{"id":10255,"date":"2021-10-03T19:30:00","date_gmt":"2021-10-03T17:30:00","guid":{"rendered":"https:\/\/www.fipwarriors.eu\/?p=10255"},"modified":"2023-03-29T09:49:23","modified_gmt":"2023-03-29T07:49:23","slug":"liecba-fip-peroralnymi-pripravkami-gs-441524","status":"publish","type":"post","link":"https:\/\/www.fipwarriors.eu\/en\/liecba-fip-peroralnymi-pripravkami-gs-441524\/","title":{"rendered":"FIP treatment with oral forms GS-441524"},"content":{"rendered":"<p class=\"has-small-font-size\">Niels C. Pedersen, Nicole Jacque,<br>3.10.2021<br>P&ocirc;vodn&yacute; &#269;l&aacute;nok: <a href=\"https:\/\/sockfip.org\/wp-content\/uploads\/2021\/11\/Use-of-oral-GS-441524-for-FIP-treatment-v10.pdf\" target=\"_blank\" rel=\"noreferrer noopener\"><\/a><a class=\"glossaryLink\" aria-describedby=\"tt\" data-cmtooltip=\"&lt;div class=glossaryItemBody&gt;Infek&#269;n&aacute; peritonit&iacute;da ma&#269;iek (angl. Feline infectious peritonitis, zau&#382;&iacute;van&aacute; skratka FIP) je infek&#269;n&eacute; ochorenie ma&#269;iek sp&ocirc;sobuj&uacute;ce smr&#357;. N&aacute;zov je mierne zav&aacute;dzaj&uacute;ci, preto&#382;e nejde o z&aacute;pal pobru&scaron;nice (&#269;i&#382;e peritonea), ale o z&aacute;pal ciev (vaskulit&iacute;da). Klinick&eacute; pr&iacute;znaky FIP sa v&scaron;ak &#269;asto prejavuj&uacute; vo forme z&aacute;palu pobru&scaron;nice. V&iacute;rus FIP nap&aacute;da v&scaron;ak aj pohrudnicu &ndash; z toho d&ocirc;vodu je niekedy choroba ozna&#269;ovan&aacute; tie&#382; ako Infek&#269;n&aacute; ma&#269;acia polyserozit&iacute;da (Feline infectious polyserositis).&lt;\/div&gt;\" href=\"https:\/\/www.fipwarriors.eu\/en\/glossary\/fip\/\" data-mobile-support=\"0\" data-gt-translate-attributes='[{\"attribute\":\"data-cmtooltip\", \"format\":\"html\"}]' tabindex=\"0\" role=\"link\">FIP<\/a> treatment with oral formulations of GS-441524<\/p>\n\n\n\n<h2 class=\"wp-block-heading\">&Uacute;vod<\/h2>\n\n\n\n<p>Po&#269;iato&#269;n&eacute; testovanie GS-441524 v ter&eacute;ne na lie&#269;bu FIP zah&#341;&#328;alo subkut&aacute;nnu aplik&aacute;ciu. Tento sp&ocirc;sob pod&aacute;vania bol zalo&#382;en&yacute; na predch&aacute;dzaj&uacute;cich farmakokinetick&yacute;ch (PK) &scaron;t&uacute;di&aacute;ch vykonan&yacute;ch na laborat&oacute;rnych ma&#269;k&aacute;ch. Intraven&oacute;zny a subkut&aacute;nny sp&ocirc;sob pod&aacute;vania injekcie priniesol podobn&eacute; vysok&eacute; hladiny v krvi, ktor&eacute; sa udr&#382;iavali v koncentr&aacute;ci&aacute;ch inhibuj&uacute;cich v&iacute;rusy viac ako 24 hod&iacute;n. Zistilo sa, &#382;e peror&aacute;lne podanie vedie k hladin&aacute;m v krvi, ktor&eacute; dosahuj&uacute; vrchol