{"id":4458,"date":"2021-01-19T16:08:29","date_gmt":"2021-01-19T15:08:29","guid":{"rendered":"https:\/\/www.fipwarriors.eu\/?p=4458"},"modified":"2023-03-29T09:50:20","modified_gmt":"2023-03-29T07:50:20","slug":"liecba-fip-remdesivirom","status":"publish","type":"post","link":"https:\/\/www.fipwarriors.eu\/en\/liecba-fip-remdesivirom\/","title":{"rendered":"Treatment of FIP in cats with Remdesivir"},"content":{"rendered":"

Pôvodný článok: Treatment of <\/a>FIP<\/a> in cats with Remdesivir
Richard Malik DVSc PhD FACVSc FASM<\/p>\n\n\n\n

Až donedávna bola diagnóza FIP pre mačacieho pacienta rozsudkom smrti. Aj keď omega-interferón a polyprenyl imunostimulant vykazovali v niektorých prípadoch isté účinky, väčšina mačiek a mačiatok s diagnostikovanou FIP uhynula, alebo z dôvodu zlého stavu bola nutná eutanázia.<\/p>\n\n\n\n

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Obrázok 1. (A) BOVA Remdesivir rekonštituovaný a pripravený na liečbu. (B) Cesta, ktorú Remdesivir absolvuje intracelulárne, aby sa aktivoval ako GS-441524<\/figcaption><\/figure><\/div>\n\n\n\n

To všetko sa zmenilo pred niekoľkými rokmi, keď vyvrcholil celoživotný výskum FIP profesora Nielsa C. Pedersena z UC Davis. Niels najprv dokázal pomocou inhibítora proteázy GC-376 zachrániť životy niekoľkých mačiek s FIP, a čoskoro potom ukázal, že nukleozidový analóg GS-441524 je pri liečbe FIP ešte účinnejší, aj keď požadovaná dávka závisela na tom, či došlo k očnému postihnutiu alebo postihnutiu CNS<\/a>. GS-441524 bol liek vyvinutý americkou spoločnosťou Gilead, ktorá však bohužiaľ neprejavila záujem o ďalší výskum molekuly pre veterinárne využitie pri liečbe FIP. Aby sa vyplnilo prázdne miesto pre účinnú terapiu FIP, začali rôzne spoločnosti vyrábať GS-441524 a predávať ho na čiernom trhu. Aj keď to bolo veľmi drahé, dostupnosť kvalitného GS-441524 poskytovala odhodlaným majiteľom mačiek spôsob, ako zachrániť mačky s vlhkou alebo suchou FIP, hoci obstaranie tohto lieku bolo komplikované, zvyčajne spojené s pomocou facebookovej skupiny. Bohužiaľ pre milovníkov mačiek, APVMA a Australian Veterinary Practitioner Board sa nakoniec postarali o výrazné sťaženie importu GS-441524 a jeho použitia pre veterinárne účely, s represívnymi opatreniami pre veterinárnych lekárov, ktorí chceli pomáhať mačkám s FIP.<\/p>\n\n\n\n

Je iróniou, že riešenie tohto problému priniesla pandémia COVID 19. Spoločnosť Gilead vyvinula remdesivir (GS-5734) pre liečbu ľudskej koronavírusovej choroby. Tento liek dostal dočasnú registráciu TGA v júni 2020 na liečbu infekcií SARS-Cov-2 u ľudských pacientov. Tento proces by za normálnych okolností trval niekoľko rokov, ale COVID ho urýchlil. Remdesivir je v podstate GS-441524 s pridaním niekoľkých ďalších fosfátových skupín na zlepšenie intracelulárnej penetrácie (obrázok 1B). Pretože remdesivir je schváleným humánnym liekom, je možné ho použiť off-label aj vo veterinárnej praxi, ako je napríklad liečba FIP u mačiek. Tým sa obišli problémy s používaním nelicencovaného lieku zakúpeného na čiernom trhu a súvisiace problémy s nepreukázanou účinnosťou, čistotou a konzistenciou.<\/p>\n\n\n\n

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Obrázok 2. Suchá FIP s pyogranulomatóznym zápalom intraabdominálnych lymfatických uzlín<\/a>. Namiesto vykonania prieskumnej laparotómie, biopsie lymfatických uzlín, histológie a imunohistológie by mohlo byť nákladovo efektívnejšie vyskúšať 3-dennú intravenóznu liečbu Remdesivirom.<\/figcaption><\/figure><\/div>\n\n\n\n

