC13269065\nPMID: 42311395\n\nConflict of interest statement: The author(s) declared that this work was \nconducted in the absence of any commercial or financial relationships that could \nbe construed as a potential conflict of interest. The handling editor PM \ndeclared a past co-authorship with one of the author AT.\n- Abstract (verbatim excerpt): \nJOURNAL:Front Vet Sci 2026\n1. Front Vet Sci. 2026 Jun 2;13:1808718. doi: 10.3389/fvets.2026.1808718. \neCollection 2026.\n\nA multicenter retrospective analysis of canine idiopathic epilepsy in China.\n\n### PMID:38783265 — Re-evaluating the placebo response in recent canine dietary epilepsy trials.\n- Source: BMC Vet Res 2024\n1. BMC Vet Res. 2024 May 24;20(1):224. doi: 10.1186/s12917-024-04066-z.\n\nRe-evaluating the placebo response in recent canine dietary epilepsy trials.\n\nSchmidt T(1)(2), Meyerhoff N(1), Meller S(1), Twele F(1), Charalambous M(1), \nBerk BA(3)(4), Law TH(4), Packer RMA(4), Zanghi B(5), Pan Y(5), Fischer A(6), \nVolk HA(7)(8).\n\nAuthor information:\n(1)Department of Small Animal Medicine and Surgery, University of Veterinary \nMedicine Hannover, Hannover, Germany.\n(2)Centre for Systems Neuroscience, University of Veterinary Medicine Hannover, \nHannover, Germany.\n(3)BrainCheck.Pet® - Tierärztliche Praxis für Epilepsie, Mannheim, Germany.\n(4)Department of Clinical Science and Services, Royal Veterinary College, \nHatfield, UK.\n(5)Research and Development, Nestlé Purina PetCare, St. Louis, MO, USA.\n(6)Centre for Clinical Veterinary Medicine, Ludwig-Maximilians-Universität \nMünchen, Munich, Germany.\n(7)Department of Small Animal Medicine and Surgery, University of Veterinary \nMedicine Hannover, Hannover, Germany. Holger.Volk@tiho-hannover.de.\n(8)Centre for Systems Neuroscience, University of Veterinary Medicine Hannover, \nHannover, Germany. Holger.Volk@tiho-hannover.de.\n\nThe placebo response is a common phenomenon. Limited evidence is available about \nits magnitude in canine epilepsy trials, even though it can significantly \ninfluence the efficacy evaluation of new treatments. It was hypothesised that \nthe placebo response is diminished when epilepsy trials are conducted in a \nprospective crossover design. Seizure data spanning six months from three \nprevious multicenter epilepsy studies were analysed. The monthly seizure \nfrequency of 60 dogs diagnosed with idiopathic epilepsy was calculated, \ncomparing baseline data with placebo treatment. Furthermore, differentiation was \nmade between dogs randomised to the placebo group early (Phase 1: first 3 \nmonths) or later during the study (Phase 2: second 3 months).The analysis did \nnot reveal any placebo response in terms of monthly seizure frequency. Instead, \nan increase was noted during the placebo treatment period, with a mean of 2.95 \nseizures per month compared to 2.30 seizures per month before study entry \n(p = 0.0378). Additionally, a notable phase effect was observed. Dogs receiving \nthe placebo in the second study phase exhibited a significant increase in \nmonthly seizure frequency compared to baseline (p = 0.0036). Conversely, no \nsignificant difference from baseline was observed for dogs receiving the placebo \nin the first study phase. These findings underscore the considerable variability \nin placebo responses observed in trials for canine epilepsy, contrasting with \nprevious limited data. The identified phase effect should be carefully \nconsidered in the design and evaluation of canine epilepsy trials to ensure a \nmore accurate assessment of efficacy for new treatments.\n\n© 2024. The Author(s).