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The safety of these two compounds, alone or in combination, was investigated in homozygous MDR1\u2010deficient collie dogs, in two studies. Overall, 30 adult collie dogs were treated once orally, 9 with a placebo, 9 with afoxolaner, 6 with MO, and 6 with a combination of afoxolaner and MO. For afoxolaner, the mean investigated dosage corresponded to 3.8 and 4.7 multiples of the maximum recommended therapeutic doses (RTD) in NexGard\u00ae and NexGard\u00ae Spectra, respectively. For MO, the mean investigated dosage corresponded to 4.7 multiples of the maximum RTD in NexGard\u00ae Spectra. Dogs were closely monitored for adverse reactions on the day of treatment and for the following two days. No significant adverse reaction was observed in any dog from the afoxolaner or the afoxolaner + MO groups; in the MO\u2010only treated group, mild and transient neurological signs were observed during the 4\u20138\u2009h post\u2010treatment window. These studies demonstrated a high level of safety of oral afoxolaner, alone or in combination with milbemycin oxime, in homozygous MDR1\u2010deficient dogs.<\/jats:p>","DOI":"10.1111\/jvp.13064","type":"journal-article","created":{"date-parts":[[2022,5,10]],"date-time":"2022-05-10T13:40:57Z","timestamp":1652190057000},"page":"373-379","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Safety of oral afoxolaner formulated with or without milbemycin oxime in homozygous<scp>MDR1<\/scp>\u2010deficient collie dogs"],"prefix":"10.1111","volume":"45","author":[{"given":"Marlene","family":"Drag","sequence":"first","affiliation":[{"name":"Boehringer Ingelheim Animal Health, Missouri Research Center Fulton Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Tielemans","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Animal Health Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Animal Health Athens Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,5,10]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0304\u20104017(00)00289\u20102"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI70430"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.2183\/pjab.87.13"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12917\u2010017\u20101251\u20109"},{"issue":"12","key":"e_1_2_10_6_1","first-page":"1165","article-title":"Pharmacogenetics: It's not just about ivermectin in collies","volume":"47","author":"Dowling P.","year":"2006","journal-title":"The Canadian Veterinary journal = La revue V\u00e9t\u00e9rinaire Canadienne"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetpar.2014.02.022"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/jvp.12375"},{"key":"e_1_2_10_9_1","volume-title":"CVMP Scientific discussion for Advocate (EMEA\/V\/C\/000076)","author":"EMA","year":"2009"},{"key":"e_1_2_10_10_1","volume-title":"CVMP assessment report for Bravecto (EMEA\/V\/C\/002526\/0000)","author":"EMA","year":"2013"},{"key":"e_1_2_10_11_1","volume-title":"CVMP assessment report for NexGard (EMEA\/V\/C\/002729\/0000)","author":"EMA","year":"2013"},{"key":"e_1_2_10_12_1","volume-title":"CVMP assessment report for NexGard spectra (EMEA\/V\/C\/003842\/0000)","author":"EMA","year":"2014"},{"key":"e_1_2_10_13_1","volume-title":"CVMP assessment report for Simparica (EMEA\/V\/C\/003991\/0000)","author":"EMA","year":"2015"},{"key":"e_1_2_10_14_1","volume-title":"CVMP assessment report for Credelio plus (EMEA\/V\/C\/005325\/0000)","author":"EMA","year":"2015"},{"key":"e_1_2_10_15_1","volume-title":"CVMP Scientific discussion for Simparica Trio (EMEA\/V\/C\/004846)","author":"EMA","year":"2021"},{"key":"e_1_2_10_16_1","first-page":"141","volume-title":"Freedom of information summary","author":"FDA","year":"2013"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.2174\/138920112800399301"},{"key":"e_1_2_10_18_1","first-page":"2","volume-title":"Proceedings of: Tagung der DVG\u2010 fachgruppe parasitologie und parasit\u00e4re krankheiten: Veterin\u00e4rparasitologie: neue forschungsergebnisse und aktuelle probleme in der praxis","author":"Geyer J.","year":"2018"},{"issue":"5","key":"e_1_2_10_19_1","first-page":"581","article-title":"Disposition of ivermectin and cyclosporin a in CF\u20101 mice deficient in mdr1a P\u2010glycoprotein","volume":"27","author":"Kwei G. 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