Spoločnosti BOVA Aus sa podarilo zabezpečiť spoľahlivý zdroj remdesiviru. Štúdie v Austrálii určili dobu trvanlivosti a in vitro<\/a> potvrdili účinnosť proti koronavírusom. Posledných 6 týždňov ho používame v klinickej praxi pre liečbu FIP. Niektoré z týchto prípadov boli novodiagnostikované mačky, zatiaľ čo iné boli mačky, ktoré sa už zlepšili pomocou produktu GS-441524 získaného z čierneho trhu, ktorý sa stal následne nedostupným. Liečilo sa niekoľko prípadov vlhkej a suchej FIP. Aj na základe malého počtu mačiek sa zdá, že remdesivir je veľmi účinný pri liečbe infekcií FIP. Jeho subkutánna aplikácia je o niečo ľahšia v porovnaní s GS-441524, a zdá sa, že je o niečo menej bolestivá. Dodáva sa v 100 mg vialke, ktorá sa riedi s 9 ml sterilnej vody pre injekčné roztoky, čím sa získa roztok s koncentráciou 10 mg\/ml (10 ml vialka po rozriedení).<\/p>\n\n\n\n

U novodiagnostikovaných mačiek so závažným priebehom ochorenia sme sa rozhodli počas prvých 3 dní liečby pre intravenóznu aplikáciu remdesiviru vo vysokej počiatočnej dávke (10mg\/kg rozpustenej v 10ml fyziologického roztoku a podávanej počas 10 minút), čím sa dosiahol rýchly nástup antivírusového účinnku; Klinické príznaky mačiek sa počas úvodnej terapie výrazne zlepšili v priebehu 2 – 3 dní. Mačky potom prechádzajú na subkutánnu liečbu, zvyčajne pri nižšej dávke. Pre bežné prípady FIP sme používali 5-6 mg\/kg raz denne (SIUD), pretože sa predpokladá, že remdesivir je približne rovnako účinný ako GS-441524 (Niels Pedersen, osobná komunikácia). V prípade zjavného postihnutia očí sa doporučuje dávkovanie 8mg\/kg SID a mačkám s neurologickou FIP s príznakmi postihnutia CNS sa podáva 10mg\/kg SID. Liečba potom pokračuje aplikáciou denných subkutánnych injekcií ďalšie 2-3 mesiace. U mačiek, pre ktoré boli SC injekcie bolestivé, sme na sedáciu\/analgéziu použili gabapentín a\/alebo buprenorfín, a v niektorých prípadoch sme každých 5 dní zaviedli nový cefalický katéter, ktorý umožnil majiteľom intravenóznu aplikáciu. V situáciách, keď si majitelia nemohli dovoliť celú liečbu, alebo keď injekcie boli príliš bolestivé, sme po úvodnej terapii Remdesivirom použili meflochín (62,5 mg 2-3 krát týždenne; získaný od BOVA alebo miestnej lekárne) pre jeho antivirotický účinok založený na práci Jacqui Norrisa a kolegov z University of Sydney.<\/p>\n\n\n\n

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Obrázok 3. Ktorá mačka má FIP a je liečená remdesivirom?<\/figcaption><\/figure><\/div>\n\n\n\n

Hlavnou výhodou liečby FIP Remdesivirom je, že aktívna látka, ktorú používame, je prítomná v schválenom lieku pre humánne použitie. Ide len o vypísanie receptu s menom a adresou klienta, menom pacienta a dávkou, ktorá sa má podať. BOVA môže zvyčajne pripraviť a poskytnúť vialky ktorémukoľvek veterinárnemu lekárovi v Austrálii do 24-48 hodín.<\/strong> V súčasnosti sú náklady na 100mg vialku 250 dolárov plus GST a poštovné, aj keď je možné, že sa cena časom zníži z dôvodu väčsích odberov. Veríme, že väčšina majiteľov sa bude cítiť oveľa lepšie, ak získajú produkt od známej austrálskej spoločnosti, než aby posielali peniaze do zahraničia a dúfali, že sa lieky z čierneho trhu dostanú bezpečne z Číny do Austrálie.<\/p>\n\n\n\n