po 2 hodin&aacute;ch, ale dosahuj&uacute; len pribli&#382;ne 40 % vrcholov&yacute;ch hlad&iacute;n subkut&aacute;nnej a intraven&oacute;znej aplik&aacute;cie (Pedersen NC, nepublikovan&eacute; &uacute;daje, 2018). Psy, ktor&eacute; maj&uacute; dlh&scaron;&iacute; &#269;revn&yacute; trakt vyvinut&yacute; pre v&scaron;e&#382;ravcov, v&scaron;ak m&ocirc;&#382;u peror&aacute;lnou cestou absorbova&#357; a&#382; 85 % GS441524 <sup>[1, 5]<\/sup>. Psy sa v &scaron;t&uacute;di&aacute;ch peror&aacute;lnej absorpcie &#269;asto pou&#382;&iacute;vaj&uacute; ako n&aacute;hrada za &#318;ud&iacute;, tak&#382;e peror&aacute;lna absorpcia u &#318;ud&iacute; je tie&#382; pravdepodobne vy&scaron;&scaron;ia ako u ma&#269;iek.&nbsp;<\/p>\n\n\n\n<p>&#268;&iacute;nski dod&aacute;vatelia lieku GS-441524 skop&iacute;rovali riedidlo, koncentr&aacute;ciu lieku a sp&ocirc;sob subkut&aacute;nneho podania, ktor&eacute; boli pou&#382;it&eacute; v p&ocirc;vodnej publikovanej ter&eacute;nnej &scaron;t&uacute;dii. Prvou spolo&#269;nos&#357;ou, ktor&aacute; pon&uacute;kla GS441524 na neschv&aacute;lenom trhu, bola spolo&#269;nos&#357; Mutian. Spolo&#269;nos&#357; Mutian bola tie&#382; prv&aacute;, ktor&aacute; sk&uacute;mala a pon&uacute;kala peror&aacute;lnu formu lieku. V&yacute;skumn&iacute;ci spolo&#269;nosti Mutian zistili, &#382;e &uacute;&#269;inn&eacute; hladiny lieku GS-441524 v krvi mo&#382;no dosiahnu&#357; len zv&yacute;&scaron;en&iacute;m koncentr&aacute;cie lieku v ich peror&aacute;lnych pr&iacute;pravkoch. Ostatn&eacute; spolo&#269;nosti (napr. Aura, Lucky) n&aacute;sledne pon&uacute;kli svoje vlastn&eacute; verzie peror&aacute;lne pod&aacute;van&eacute;ho lieku GS-441524. Od septembra 2021 v&scaron;ak spolo&#269;nos&#357; Mutian na svojej webovej str&aacute;nke u&#382; neuv&aacute;dza peror&aacute;lne pr&iacute;pravky GS (v akejko&#318;vek forme). V s&uacute;&#269;asnosti s&uacute; v USA najpou&#382;&iacute;vanej&scaron;&iacute;mi peror&aacute;lnymi formami GS441524 pr&iacute;pravky Aura, Lucky a Capella.<\/p>\n\n\n\n<p>S&uacute;&#269;asn&eacute; zna&#269;ky kaps&uacute;l\/tablet sa pred&aacute;vaj&uacute; ako v&yacute;&#382;ivov&eacute; doplnky a na ich etiket&aacute;ch je uveden&yacute;ch nieko&#318;ko be&#382;n&yacute;ch ne&scaron;kodn&yacute;ch chemick&yacute;ch zl&uacute;&#269;en&iacute;n a lie&#269;iv&yacute;ch byl&iacute;n, pri&#269;om GS-441524 nie je medzi zlo&#382;kami v&ocirc;bec uveden&yacute;. Pravdepodobne sa tak deje preto, aby sa v&yacute;robcovia vyhli coln&yacute;m kontrol&aacute;m. Bez oh&#318;adu na zoznam zlo&#382;iek je &uacute;&#269;innou zlo&#382;kou v&scaron;etk&yacute;ch peror&aacute;lnych v&yacute;robkov GS-441524. Presn&uacute; koncentr&aacute;ciu GS-441524 v r&ocirc;znych peror&aacute;lnych pr&iacute;pravkoch predajcovia utajuj&uacute;, ale je zjavne vy&scaron;&scaron;ia (1,5 &ndash; 2-n&aacute;sobok?), ako by bolo potrebn&eacute;, keby sa liek pod&aacute;val podko&#382;ne.