{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T15:58:04Z","timestamp":1789660684232,"version":"4.0.1"},"reference-count":14,"publisher":"American Veterinary Medical Association (AVMA)","issue":"11","license":[{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["javma"],"published-print":{"date-parts":[[2025,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n<jats:sec>\n<jats:title>Objective<\/jats:title>\n<jats:p>To determine the frequency of the feline multidrug resistance 1 (MDR1) mutation (<jats:italic>ABCB1<\/jats:italic>1930_1931del TC) among cats experiencing macrocyclic lactone neurotoxicosis after treatment with the labeled dosage of eprinomectin- or selamectin-containing parasiticides.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>Feline patients that suffered neurological adverse effects after application of the labeled dosage of eprinomectin- or selamectin-containing parasiticide products were recruited to provide medical records and submit a DNA sample. Those with reactions highly consistent with macrocyclic lactone toxicosis were deemed cases and were compared on the basis of the macrocyclic lactone involved, outcome (survived or died), and MDR1 genotype.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>Between March 1 and December 31, 2024, 47 potential cases were identified. Twenty-seven of these met the inclusion criteria. For 26 of the 27 cases, eprinomectin was the causative macrocyclic lactone, while selamectin was the causative macrocyclic lactone for 1 case. The MDR1 genotype distribution for the 26 cases of eprinomectin-induced toxicosis was 21 of 26 (81%) homozygous for <jats:italic>ABCB1<\/jats:italic>1930_1931del TC, 4 of 26 (15%) homozygous wild type, and 1 (4%) unknown. The genotype for the selamectin-induced toxicosis case was unknown. Eprinomectin-induced neurological toxicosis resulted in death or euthanasia in 12 of 27 cases (44%; 10 homozygous for <jats:italic>ABCB1<\/jats:italic>1930_1931del TC, 1 homozygous wild type, and 1 unknown).<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Neurotoxicosis was observed in cats treated with parasiticide products containing eprinomectin and selamectin at their labeled dosage. Cats with P-glycoprotein deficiency appear to be at increased risk for eprinomectin toxicity.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Clinical Relevance<\/jats:title>\n<jats:p>Eprinomectin-containing parasiticides should not be used in cats with P-glycoprotein deficiency. A label warning is indicated to prevent additional serious and fatal adverse reactions in this identifiable subpopulation of cats.<\/jats:p>\n<\/jats:sec>","DOI":"10.2460\/javma.25.05.0304","type":"journal-article","created":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:43:24Z","timestamp":1753893804000},"page":"1414-1419","source":"Crossref","is-referenced-by-count":4,"title":["Avermectin-induced neurotoxicity and mortality reported more commonly in cats homozygous for ABCB11930_1931del TC after application of eprinomectin- versus selamectin-containing products"],"prefix":"10.2460","volume":"263","author":[{"given":"Katrina L.","family":"Mealey","sequence":"first","affiliation":[{"name":"Program in Individualized Medicine, College of Veterinary Medicine, Washington State University, Pullman, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neal S.","family":"Burke","sequence":"additional","affiliation":[{"name":"Program in Individualized Medicine, College of Veterinary Medicine, Washington State University, Pullman, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Huesser","sequence":"additional","affiliation":[{"name":"Program in Individualized Medicine, College of Veterinary Medicine, Washington State University, Pullman, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael H.","family":"Court","sequence":"additional","affiliation":[{"name":"Program in Individualized Medicine, College of Veterinary Medicine, Washington State University, Pullman, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Cline","sequence":"additional","affiliation":[{"name":"Program