{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T08:28:59Z","timestamp":1773908939656,"version":"3.50.1"},"reference-count":32,"publisher":"American Veterinary Medical Association (AVMA)","issue":"7","license":[{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"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":["ajvr"],"published-print":{"date-parts":[[2025,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n<jats:sec id=\"sc_a1\">\n<jats:title>Objective<\/jats:title>\n<jats:p>To evaluate the pharmacokinetics of emodepside in dogs following single-dose administration of the FDA-approved feline topical solution orally and topically and the European Medicines Agency\u2013approved canine modified-release tablet orally and to assess the bioequivalence of the feline topical solution administered orally compared to the canine modified-release tablet.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sc_a2\">\n<jats:title>Methods<\/jats:title>\n<jats:p>This study was conducted in 3 phases, during which dogs received single doses of emodepside as the feline topical solution (1 mg\/kg) orally, the canine modified-release tablet (1 mg\/kg) orally, and the topical feline solution (3 mg\/kg) topically. Plasma pharmacokinetic profiles were determined for 21 days postdose. Bioequivalence testing was conducted for orally administered emodepside.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sc_a3\">\n<jats:title>Results<\/jats:title>\n<jats:p>7 healthy client-owned dogs (4 female and 3 male) were prospectively enrolled in this crossover study from May through August 2023. Oral administration of the feline topical solution resulted in markedly greater emodepside absorption than the modified-release tablet and was not bioequivalent. Emodepside plasma concentrations following topical administration of the FDA formulation were 36- to 122-fold lower than after oral administration.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sc_a4\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>The feline topical solution administered orally at 1 mg\/kg is not bioequivalent to the canine modified-release tablet. Markedly higher absorption of the feline topical solution administered orally raises potential safety concerns for extralabel use in dogs to treat multianthelmintic drug-resistant hookworm infections. Poor absorption following topical administration suggests it may be unsuitable for treating multianthelmintic drug-resistant hookworm infections.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sc_a5\">\n<jats:title>Clinical Relevance<\/jats:title>\n<jats:p>These findings highlight potential emodepside toxicity risks with extralabel use of the FDA-approved topical feline product and help inform safe off-label use in dogs.<\/jats:p>\n<\/jats:sec>","DOI":"10.2460\/ajvr.25.01.0027","type":"journal-article","created":{"date-parts":[[2025,4,4]],"date-time":"2025-04-04T18:25:25Z","timestamp":1743791125000},"source":"Crossref","is-referenced-by-count":2,"title":["Topical and oral emodepside formulations for last-line treatment of multianthelmintic drug-resistant hookworms when given orally to dogs are not bioequivalent"],"prefix":"10.2460","volume":"86","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1266-3349","authenticated-orcid":true,"given":"Theresa A.","family":"Quintana","sequence":"first","affiliation":[{"name":"Department of Diagnostic Medicine and Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS"},{"name":"Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Greta N.","family":"Karwath","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erin J.","family":"Mayhue","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Medicine and Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6963-7646","authenticated-orcid":true,"given":"Maria C.","family":"Jugan","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, College of Veterinary Medicine, Kansas State University, Manhattan, KS"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3077-0201","authenticated-orcid":true,"given":"Jeba R. J.","family":"Jesudoss Chelladurai","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Medicine and Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS"},{"name":"Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8430-4973","authenticated-orcid":true,"given":"Stephanie E.","family":"Martinez","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS"},{"name":"Department of Veterinary Clinical and Life Sciences, College of Veterinary Medicine, Utah State University, Logan, UT"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1272","reference":[{"issue":"6","key":"B1","series-title":"Parasitol Res","first-page":"481","article-title":"Cyclooctadepsipeptides\u2014a new class of anthelmintically active compounds","volume":"88","author":"Harder A","year":"2002","unstructured":"Harder A, von Samson-Himmelstjerna G. Cyclooctadepsipeptides\u2014a new class of anthelmintically active compounds. Parasitol Res. 2002;88(6):481\u2013488. doi:10.1007\/s00436-002-0619-2"},{"issue":"9","key":"B2","series-title":"Trends Parasitol","first-page":"385","article-title":"Anthelmintic cyclooctadepsipeptides: complex in structure and mode of action","volume":"28","author":"Kr\u00fccken J","year":"2012","unstructured":"Kr\u00fccken J, Harder A, Jeschke P, et al. Anthelmintic cyclooctadepsipeptides: complex in structure and mode of action. Trends Parasitol. 2012;28(9):385\u2013394. doi:10.1016\/j.pt.2012.06.005"},{"issue":"5","key":"B3","series-title":"J Antibiot (Tokyo)","first-page":"692","article-title":"A new anthelmintic cyclodepsipeptide, PF1022A","volume":"45","author":"Sasaki T","year":"1992","unstructured":"Sasaki T, Takagi M, Yaguchi T, Miyadoh S, Okada T, Koyama M. A new anthelmintic cyclodepsipeptide, PF1022A. J Antibiot (Tokyo). 1992;45(5):692\u2013697. doi:10.7164\/antibiotics.45.692"},{"issue":"7","key":"B4","series-title":"FASEB J","first-page":"1332","article-title":"Latrophilin-like receptor from the parasitic nematode Haemonchus contortus as target for the anthelmintic depsipeptide PF1022A","volume":"15","author":"Saeger B","year":"2001","unstructured":"Saeger B, Schmitt-Wrede HP, Dehnhardt M, et al. Latrophilin-like receptor from the parasitic nematode Haemonchus contortus as target for the anthelmintic depsipeptide PF1022A. FASEB J. 2001;15(7):1332\u20131334. doi:10.1096\/fj.00-0664fje"},{"issue":"pt 1","key":"B5","series-title":"Parasitology","first-page":"79","article-title":"The effect of the anthelmintic emodepside at the neuromuscular junction of the parasitic nematode Ascaris suum","volume":"126","author":"Willson J","year":"2003","unstructured":"Willson J, Amliwala K, Harder A, et al. The effect of the anthelmintic emodepside at the neuromuscular junction of the parasitic nematode Ascaris suum. Parasitology. 2003;126(pt 1):79\u201386. doi:10.1017\/S0031182002002639"},{"issue":"14","key":"B6","series-title":"Int J Parasitol","first-page":"1577","article-title":"The calcium-activated potassium channel, SLO-1, is required for the action of the novel cyclo-octadepsipeptide anthelmintic, emodepside, in Caenorhabditis elegans","volume":"37","author":"Guest M","year":"2007","unstructured":"Guest M, Bull K, Walker RJ, et al. The calcium-activated potassium channel, SLO-1, is required for the action of the novel cyclo-octadepsipeptide anthelmintic, emodepside, in Caenorhabditis elegans. Int J Parasitol. 2007;37(14):1577\u20131588. doi:10.1016\/j.ijpara.2007.05.006"},{"issue":"4","key":"B7","series-title":"Invert Neurosci","first-page":"199","article-title":"SLO, SLO, quick, quick, slow: calcium-activated potassium channels as regulators of Caenorhabditis elegans behaviour and targets for anthelmintics","volume":"7","author":"Holden-Dye L","year":"2007","unstructured":"Holden-Dye L, O\u2019Connor V, Hopper NA, et al. SLO, SLO, quick, quick, slow: calcium-activated potassium channels as regulators of Caenorhabditis elegans behaviour and targets for anthelmintics. Invert Neurosci. 2007;7(4):199\u2013208. doi:10.1007\/s10158-007-0057-z"},{"key":"B8","year":"2007","unstructured":"Freedom of information summary for NADA 141-275, Profender. FDA. 2007. Accessed August 25, 2024. https:\/\/animaldrugsatfda.fda.gov\/adafda\/app\/search\/public\/document\/downloadFoi\/834"},{"key":"B9","year":"2008","unstructured":"Summary of product characteristics: Profender. European Medicines Agency. 