&nbsp;<\/p>\n\n\n\n<p>Spo&#269;iatku sme sa k or&aacute;lnej ceste stavali kriticky z dvoch d&ocirc;vodov. Po prv&eacute;, or&aacute;lne formy boli viac plytvaj&uacute;ce t&yacute;m, &#269;o bolo spo&#269;iatku vz&aacute;cnym a drah&yacute;m zdrojom. Po druh&eacute;, publikovan&yacute; v&yacute;skum peror&aacute;lnej absorpcie nukleozidov (GS-441524 je nukleozid) dokumentuje limitn&uacute; koncentr&aacute;ciu alebo strop pre peror&aacute;lnu absorpciu <sup>[2-5]<\/sup>. V&yacute;sledky s EIDD-1931, pr&iacute;buzn&yacute;m nukleozidom, uk&aacute;zali pokles biologickej dostupnosti z 56 na 36 % so zvy&scaron;ovan&iacute;m peror&aacute;lnej d&aacute;vky<sup> [6]<\/sup>. Toto obmedzenie by teoreticky s&#357;a&#382;ilo dosiahnutie extr&eacute;mne vysok&yacute;ch koncentr&aacute;ci&iacute; v krvi potrebn&yacute;ch na lie&#269;bu niektor&yacute;ch foriem FIP (napr. neurologick&yacute;ch) a\/alebo na prekonanie probl&eacute;mu z&iacute;skanej rezistencie na lieky. Peror&aacute;lnu biologick&uacute; dostupnos&#357; m&ocirc;&#382;u v&yacute;razne zn&iacute;&#382;i&#357; aj niektor&eacute; l&aacute;tky v potrave a majitelia ma&#269;iek s&uacute; zn&aacute;mi t&yacute;m, &#382;e pou&#382;&iacute;vaj&uacute; ve&#318;k&eacute; mno&#382;stvo doplnkov stravy, z ktor&yacute;ch niektor&eacute; by mohli negat&iacute;vne ovplyvni&#357; lie&#269;bu.&nbsp;<\/p>\n\n\n\n<p>Zd&aacute; sa, &#382;e &#269;oraz viac majite&#318;ov a veterin&aacute;rnych lek&aacute;rov vyu&#382;&iacute;va peror&aacute;lnu lie&#269;bu GS-441524 na &#269;as&#357; alebo cel&uacute; lie&#269;bu. N&aacute;klady na peror&aacute;lne pr&iacute;pravky GS-441524 sa za posledn&eacute; dva roky neust&aacute;le zni&#382;uj&uacute; a ich kvalita sa zvy&scaron;uje. Probl&eacute;m reakci&iacute; v mieste vpichu spolu s &uacute;&#269;innej&scaron;&iacute;mi peror&aacute;lnymi pr&iacute;pravkami GS-441524 stimulovali peror&aacute;lnu lie&#269;bu a &#269;oraz viac ma&#269;iek sa lie&#269;i peror&aacute;lnymi liekmi bu&#271; z &#269;asti, alebo &uacute;plne.&nbsp;<\/p>\n\n\n\n<h2 class=\"wp-block-heading\">Zlo&#382;enie a ozna&#269;enie<\/h2>\n\n\n\n<p>V&auml;&#269;&scaron;ina zaveden&yacute;ch peror&aacute;lnych pr&iacute;pravkov s&uacute; mal&eacute; tablety, ktor&eacute; sa pod&aacute;vaj&uacute; &#318;ah&scaron;ie ako v&auml;&#269;&scaron;ie kapsuly. Nov&scaron;ie pr&iacute;pravky, ako je Sweeper, pon&uacute;kaj&uacute; rozpustn&uacute; filmov&uacute; formu GS-441524, aby sa predi&scaron;lo &#357;a&#382;kostiam pri &bdquo;pilulkovan&iacute;&ldquo; u niektor&yacute;ch ma&#269;iek.