in Individualized Medicine, College of Veterinary Medicine, Washington State University, Pullman, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas F.","family":"Villarino","sequence":"additional","affiliation":[{"name":"Program in Individualized Medicine, College of Veterinary Medicine, Washington State University, Pullman, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1272","reference":[{"issue":"6","key":"ref1","series-title":"Curr Pharm Biotechnol","first-page":"1078","article-title":"Macrocyclic lactones in the treatment and control of parasitism in small companion animals","volume":"13","author":"Nolan TJ","year":"2012","unstructured":"Nolan TJ, Lok JB. Macrocyclic lactones in the treatment and control of parasitism in small companion animals. Curr Pharm Biotechnol. 2012;13(6):1078-1094. doi:10.2174\/138920112800399167"},{"issue":"2","key":"ref2","series-title":"Vet Clin North Am Small Anim Pract","first-page":"313","article-title":"Toxicology of avermectins and milbemycins (macrocylic lactones) and the role of P-glycoprotein in dogs and cats","volume":"42","author":"Merola VM","year":"2012","unstructured":"Merola VM, Eubig PA. Toxicology of avermectins and milbemycins (macrocylic lactones) and the role of P-glycoprotein in dogs and cats. Vet Clin North Am Small Anim Pract. 2012;42(2):313-333. doi:10.1016\/j.cvsm.2011.12.005"},{"issue":"4613","key":"ref3","series-title":"Science","first-page":"823","article-title":"Ivermectin: a potent new antiparasitic agent","volume":"221","author":"Campbell WC","year":"1983","unstructured":"Campbell WC, Fisher MH, Stapley EO, Albers-Sch\u00f6nberg G, Jacob TA. Ivermectin: a potent new antiparasitic agent. Science. 1983;221(4613):823-828. doi:10.1126\/science.6308762"},{"issue":"4","key":"ref4","series-title":"Cell","first-page":"491","article-title":"Disruption of the mouse MDR1a P-glycoprotein gene leads to a deficiency in the blood-brain barrier and to increased sensitivity to drugs","volume":"77","author":"Schinkel AH","year":"1994","unstructured":"Schinkel AH, Smit JJM, van Tellingen O,  Disruption of the mouse MDR1a P-glycoprotein gene leads to a deficiency in the blood-brain barrier and to increased sensitivity to drugs. Cell. 1994;77(4):491-502. doi:10.1016\/0092-8674(94)90212-7"},{"issue":"9","key":"ref5","series-title":"Aust Vet J","first-page":"284","article-title":"Avermectin B1 toxicity in a herd of Murray Grey cattle","volume":"64","author":"Seaman JT","year":"1987","unstructured":"Seaman JT, Eagleson JS, Carrigan MJ, Webb RF. Avermectin B1 toxicity in a herd of Murray Grey cattle. Aust Vet J. 1987;64(9):284-285. doi:10.1111\/j.1751-0813.1987.tb15963.x"},{"issue":"3","key":"ref6","series-title":"J Vet Pharmacol Ther","first-page":"226","article-title":"Application of eprinomectin-containing parasiticides at label doses causes neurological toxicosis in cats homozygous for ABCB11930_1931del TC","volume":"47","author":"Mealey KL","year":"2024","unstructured":"Mealey KL, Burke NS, Villarino NF, Court MH, Heusser JP. Application of eprinomectin-containing parasiticides at label doses causes neurological toxicosis in cats homozygous for ABCB11930_1931del TC. J Vet Pharmacol Ther. 2024;47(3):226-230. doi:10.1111\/jvp.13431"},{"issue":"8","key":"ref7","series-title":"Pharmacogenetics","first-page":"727","article-title":"Ivermectin sensitivity in Collies is associated with a deletion mutation of the MDR1 gene","volume":"11","author":"Mealey KL","year":"2001","unstructured":"Mealey KL, Bentjen SA, Gay JM, Cantor GH. Ivermectin sensitivity in Collies is associated with a deletion mutation of the MDR1 gene. Pharmacogenetics. 