Veterinári, ktorí sa chcú dozvedieť viac o tejto možnosti liečby, alebo majú všeobecné otázky týkajúce sa FIP, ma môžu kontaktovať e-mailom (richard.malik@sydney.edu.au). Diagnóza FIP presahuje rámec tohto informačného bulletinu, ale mačky s efúznou formou sa najľahšie diagnostikujú cytologickým vyšetrením a analýzou výpotku, a následnou imunohistochémiou na VPDS, University of Sydney (ľahko zariadiť prostredníctvom Vetnostics, QML, ASAP , VetPath, Gribbles alebo IDEXX). Suchá FIP je problematickejšia, pretože zvyčajne vyžaduje presnú aspiračnú biopsiu pyogranulomatóznych lézií v pečeni, obličkách alebo brušných lymfatických uzlinách. Zistili sme, že 3 dni intravenóznej terapie Remdesivirom môžu byť použité ako nákladovo efektívny terapeutický test u mačiek so suchou FIP ako alternatíva k biopsii intraabdominálnych štruktúr pri prieskumnej laparotómii, pretože v prípadoch FIP dochádza k rýchlemu zlepšeniu väčšiny klinických príznakov.<\/strong> Ak sa veterinári nechcú do liečby Remdesivirom pustiť sami, môžeme doporučiť veterinárnych lekárov so záujmom o liečbu FIP, ktorí by radi takéto prípady prijali.<\/p>\n\n\n\n

Zdroje<\/h3>\n\n\n\n

Kim, Y.; Liu, H.; Galasiti Kankanamalage, A.C.; Weerasekara, S.; Hua, D.H.; Groutas, W.C.; Chang, K.O.; Pedersen, N.C. Reversal of the progression of fatal coronavirus infection in cats by a broad-spectrum coronavirus protease inhibitor. PLoS Pathog. 2016, 12, e1005531.<\/p>\n\n\n\n

Pedersen, N.C.; Kim, Y.; Liu, H.; Galasiti Kankanamalage, A.C.; Eckstrand, C.; Groutas, W.C.; Bannasch, M.; Meadows, J.M.; Chang, K.O. Efficacy of a 3C-like protease inhibitor in treating various forms of acquired feline infectious peritonitis. J. Feline Med. Surg. 2018, 20, 378–392.<\/p>\n\n\n\n

Murphy, B.G.; Perron, M.; Murakami, E.; Bauer, K.; Park, Y.; Eckstrand, C.; Liepnieks, M.; Pedersen, N.C. The nucleoside analog GS-441524 strongly inhibits feline infectious peritonitis (FIP) virus in tissue culture and experimental cat infection studies. Vet. Microbiol. 2018, 219, 226–233.<\/p>\n\n\n\n

Pedersen, N.C.; Perron, M.; Bannasch, M.; Montgomery, E.; Murakami, E.; Liepnieks, M.; Liu, H. Efficacy, and safety of the nucleoside analog GS-441524 for treatment of cats with naturally occurring feline infectious peritonitis. J. Feline Med. Surg. 2019, 21, 271–281<\/p>\n\n\n\n

Dickinson PJ, Bannasch M, Thomasy SM, et al. Antiviral treatment using the adenosine nucleoside analogue GS-441524 in cats with clinically diagnosed neurological feline infectious peritonitis. Journal of Veterinary Internal Medicine. 2020. doi: 10.1111\/jvim.15780.<\/p>\n\n\n\n

McDonagh, P.; Sheehy, P.A.; Norris, J.M. Identification and characterisation of small molecule inhibitors of feline coronavirus replication. Vet. Microbiol. 2014, 174, 438–447.<\/p>\n","protected":false},"excerpt":{"rendered":"