&nbsp;<\/p>\n\n\n\n<p>Skuto&#269;n&eacute; mno&#382;stvo GS-441524 v tablete\/kapsule a predajcom odpor&uacute;&#269;an&eacute; d&aacute;vkovanie peror&aacute;lnych liekov sa zna&#269;ne l&iacute;&scaron;i pod&#318;a formy FIP, predajcu a sk&uacute;senost&iacute; majite&#318;a a skup&iacute;n lie&#269;iacich FIP. Preto sa skuto&#269;n&eacute; mno&#382;stvo (mg) GS-441524 v tablete alebo kapsule zvy&#269;ajne neuv&aacute;dza.&nbsp;&nbsp; Namiesto skuto&#269;n&eacute;ho mno&#382;stva GS-441524 v tablete alebo kapsule sa d&aacute;vkovanie predajcu &#269;asto zaklad&aacute; na po&#269;te tabliet potrebn&yacute;ch na kg hmotnosti, napr. 1 tableta\/kg per os (P0) ka&#382;d&yacute;ch (q)24 hod&iacute;n (h) pre ma&#269;ky s vlhkou alebo suchou FIP a bez okul&aacute;rneho alebo neurologick&eacute;ho postihnutia.&nbsp; Mno&#382;stvo GS-41524 v jednej takejto tablete podanej po 24 hodin&aacute;ch zodpoved&aacute; d&aacute;vke 4-6 mg\/kg SC po 24 hodin&aacute;ch, ale skuto&#269;n&eacute; mno&#382;stvo GS v jednej tablete m&ocirc;&#382;e by&#357; dvojn&aacute;sobn&eacute; ako v 1 ml injek&#269;n&eacute;ho GS, aby sa kompenzovala zn&iacute;&#382;en&aacute; biologick&aacute; dostupnos&#357; pri pod&aacute;van&iacute; peror&aacute;lnou cestou.&nbsp;<\/p>\n\n\n\n<p>Okrem toho m&aacute; jeden dod&aacute;vate&#318; (Aura\/Spark) tablety ozna&#269;en&eacute; na pod&aacute;vanie q12h a in&eacute; na d&aacute;vkovanie q24h. 1 tableta\/kg po 12 hodin&aacute;ch obsahuje polovi&#269;n&eacute; mno&#382;stvo GS-441524 (pravdepodobne 4 &ndash; 6 mg) ako 1 tableta\/kg po 24 hodin&aacute;ch (pravdepodobne 10 mg) &ndash; d&ocirc;vodom je, &#382;e d&aacute;vkovanie po 12 hodin&aacute;ch zabr&aacute;ni poklesu koncentr&aacute;cie v krvi pred 24 hodinami. &Uacute;&#269;inn&eacute; hladiny v krvi po jednorazovej d&aacute;vke PO alebo SC sa v&scaron;ak v oboch pr&iacute;padoch udr&#382;iavaj&uacute; 24 hod&iacute;n alebo dlh&scaron;ie. Pri d&aacute;vkach zodpovedaj&uacute;cich 10 &ndash; 15 mg\/kg SC q24h m&ocirc;&#382;e by&#357; &#271;al&scaron;ou v&yacute;hodou d&aacute;vkovanie q8h alebo q12h oproti q24h, preto&#382;e m&ocirc;&#382;e pom&ocirc;c&#357; ob&iacute;s&#357; absorp&#269;n&yacute; strop.&nbsp; Preto sa u ma&#269;iek s d&aacute;vkami zodpovedaj&uacute;cimi 10 &ndash; 15 mg\/kg SC q24h alebo vy&scaron;&scaron;&iacute;mi &#269;asto pou&#382;&iacute;va rozdelenie d&aacute;vok po d&aacute;vkovan&iacute; na q8h alebo q12h.