Tyler S Nelson, Heather N Allen, April Hardison, Erin Miscioscia, Rajesh Khanna, Elizabeth A Maxwell
{"title":"病例报告:ABCB1-1∆(MDR1)突变的柯利纯合子对丁托啡诺的不良反应。","authors":"Tyler S Nelson, Heather N Allen, April Hardison, Erin Miscioscia, Rajesh Khanna, Elizabeth A Maxwell","doi":"10.3389/fvets.2025.1603375","DOIUrl":null,"url":null,"abstract":"<p><p>Certain dog breeds, particularly herding breeds like Collies, are predisposed to drug sensitivity due to the <i>ABCB1-1∆</i> (previously known as <i>MDR1</i>) mutation, which disrupts P-glycoprotein (P-gp) function. This mutation impairs drug efflux at the blood-brain barrier, leading to increased susceptibility to neurotoxic effects. While adverse reactions to P-gp substrate drugs such as macrocyclic lactones and chemotherapeutics are well documented, opioid sensitivity remains poorly understood. This case report documents a Collie that developed severe neurotoxicity, including profound sedation, ataxia, hypersalivation, and seizures, following a single 0.2 mg/kg dose of butorphanol. Symptoms persisted despite supportive care, requiring continuous naloxone administration for approximately 40 h before significant improvement. Neurotoxicological effects may have been exacerbated by metoclopramide and maropitant, known P-gp substrates. This case underscores the need for further research into opioid pharmacokinetics in <i>ABCB1-1∆</i> mutant dogs and highlights the importance of genetic screening in veterinary practice. To enhance patient safety, integration of automated alerts within electronic medical record systems is recommended to flag high-risk drugs for at-risk breeds, providing real-time warnings, dosing adjustments, and monitoring guidance. These measures could reduce adverse drug reactions and improve clinical outcomes in genetically susceptible dogs.</p>","PeriodicalId":12772,"journal":{"name":"Frontiers in Veterinary Science","volume":"12 ","pages":"1603375"},"PeriodicalIF":2.6000,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12159028/pdf/","citationCount":"0","resultStr":"{\"title\":\"Case Report: Adverse reaction to butorphanol in a Collie homozygous for the <i>ABCB1-1∆</i> (<i>MDR1</i>) mutation.\",\"authors\":\"Tyler S Nelson, Heather N Allen, April Hardison, Erin Miscioscia, Rajesh Khanna, Elizabeth A Maxwell\",\"doi\":\"10.3389/fvets.2025.1603375\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Certain dog breeds, particularly herding breeds like Collies, are predisposed to drug sensitivity due to the <i>ABCB1-1∆</i> (previously known as <i>MDR1</i>) mutation, which disrupts P-glycoprotein (P-gp) function. This mutation impairs drug efflux at the blood-brain barrier, leading to increased susceptibility to neurotoxic effects. While adverse reactions to P-gp substrate drugs such as macrocyclic lactones and chemotherapeutics are well documented, opioid sensitivity remains poorly understood. This case report documents a Collie that developed severe neurotoxicity, including profound sedation, ataxia, hypersalivation, and seizures, following a single 0.2 mg/kg dose of butorphanol. Symptoms persisted despite supportive care, requiring continuous naloxone administration for approximately 40 h before significant improvement. Neurotoxicological effects may have been exacerbated by metoclopramide and maropitant, known P-gp substrates. This case underscores the need for further research into opioid pharmacokinetics in <i>ABCB1-1∆</i> mutant dogs and highlights the importance of genetic screening in veterinary practice. 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Case Report: Adverse reaction to butorphanol in a Collie homozygous for the ABCB1-1∆ (MDR1) mutation.
Certain dog breeds, particularly herding breeds like Collies, are predisposed to drug sensitivity due to the ABCB1-1∆ (previously known as MDR1) mutation, which disrupts P-glycoprotein (P-gp) function. This mutation impairs drug efflux at the blood-brain barrier, leading to increased susceptibility to neurotoxic effects. While adverse reactions to P-gp substrate drugs such as macrocyclic lactones and chemotherapeutics are well documented, opioid sensitivity remains poorly understood. This case report documents a Collie that developed severe neurotoxicity, including profound sedation, ataxia, hypersalivation, and seizures, following a single 0.2 mg/kg dose of butorphanol. Symptoms persisted despite supportive care, requiring continuous naloxone administration for approximately 40 h before significant improvement. Neurotoxicological effects may have been exacerbated by metoclopramide and maropitant, known P-gp substrates. This case underscores the need for further research into opioid pharmacokinetics in ABCB1-1∆ mutant dogs and highlights the importance of genetic screening in veterinary practice. To enhance patient safety, integration of automated alerts within electronic medical record systems is recommended to flag high-risk drugs for at-risk breeds, providing real-time warnings, dosing adjustments, and monitoring guidance. These measures could reduce adverse drug reactions and improve clinical outcomes in genetically susceptible dogs.
期刊介绍:
Frontiers in Veterinary Science is a global, peer-reviewed, Open Access journal that bridges animal and human health, brings a comparative approach to medical and surgical challenges, and advances innovative biotechnology and therapy.
Veterinary research today is interdisciplinary, collaborative, and socially relevant, transforming how we understand and investigate animal health and disease. Fundamental research in emerging infectious diseases, predictive genomics, stem cell therapy, and translational modelling is grounded within the integrative social context of public and environmental health, wildlife conservation, novel biomarkers, societal well-being, and cutting-edge clinical practice and specialization. Frontiers in Veterinary Science brings a 21st-century approach—networked, collaborative, and Open Access—to communicate this progress and innovation to both the specialist and to the wider audience of readers in the field.
Frontiers in Veterinary Science publishes articles on outstanding discoveries across a wide spectrum of translational, foundational, and clinical research. The journal''s mission is to bring all relevant veterinary sciences together on a single platform with the goal of improving animal and human health.