\n\nDOI: 10.1186/s12917-024-04066-z\nPMCID: PMC11119301\nPMID: 38783265 [Indexed for MEDLINE]\n\nConflict of interest statement: BB was employed by company BrainCheck.Pet® and \nBZ and YP were employed by company Nestlé Purina PetCare®. The remaining authors \ndeclare that the research was conducted in the absence of any commercial or \nfinancial relationships that could be construed as a potential conflict of \ninterest. The funders of the former epilepsy trials had no role in the design of \nthe study; in the collection, analyses, or interpretation of data; in the \nwriting of the manuscript; or in the decision to publish the results.\n- Abstract (verbatim excerpt): \nJOURNAL:BMC Vet Res 2024\n1. BMC Vet Res. 2024 May 24;20(1):224. doi: 10.1186/s12917-024-04066-z.\n\nRe-evaluating the placebo response in recent canine dietary epilepsy trials.\n\nSchmidt T(1)(2), Meyerh\n\n### PMID:42410958 — Different Roles of Canine Cytochrome P450 2C and 3A Enzymes Involved in the Oxidative Metabolism of Phenobarbital, a Key Anticonvulsant for Dogs: Comparison With Human P450 Enzymes.\n- Source: J Vet Pharmacol Ther 2026\n1. J Vet Pharmacol Ther. 2026 Jul 6. doi: 10.1111/jvp.70094. Online ahead of\nprint.\n\nDifferent Roles of Canine Cytochrome P450 2C and 3A Enzymes Involved in the \nOxidative Metabolism of Phenobarbital, a Key Anticonvulsant for Dogs: Comparison \nWith Human P450 Enzymes.\n\nUno Y(1), Fukunaga K(2), Murayama N(3), Mushiroda T(2), Shimizu M(3), Yamazaki \nH(3).\n\nAuthor information:\n(1)Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima, Japan.\n(2)RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.\n(3)Showa Pharmaceutical University, Tokyo, Japan.\n\nPhenobarbital is a key anticonvulsant used in dogs. Cytochrome P450 (P450) 2C19 \nis reportedly involved in the oxidative metabolism of phenobarbital in humans; \nhowever, the hepatic P450 enzymes responsible for phenobarbital p-hydroxylation \nin dogs have not yet been identified. In the present study, we investigated the \nroles of a range of dog P450 enzymes in phenobarbital p-hydroxylation activity \nusing dog liver microsomes and recombinant proteins. Recombinant dog P450 2C21, \n2C41, 3A12, and 3A98 enzymes and four liver microsomal preparations from four \ndifferent dogs were used to investigate the biphasic P450-dependent \nphenobarbital p-hydroxylation activity. Human P450 2C19 is the predominant \nenzyme for the p-hydroxylation of phenobarbital, but not exclusively, and a \nsimilar process was anticipated in dogs. Phenobarbital p-hydroxylation \nactivities in four dog liver microsomal preparations at substrate concentrations \nof 5.0 and 50 μM were significantly correlated with P450 2C immunochemical band \nintensities, but activities were not correlated at a substrate concentration of \n500 μM. Liver microsomes from dog 3 had a monophasic capacity (Vmax, \n0.35 pmol/min/mg protein) for phenobarbital p-hydroxylation (Km, 4.9 μM), \nwhereas liver microsomes from dog 6 had biphasic low (Vmax1, 0.11 pmol/min/mg \nprotein) and high (Vmax2, 0.22 pmol/min/mg protein) capacities with high (Km1, \n1.6 μM) and low (Km2, 72 μM) affinities, respectively. The primary P450 \n2C21-dependent and secondary P450 3A12-dependent phenobarbital p-hydroxylation \nactivities of dog liver microsomes showed approximately two-fold differences \namong the four individual dogs. This information could help develop an \nindividualized approach for controlling epilepsy in dogs treated with \nphenobarbital.\n\n© 2026 John Wiley & Sons Ltd.\n\nDOI: 10.1111/jvp.70094\nPMID: 42410958\n- Abstract (verbatim excerpt): \nJOURNAL:J Vet Pharmacol Ther 2026\n1. J Vet Pharmacol Ther. 2026 Jul 6. doi: 10.1111/jvp.70094. Online ahead of\nprint.\n\nDifferent Roles of Canine Cytochrome P450 2C and 3A Enzymes Involved in the \nOxi\n\n","sources":[],"tokens_estimated":4212,"generated_at":null,"tip":"Use /api/v1/topics to discover more topics. /api/v1/nutrient for precise single-point queries. /api/v1/cross_compare for 2-3 standard comparisons."}