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\">D&aacute;vkovanie<\/h2>\n\n\n\n<p>Odpor&uacute;&#269;an&eacute; za&#269;iato&#269;n&eacute; d&aacute;vkovanie GS-441524 pre ma&#269;ky s mokrou alebo suchou FIP a bez neurologick&yacute;ch alebo okul&aacute;rnych pr&iacute;znakov je 4-6 mg\/kg SC q24h. Injek&#269;n&aacute; d&aacute;vka pre ma&#269;ky s okul&aacute;rnym ochoren&iacute;m je 8 mg\/kg SC q24h a pre ma&#269;ky s neurologick&yacute;m ochoren&iacute;m 10 mg\/kg SC q24h.&nbsp; Ak sa u ma&#269;ky za&#269;ne lie&#269;ba vlhkej FIP a potom sa vyvinie ochorenie o&#269;&iacute;, d&aacute;vka sa okam&#382;ite zv&yacute;&scaron;i na 8 mg\/kg SC q24h a ak sa vyvin&uacute; neurologick&eacute; pr&iacute;znaky, zv&yacute;&scaron;i sa na 10 mg\/kg SC q24h. Ne&uacute;spe&scaron;n&aacute; lie&#269;ba FIP pri d&aacute;vkach vy&scaron;&scaron;&iacute;ch ako 15 mg\/kg SC q24h sved&#269;&iacute; o rezistencii na liek. D&aacute;vky PO zodpovedaj&uacute;ce 4-6, 8 a 10 mg\/kg SC q24h s&uacute; 10, 16 a 20 mg\/kg PO q24h. (Pozn&aacute;mka: niektor&eacute; peror&aacute;lne pr&iacute;pravky s&uacute; ozna&#269;en&eacute; ako ekvivalenty SC, ale v skuto&#269;nosti obsahuj&uacute; a&#382; dvojn&aacute;sobok uv&aacute;dzan&yacute;ch mg GS) Odpor&uacute;&#269;an&aacute; d&#314;&#382;ka lie&#269;by je 12 t&yacute;&#382;d&#328;ov, pri&#269;om d&aacute;vka sa zvy&scaron;uje, ak sa to pova&#382;uje za potrebn&eacute;. Je v&scaron;ak zn&aacute;me, &#382;e niektor&eacute; ma&#269;ky sa m&ocirc;&#382;u vylie&#269;i&#357; za 6 t&yacute;&#382;d&#328;ov s ktorouko&#318;vek formou GS-441524, viacer&eacute; za 8-10 t&yacute;&#382;d&#328;ov a takmer v&scaron;etky za 12 t&yacute;&#382;d&#328;ov. Mlad&eacute; ma&#269;ky s abdomin&aacute;lnou vlhkou FIP maj&uacute; tendenciu reagova&#357; najr&yacute;chlej&scaron;ie, ma&#269;ky so suchou FIP pomal&scaron;ie a ma&#269;ky s neurologickou FIP najpomal&scaron;ie. Preto je &bdquo;univerz&aacute;lnym&ldquo; odpor&uacute;&#269;an&iacute;m lie&#269;i&#357; ka&#382;d&uacute; ma&#269;ku s FIP bez oh&#318;adu na formu minim&aacute;lne 12 t&yacute;&#382;d&#328;ov. Denn&uacute; d&aacute;vku vo forme PO je mo&#382;n&eacute; rozdeli&#357; q12h, &#269;o m&ocirc;&#382;e by&#357; v&yacute;hodn&eacute; pri lie&#269;be vy&scaron;&scaron;&iacute;mi d&aacute;vkami, aby sa predi&scaron;lo absorp&#269;n&eacute;mu stropu. Lie&#269;ba SC a PO sa m&ocirc;&#382;e strieda&#357; q12h, aby sa zabr&aacute;nilo ve&#318;k&yacute;m injek&#269;n&yacute;m objemom.<\/p>\n\n\n\n<p>Peror&aacute;lne d&aacute;vkovanie GS je menej presn&eacute; ako pri injekci&aacute;ch.