2008. Accessed September 3, 2024. https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/profender-epar-product-information_en.pdf"},{"key":"B10","year":"2011","unstructured":"Summary of product characteristics: Procox. European Medicines Agency. 2011. Accessed September 3, 2024. https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/procox-epar-product-information_en.pdf"},{"issue":"7","key":"B11","series-title":"PLoS Pathog","first-page":"e1009682","article-title":"Development of emodepside as a possible adulticidal treatment for human onchocerciasis\u2014the fruit of a successful industrial\u2013academic collaboration","volume":"17","author":"Kr\u00fccken J","year":"2021","unstructured":"Kr\u00fccken J, Holden-Dye L, Keiser J, et al. Development of emodepside as a possible adulticidal treatment for human onchocerciasis\u2014the fruit of a successful industrial\u2013academic collaboration. PLoS Pathog. 2021;17(7):e1009682. doi:10.1371\/journal.ppat.1009682"},{"issue":"1","key":"B12","series-title":"Parasit Vectors","first-page":"576","article-title":"Multiple drug resistance in the canine hookworm Ancylostoma caninum: an emerging threat?","volume":"12","author":"Jimenez Castro PD","year":"2019","unstructured":"Jimenez Castro PD, Howell SB, Schaefer JJ, Avramenko RW, Gilleard JS, Kaplan RM. Multiple drug resistance in the canine hookworm Ancylostoma caninum: an emerging threat? Parasit Vectors. 2019;12(1):576. doi:10.1186\/s13071-019-3828-6"},{"key":"B13","series-title":"Int J Parasitol Drugs Drug Resist","first-page":"27","article-title":"Evaluation of the in vitro susceptibility of various filarial nematodes to emodepside","volume":"17","author":"H\u00fcbner MP","year":"2021","unstructured":"H\u00fcbner MP, Townson S, Gokool S, et al. Evaluation of the in vitro susceptibility of various filarial nematodes to emodepside. Int J Parasitol Drugs Drug Resist. 2021;17:27\u201335. doi:10.1016\/j.ijpddr.2021.07.005"},{"issue":"1","key":"B14","series-title":"Parasit Vectors","first-page":"226","article-title":"Evaluation of emodepside in laboratory models of human intestinal nematode and schistosome infections","volume":"12","author":"Karpstein T","year":"2019","unstructured":"Karpstein T, Pasche V, H\u00e4berli C, Scandale I, Neodo A, Keiser J. Evaluation of emodepside in laboratory models of human intestinal nematode and schistosome infections. Parasit Vectors. 2019;12(1):226. doi:10.1186\/s13071-019-3476-x"},{"key":"B15","series-title":"Int J Parasitol Drugs Drug Resist","first-page":"22","article-title":"Efficacy evaluation of anthelmintic products against an infection with the canine hookworm (Ancylostoma caninum) isolate Worthy 4.1 F3P in dogs","volume":"13","author":"Jimenez Castro PD","year":"2020","unstructured":"Jimenez Castro PD, Mansour A, Charles S, et al. Efficacy evaluation of anthelmintic products against an infection with the canine hookworm (Ancylostoma caninum) isolate Worthy 4.1 F3P in dogs. Int J Parasitol Drugs Drug Resist. 2020;13:22\u201327. doi:10.1016\/j.ijpddr.2020.04.003"},{"key":"B16","series-title":"Clin Brief","first-page":"61","article-title":"Persistent or suspected-resistant hookworm infections","volume":"8","author":"Jimenez Castro PD","year":"2020","unstructured":"Jimenez Castro PD, Kaplan RM. Persistent or suspected-resistant hookworm infections. Clin Brief. 2020;8:61\u201368."},{"key":"B17","year":"2016","unstructured":"CVM guidance for industry #224 (VICH GL52) bioequivalence: blood level bioequivalence study. FDA. 2016. Accessed October 4, 2024. https:\/\/www.fda.gov\/media\/89840\/download"},{"issue":"1","key":"B18","series-title":"J Vet Pharmacol Ther","first-page":"74","article-title":"Brain penetration of emodepside is increased in P-glycoprotein-deficient mice and leads to neurotoxicosis","volume":"38","author":"Elmsh\u00e4user S","year":"2015","unstructured":"Elmsh\u00e4user S, Straehle LC, Kranz J, Krebber R, Geyer J. Brain penetration of emodepside is increased in P-glycoprotein-deficient mice and leads to neurotoxicosis. J Vet Pharmacol Ther. 