Richard Malik DVSc PhD FACVSc FASM ? Although GS-441524 is not approved, Covid-19 brought the approval of Remdesivir, which shows equal efficacy in the treatment of FIP and can be used off-label.<\/p>","protected":false},"author":1,"featured_media":4474,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_uag_custom_page_level_css":"","footnotes":""},"categories":[187,188,190],"tags":[175,176,179],"class_list":["post-4458","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-odborne","category-preverejnost","category-preklady","tag-fip","tag-liecba","tag-remdesivir"],"featured_image_urls_v2":{"full":["https:\/\/www.fipwarriors.eu\/wp-content\/uploads\/2021\/01\/cat-wallpaper-red-FHD.jpg",1920,1080,false],"thumbnail":["https:\/\/www.fipwarriors.eu\/wp-content\/uploads\/2021\/01\/cat-wallpaper-red-FHD-150x150.jpg",150,150,true],"medium":["https:\/\/www.fipwarriors.eu\/wp-content\/uploads\/2021\/01\/cat-wallpaper-red-FHD-300x169.jpg",300,169,true],"medium_large":["https:\/\/www.fipwarriors.eu\/wp-content\/uploads\/2021\/01\/cat-wallpaper-red-FHD-768x432.jpg",525,295,true],"large":["https:\/\/www.fipwarriors.eu\/wp-content\/uploads\/2021\/01\/cat-wallpaper-red-FHD-1024x576.jpg",525,295,true],"1536x1536":["https:\/\/www.fipwarriors.eu\/wp-content\/uploads\/2021\/01\/cat-wallpaper-red-FHD-1536x864.jpg",1536,864,true],"2048x2048":["https:\/\/www.fipwarriors.eu\/wp-content\/uploads\/2021\/01\/cat-wallpaper-red-FHD.jpg",1920,1080,false],"trp-custom-language-flag":["https:\/\/www.fipwarriors.eu\/wp-content\/uploads\/2021\/01\/cat-wallpaper-red-FHD-16x9.jpg",16,9,true],"twentyseventeen-featured-image":["https:\/\/www.fipwarriors.eu\/wp-content\/uploads\/2021\/01\/cat-wallpaper-red-FHD.jpg",1920,1080,false],"twentyseventeen-thumbnail-avatar":["https:\/\/www.fipwarriors.eu\/wp-content\/uploads\/2021\/01\/cat-wallpaper-red-FHD-100x100.jpg",100,100,true],"woocommerce_thumbnail":["https:\/\/www.fipwarriors.eu\/wp-content\/uploads\/2021\/01\/cat-wallpaper-red-FHD-250x250.jpg",250,250,true],"woocommerce_single":["https:\/\/www.fipwarriors.eu\/wp-content\/uploads\/2021\/01\/cat-wallpaper-red-FHD-350x197.jpg",350,197,true],"woocommerce_gallery_thumbnail":["https:\/\/www.fipwarriors.eu\/wp-content\/uploads\/2021\/01\/cat-wallpaper-red-FHD-100x100.jpg",100,100,true]},"post_excerpt_stackable_v2":"

Richard Malik DVSc PhD FACVSc FASM ? Aj keď GS-441524 nie je schválený, Covid-19 priniesol schválenie Remdesiviru, ktorý vykazuje rovnakú účinnosť pri liečbe FIP<\/a> a je možné jeho off-label použitie.<\/p>\n","category_list_v2":"Odborn\u00e9<\/a>, Pre verejnos\u0165<\/a>, Preklady<\/a>","author_info_v2":{"name":"LM","url":"https:\/\/www.fipwarriors.eu\/en\/author\/starman\/"},"comments_num_v2":"0 comments","featured_image_src":"https:\/\/www.fipwarriors.eu\/wp-content\/uploads\/2021\/01\/cat-wallpaper-red-FHD.jpg","author_info":{"display_name":"L. M.","author_link":"https:\/\/www.fipwarriors.eu\/en\/author\/starman\/"},"yoast_head":"\nLie\u010dba FIP remdesivirom - FIP Warriors CZ\/SK \u00ae<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.fipwarriors.eu\/en\/liecba-fip-remdesivirom\/\" \/>\n<meta property=\"og:locale\" content=\"en_GB\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Lie\u010dba FIP remdesivirom - FIP Warriors CZ\/SK \u00ae\" \/>\n<meta property=\"og:description\" content=\"Richard Malik DVSc PhD FACVSc FASM ? Aj keď GS-441524 nie je schválený, Covid-19 priniesol schválenie Remdesiviru, ktorý vykazuje rovnakú účinnosť pri liečbe FIP a je možné jeho off-label použitie.\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www.fipwarriors.eu\/en\/liecba-fip-remdesivirom\/\" \/>\n<meta property=\"og:site_name\" content=\"FIP Warriors CZ\/SK \u00ae\" \/>\n<meta property=\"article:publisher\" content=\"https:\/\/www.facebook.com\/groups\/fipczsk\" \/>\n<meta property=\"article:published_time\" content=\"2021-01-19T15:08:29+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2023-03-29T07:50:20+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/www.fipwarriors.eu\/wp-content\/uploads\/2021\/01\/cat-wallpaper-red-FHD.jpg\" \/>\n\t<meta property=\"og:image:width\" content=\"1920\" \/>\n\t<meta property=\"og:image:height\" content=\"1080\" \/>\n\t<meta property=\"og:image:type\" content=\"image\/jpeg\" \/>\n<meta name=\"author\" content=\"L. 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