&nbsp; Tablety sa &#357;a&#382;ko delia, preto&#382;e maj&uacute; tendenciu drobi&#357; sa, tak&#382;e delenie na polovice je &#269;asto to najlep&scaron;ie, &#269;o sa d&aacute; urobi&#357;. Ak vypo&#269;&iacute;tan&aacute; d&aacute;vka po u&#382;it&iacute; spad&aacute; medzi uveden&eacute; d&aacute;vky v tablet&aacute;ch, odpor&uacute;&#269;a sa v&#382;dy zaokr&uacute;hli&#357; nahor na najbli&#382;&scaron;iu polovicu tablety.&nbsp;<\/p>\n\n\n\n<h2 class=\"wp-block-heading\">Pod&aacute;vanie<\/h2>\n\n\n\n<p>V&scaron;etky peror&aacute;lne zna&#269;ky maj&uacute; obdobn&eacute; pokyny na pod&aacute;vanie kaps&uacute;l alebo tabliet. Vo v&scaron;eobecnosti sa odpor&uacute;&#269;a polhodinov&yacute; p&ocirc;st pred a po podan&iacute; lieku. Mal&eacute; mno&#382;stvo pamlsku m&ocirc;&#382;e ma&#269;ky povzbudi&#357;, aby tablety u&#382;ili, a mnoh&eacute; ma&#269;ky ich skonzumuj&uacute;, ke&#271; sa im daj&uacute; na tanier obalen&eacute; v pamlsku (napr. Churu).&nbsp;<\/p>\n\n\n\n<h2 class=\"wp-block-heading\">N&aacute;klady<\/h2>\n\n\n\n<p>Cena peror&aacute;lneho GS sa za posledn&yacute; rok v&yacute;razne zn&iacute;&#382;ila. Napriek tomu je relat&iacute;vna cena peror&aacute;lneho GS-441524 o 20 &ndash; 40 % vy&scaron;&scaron;ia (v z&aacute;vislosti od dod&aacute;vate&#318;a) ako jeho injek&#269;n&aacute; verzia. &nbsp;<\/p>\n\n\n\n<h2 class=\"wp-block-heading\">Faktory ovplyv&#328;uj&uacute;ce peror&aacute;lnu a injek&#269;n&uacute; aplik&aacute;ciu&nbsp;<\/h2>\n\n\n\n<p>Ma&#269;ky, u ktor&yacute;ch sa moment&aacute;lne vyskytuje zvracanie\/regurgit&aacute;cia a hna&#269;ka, sa vo v&scaron;eobecnosti pova&#382;uj&uacute; za nevhodn&yacute;ch kandid&aacute;tov na peror&aacute;lnu lie&#269;bu liekom GS-441524. Preto sa ma&#269;k&aacute;m so z&aacute;va&#382;n&yacute;m gastrointestin&aacute;lnym ochoren&iacute;m &#269;asto za&#269;&iacute;naj&uacute; pod&aacute;va&#357; injekcie, aspo&#328; k&yacute;m sa tieto probl&eacute;my nevyrie&scaron;ia. V&auml;&#269;&scaron;ina &#318;ud&iacute;, najm&auml; v minulosti, za&#269;ala s injek&#269;n&yacute;m pod&aacute;van&iacute;m GS-441524. Injek&#269;n&aacute; forma je lacnej&scaron;ia a d&aacute;vkovanie je presnej&scaron;ie riaden&eacute;. Absorpcia GS-441524 je tie&#382; spo&#318;ahlivej&scaron;ia subkut&aacute;nnou cestou ako peror&aacute;lnou, &#269;o je &#269;asto rozhoduj&uacute;ci faktor pri po&#269;iato&#269;nej lie&#269;be ma&#269;iek, ktor&eacute; s&uacute; na za&#269;iatku &#357;a&#382;ko chor&eacute; a nestabiln&eacute;. To, &#269;i ma&#269;ka bude pokra&#269;ova&#357; v injek&#269;nom pod&aacute;van&iacute; lieku GS-441524, je &#269;asto podmienen&eacute; schopnos&#357;ou majite&#318;a aplikova&#357; injekcie &#269;o najefekt&iacute;vnej&scaron;&iacute;m sp&ocirc;sobom, ochotou ma&#269;ky prisp&ocirc;sobi&#357; sa