2015;38(1):74\u201379. doi:10.1111\/jvp.12149"},{"key":"B19","series-title":"Curr Res Parasitol Vector Borne Dis","first-page":"100126","article-title":"Plasma pharmacokinetics of tigolaner, emodepside, and praziquantel following topical administration of a combination product (Felpreva) and of intravenous administration of the individual active ingredients in cats","volume":"4","author":"Mencke N","year":"2023","unstructured":"Mencke N, B\u00e4umer W, Fraatz K, Krebber R, Schneider M, Blazejak K. Plasma pharmacokinetics of tigolaner, emodepside, and praziquantel following topical administration of a combination product (Felpreva) and of intravenous administration of the individual active ingredients in cats. Curr Res Parasitol Vector Borne Dis. 2023;4:100126. doi:10.1016\/j.crpvbd.2023.100126"},{"issue":"2","key":"B20","series-title":"J Am Anim Hosp Assoc","first-page":"87","article-title":"Hookworm anthelmintic resistance: novel fecal polymerase chain reaction Ancylostoma caninum benzimidazole resistance marker detection in a dog","volume":"60","author":"Evason M","year":"2024","unstructured":"Evason M, DeBess E, Culwell N, Ogeer J, Leutenegger C. Hookworm anthelmintic resistance: novel fecal polymerase chain reaction Ancylostoma caninum benzimidazole resistance marker detection in a dog. J Am Anim Hosp Assoc. 2024;60(2):87\u201391. doi:10.5326\/JAAHA-MS-7366"},{"key":"B21","series-title":"Considerations for Extra-Label Use of Emodepside to Treat MADR Hookworms in Dogs","author":"Singler E","year":"2024","unstructured":"Singler E. Considerations for Extra-Label Use of Emodepside to Treat MADR Hookworms in Dogs. American Animal Hospital Association; 2024. Accessed October 4, 2024. https:\/\/www.aaha.org\/newstat\/publications\/considerations-for-extra-label-use-of-emodepside-to-treat-madr-hookworms-in-dogs\/"},{"issue":"3","key":"B22","series-title":"Adv Drug Deliv Rev","first-page":"175","article-title":"Potential and problems of developing transdermal patches for veterinary applications","volume":"50","author":"Riviere JE","year":"2001","unstructured":"Riviere JE, Papich MG. Potential and problems of developing transdermal patches for veterinary applications. Adv Drug Deliv Rev. 2001;50(3):175\u2013203. doi:10.1016\/S0169-409X(01)00157-0"},{"issue":"5","key":"B23","series-title":"J Invest Dermatol","first-page":"582","article-title":"Interspecies and interregional analysis of the comparative histologic thickness and laser doppler blood flow measurements at five cutaneous sites in nine species","volume":"95","author":"Monteiro-Riviere NA","year":"1990","unstructured":"Monteiro-Riviere NA, Bristol DG, Manning TO, Rogers RA, Riviere JE. Interspecies and interregional analysis of the comparative histologic thickness and laser doppler blood flow measurements at five cutaneous sites in nine species. J Invest Dermatol. 1990;95(5):582\u2013586. doi:10.1111\/1523-1747.ep12505567"},{"issue":"4","key":"B24","series-title":"J Vet Pharmacol Ther","first-page":"265","article-title":"Pharmacokinetics of selamectin following intravenous, oral and topical administration in cats and dogs","volume":"25","author":"Sarasola P","year":"2002","unstructured":"Sarasola P, Jernigan A, Walker D, Castledine J, Smith DG, Rowan TG. Pharmacokinetics of selamectin following intravenous, oral and topical administration in cats and dogs. J Vet Pharmacol Ther. 2002;25(4):265\u2013272. doi:10.1046\/j.1365-2885.2002.00415.x"},{"issue":"1\u20132","key":"B25","series-title":"Vet Parasitol","first-page":"120","article-title":"Comparative plasma disposition, bioavailability and efficacy of ivermectin following oral and pour-on administrations in horses","volume":"170","author":"Gokbulut C","year":"2010","unstructured":"Gokbulut C, Cirak VY, Senlik B, Aksit D, Durmaz M, McKellar QA. Comparative plasma disposition, bioavailability and efficacy of ivermectin following oral and pour-on administrations in horses. Vet Parasitol. 