2001;11(8):727-733. doi:10.1097\/00008571-200111000-00012"},{"issue":"5","key":"ref8","series-title":"J Vet Pharmacol Ther","first-page":"429","article-title":"Identification of a nonsense mutation in feline ABCB1","volume":"38","author":"Mealey KL","year":"2015","unstructured":"Mealey KL, Burke NS. Identification of a nonsense mutation in feline ABCB1. J Vet Pharmacol Ther. 2015;38(5):429-433. doi:10.1111\/jvp.12212"},{"issue":"1","key":"ref9","series-title":"J Vet Pharmacol Ther","first-page":"1","article-title":"Canine and feline P-glycoprotein deficiency: what we know and where we need to go","volume":"46","author":"Mealey KL","year":"2023","unstructured":"Mealey KL, Owens JG, Freeman E. Canine and feline P-glycoprotein deficiency: what we know and where we need to go. J Vet Pharmacol Ther. 2023;46(1):1-16. doi:10.1111\/jvp.13102"},{"issue":"1","key":"ref10","series-title":"J Am Vet Med Assoc","first-page":"72","article-title":"Role of an ABCB11930_1931del TC gene mutation in a temporal cluster of macrocyclic lactone-induced neurologic toxicosis in cats associated with products labeled for companion animal use","volume":"259","author":"Mealey KL","year":"2021","unstructured":"Mealey KL, Burke NS, Connors RL. Role of an ABCB11930_1931del TC gene mutation in a temporal cluster of macrocyclic lactone-induced neurologic toxicosis in cats associated with products labeled for companion animal use. J Am Vet Med Assoc. 2021;259(1):72-76. doi:10.2460\/javma.259.1.72"},{"issue":"6","key":"ref11","series-title":"PLoS Genet","first-page":"e1009804","article-title":"Genetic epidemiology of blood type, disease and trait variants, and genome-wide genetic diversity in over 11,000 domestic cats","volume":"18","author":"Anderson H","year":"2022","unstructured":"Anderson H, Davison S, Lytle KM,  Genetic epidemiology of blood type, disease and trait variants, and genome-wide genetic diversity in over 11,000 domestic cats. PLoS Genet. 2022;18(6):e1009804. doi:10.1371\/journal.pgen.1009804"},{"issue":"10","key":"ref12","series-title":"Am J Vet Res","first-page":"1106","article-title":"Assessment of antiepileptic drugs as substrates for canine P-glycoprotein","volume":"68","author":"West CL","year":"2007","unstructured":"West CL, Mealey KL. Assessment of antiepileptic drugs as substrates for canine P-glycoprotein. Am J Vet Res. 2007;68(10):1106-1110. doi:10.2460\/ajvr.68.10.1106"},{"issue":"8","key":"ref13","series-title":"Cell Mol Life Sci","first-page":"415","article-title":"ATP-binding cassette (ABC) drug transporters in the developing blood-brain barrier: role in fetal brain protection","volume":"79","author":"Eng ME","year":"2022","unstructured":"Eng ME, Imperio GE, Bloise E, Matthews SG. ATP-binding cassette (ABC) drug transporters in the developing blood-brain barrier: role in fetal brain protection. Cell Mol Life Sci. 2022;79(8):415. doi:10.1007\/s00018-022-04432-w"},{"key":"ref14","series-title":"Parasite","first-page":"18","article-title":"Target animal safety evaluation of a novel topical combination of esafoxolaner, eprinomectin and praziquantel for cats","volume":"28","author":"Gupta A","year":"2021","unstructured":"Gupta A, Baker C, Wang H, Targa N, Pfefferkorn A, Tielemans E. Target animal safety evaluation of a novel topical combination of esafoxolaner, eprinomectin and praziquantel for cats. Parasite. 2021;28:18. doi:10.1051\/parasite\/2021015"}],"container-title":["Journal of the American Veterinary Medical Association"],"original-title":[],"link":[{"URL":"https:\/\/avmajournals.avma.org\/view\/journals\/javma\/263\/11\/javma.25.05.0304.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/avmajournals.avma.org\/downloadpdf\/journals\/javma\/263\/11\/javma.25.05.0304.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/avmajournals.avma.org\/downloadpdf\/journals\/javma\/263\/11\/javma.25.05.0304.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T16:34:12Z","timestamp":1761064452000},"score":1,"resource":{"primary":{"URL":"https:\/\/avmajournals.avma.org\/view\/journals\/javma\/263\/11\/javma.25.05.0304.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,1]]},"references-count":14,"journal-issue":{"issue":"11"},"URL":"https:\/\/doi.org\/10.2460\/javma.25.05.0304","relation":{},"ISSN":["0003-1488"],"issn-type":[{"value":"0003-1488","type":"print"}],"subject":[],"published":{"date-parts":[[2025,11,1]]}}}