bolesti pri injekcii a v&yacute;skytom injek&#269;n&yacute;ch r&aacute;n (l&eacute;zi&iacute;) v mieste aplik&aacute;cie. Peror&aacute;lne pod&aacute;van&eacute; lieky s&uacute; v tak&yacute;chto situ&aacute;ci&aacute;ch &#269;asto v&iacute;tanou &uacute;&#318;avou pre majite&#318;a aj ma&#269;acieho pacienta. Niektor&eacute; l&aacute;tky pod&aacute;van&eacute; peror&aacute;lne m&ocirc;&#382;u interferova&#357; s absorpciou GS-441524. Preto by ste sa mali vyhn&uacute;&#357; zaradeniu in&yacute;ch liekov a v&yacute;&#382;ivov&yacute;ch doplnkov, ak nie s&uacute; nevyhnutn&eacute; pre lie&#269;bu FIP.&nbsp;<\/p>\n\n\n\n<h2 class=\"wp-block-heading\">Porovnanie &uacute;spe&scaron;nosti lie&#269;by injek&#269;n&yacute;m a peror&aacute;lnym GS-441524 &nbsp;<\/h2>\n\n\n\n<p>Za predpokladu, &#382;e d&aacute;vkovanie je presne vypo&#269;&iacute;tan&eacute; a riadne nastaven&eacute;, &uacute;spe&scaron;nos&#357; peror&aacute;lneho lieku GS-441524 v s&uacute;&#269;asnosti reflektuje &uacute;spe&scaron;nos&#357; injek&#269;n&yacute;ch liekov. Napriek tomu boli zaznamenan&eacute; rozdiely v reakci&aacute;ch medzi peror&aacute;lnym a injek&#269;n&yacute;m GS-441524. Mal&yacute; po&#269;et ma&#269;iek nereagoval dobre na peror&aacute;lny GS-441524 ako po&#269;iato&#269;n&uacute; lie&#269;bu alebo viedol k relapsom pri nahraden&iacute; injekci&iacute;. Alternat&iacute;vne, prechod ma&#269;iek na peror&aacute;lny GS-441524 v ekvivalentnej d&aacute;vke viedol k vyrie&scaron;eniu ochorenia, ktor&eacute; nereagovalo dobre na injekcie. Je &#357;a&#382;k&eacute; priradi&#357; tieto dramatick&eacute; rozdiely v odpovedi liekovej forme, ke&#271;&#382;e GS-441524 pod&aacute;van&yacute; subkut&aacute;nnou alebo peror&aacute;lnou cestou sa dost&aacute;va do krvn&eacute;ho obehu a nakoniec do tkan&iacute;v. Je pravdepodobnej&scaron;ie, &#382;e je to sp&ocirc;soben&eacute; t&yacute;m, &#382;e zna&#269;ky injek&#269;n&eacute;ho alebo peror&aacute;lneho lieku GS-441524 pou&#382;&iacute;van&eacute; pred takouto zmenou neboli dobr&eacute; alebo &#382;e sa vyskytli probl&eacute;my s absorpciou alebo pod&aacute;van&iacute;m.&nbsp; Skuto&#269;ne sa vyskytlo mnoho pr&iacute;padov, ke&#271; prechod na in&uacute; peror&aacute;lnu alebo injek&#269;n&uacute; zna&#269;ku okam&#382;ite viedol k zlep&scaron;eniu odozvy.