2010;170(1\u20132):120\u2013126. doi:10.1016\/j.vetpar.2010.01.041"},{"issue":"15","key":"B26","series-title":"Vet Rec","first-page":"575","article-title":"Failure of injectable ivermectin to control psoroptic mange in cattle","volume":"167","author":"Lekimme M","year":"2010","unstructured":"Lekimme M, Farnir F, Marechal F, Losson B. Failure of injectable ivermectin to control psoroptic mange in cattle. Vet Rec. 2010;167(15):575. doi:10.1136\/vr.c4906"},{"issue":"10","key":"B27","series-title":"Brit J Clin Pharmacol","first-page":"3949","article-title":"Safety, tolerability and pharmacokinetics of emodepside, a potential novel treatment for onchocerciasis (river blindness), in healthy male subjects","volume":"87","author":"Gillon JY","year":"2021","unstructured":"Gillon JY, Dennison J, van den Berg F, et al. Safety, tolerability and pharmacokinetics of emodepside, a potential novel treatment for onchocerciasis (river blindness), in healthy male subjects. Brit J Clin Pharmacol. 2021;87(10):3949\u20133960. doi:10.1111\/bcp.14816"},{"issue":"2","key":"B28","series-title":"J Pharm Pharm Sci","first-page":"217","article-title":"How critical is the duration of the sampling scheme for the determination of half-life, characterization of exposure and assessment of bioequivalence?","volume":"14","author":"Colucci P","year":"2011","unstructured":"Colucci P, Turgeon J, Ducharme MP. How critical is the duration of the sampling scheme for the determination of half-life, characterization of exposure and assessment of bioequivalence? J Pharm Pharm Sci. 2011;14(2):217\u2013226. doi:10.18433\/J3FG63"},{"key":"B29","author":"Dias CAR","year":"2014","unstructured":"Dias CAR. Possible emodepside toxicosis in a Collie with MDR1 gene mutation. Dissertation. Escola Universit\u00e1ria Vasco da Gama, 2014."},{"key":"B30","series-title":"Front Vet Sci","first-page":"296","article-title":"Adverse drug reactions after administration of emodepside\/praziquantel (Profender) in an MDR1-mutant Australian Shepherd dog: case report","volume":"6","author":"Gaens D","year":"2019","unstructured":"Gaens D, Leith\u00e4user C, Hamann M, Geyer J. Adverse drug reactions after administration of emodepside\/praziquantel (Profender) in an MDR1-mutant Australian Shepherd dog: case report. Front Vet Sci. 2019;6:296. doi:10.3389\/fvets.2019.00296"},{"issue":"6","key":"B31","series-title":"PLoS Pathogens","first-page":"e1009601","article-title":"Emodepside targets SLO-1 channels of Onchocerca ochengi and induces broad anthelmintic effects in a bovine model of onchocerciasis","volume":"17","author":"Bah GS","year":"2021","unstructured":"Bah GS, Schneckener S, Hahnel SR, et al. Emodepside targets SLO-1 channels of Onchocerca ochengi and induces broad anthelmintic effects in a bovine model of onchocerciasis. PLoS Pathogens. 2021;17(6):e1009601. doi:10.1371\/journal.ppat.1009601"},{"key":"B32","series-title":"Parasite","first-page":"19","article-title":"Pharmacokinetics of a novel endectoparasiticide topical formulation for cats, combining esafoxolaner, eprinomectin and praziquantel","volume":"28","author":"Jacquot V","year":"2021","unstructured":"Jacquot V, Buellet P, Letendre L, Tong W, Li H, Tielemans E. Pharmacokinetics of a novel endectoparasiticide topical formulation for cats, combining esafoxolaner, eprinomectin and praziquantel. Parasite. 2021;28:19. doi:10.1051\/parasite\/2021014"}],"container-title":["American Journal of Veterinary Research"],"original-title":[],"link":[{"URL":"https:\/\/avmajournals.avma.org\/view\/journals\/ajvr\/86\/7\/ajvr.25.01.0027.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/avmajournals.avma.org\/downloadpdf\/journals\/ajvr\/86\/7\/ajvr.25.01.0027.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/avmajournals.avma.org\/downloadpdf\/journals\/ajvr\/86\/7\/ajvr.25.01.0027.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T13:00:48Z","timestamp":1751461248000},"score":1,"resource":{"primary":{"URL":"https:\/\/avmajournals.avma.org\/view\/journals\/ajvr\/86\/7\/ajvr.25.01.0027.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,1]]},"references-count":32,"journal-issue":{"issue":"7"},"URL":"https:\/\/doi.org\/10.2460\/ajvr.25.01.0027","relation":{},"ISSN":["0002-9645","1943-5681"],"issn-type":[{"value":"0002-9645","type":"print"},{"value":"1943-5681","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,1]]}}}