&nbsp;<\/p>\n\n\n\n<p>P&ocirc;vodne sa predpokladalo, &#382;e iba injek&#269;n&aacute; forma GS-441524 m&ocirc;&#382;e dosiahnu&#357; extr&eacute;mne vysok&eacute; hladiny v krvi a mozgovomiechovom moku potrebn&eacute; na &uacute;&#269;inn&uacute; lie&#269;bu neurologick&eacute;ho ochorenia, najm&auml; v situ&aacute;ci&aacute;ch, ke&#271; sa u v&iacute;rusu vyvinul r&ocirc;zny stupe&#328; rezistencie na lieky. Av&scaron;ak peror&aacute;lne zna&#269;ky, ako napr&iacute;klad Aura\/Lucky, boli &uacute;&#269;inn&eacute; u mnoh&yacute;ch ma&#269;iek s neurologickou FIP. T&yacute;kalo sa to aj niektor&yacute;ch ma&#269;iek, ktor&eacute; nereagovali na extr&eacute;mne vysok&eacute; d&aacute;vky injek&#269;nej formy GS441524. &#268;oraz viac ma&#269;iek s neurologickou FIP sa lie&#269;i v&yacute;lu&#269;ne peror&aacute;lnou formou GS. Je to sp&ocirc;soben&eacute; bu&#271; v&auml;&#269;&scaron;&iacute;mi sk&uacute;senos&#357;ami s peror&aacute;lnou lie&#269;bou v &#357;a&#382;k&yacute;ch pr&iacute;padoch FIP, alebo pravdepodobne vy&scaron;&scaron;ou kvalitou peror&aacute;lnych pr&iacute;pravkov.&nbsp;<\/p>\n\n\n\n<h2 class=\"wp-block-heading\">Preh&#318;ad v s&uacute;&#269;asnosti dostupn&yacute;ch zna&#269;iek peror&aacute;lnej formy GS-441524&nbsp;<\/h2>\n\n\n\n<p>Pozn&aacute;mka: Ozna&#269;enie a obsah GS odr&aacute;&#382;aj&uacute; inform&aacute;cie poskytnut&eacute; dod&aacute;vate&#318;mi a neboli nez&aacute;visle overen&eacute;.&nbsp;<\/p>\n\n\n\n<p><strong><em>Mutian <\/em><\/strong>&ndash; Ide o p&ocirc;vodn&uacute; a najzn&aacute;mej&scaron;iu zna&#269;ku or&aacute;lnej formy GS-441524. Pred&aacute;val sa v nieko&#318;k&yacute;ch r&ocirc;znych form&aacute;ch vr&aacute;tane viacer&yacute;ch foriem tabliet a kaps&uacute;l. Za&#269;iatkom roku 2021 pre&scaron;iel Mutian na formu tabliet, ozna&#269;en&yacute;ch ako 200 mg alebo 50 mg &bdquo;Mutian&ldquo; alebo &bdquo;Xraphconn&ldquo; &ndash; tie dod&aacute;vaj&uacute; ekvivalentn&uacute; SC d&aacute;vku 10, resp. 2,5 mg GS-441524. Tablety s&uacute; podstatne v&auml;&#269;&scaron;ie (priemer 8,5 mm) ako tablety in&yacute;ch dod&aacute;vate&#318;ov.&nbsp; V poslednom &#269;ase je ojedinele k dispoz&iacute;cii nov&aacute; formul&aacute;cia kaps&uacute;l. Od septembra 2021 u&#382; webov&aacute; str&aacute;nka spolo&#269;nosti Mutian nepon&uacute;ka mo&#382;nos&#357; PO. Pre v&scaron;etky peror&aacute;lne formy lieku Mutian dod&aacute;vate&#318; uv&aacute;dza d&aacute;vkovanie: 100 mg\/kg &bdquo;Mutian&ldquo; pre vlhk&uacute;\/such&uacute; FIP, 150 mg\/kg Mutian pre okul&aacute;rnu FIP a 200 mg\/kg pre neurologick&uacute; FIP.&nbsp;<\/p>\n\n\n\n<p><strong><em>Aura\/Spark &ndash;<\/em><\/strong> Aura je dlhodobo zaveden&aacute; zna&#269;ka a pred&aacute;va sa v tablet&aacute;ch, ktor&eacute; sa pod&aacute;vaj&uacute; ka&#382;d&yacute;ch 12 alebo 24 hod&iacute;n. Pred&aacute;vaj&uacute; sa vo verzi&aacute;ch q12h a q24h, av&scaron;ak medzi t&yacute;mito dvoma verziami nie je rozdiel v zlo&#382;en&iacute; (t. j. pred&#314;&#382;en&eacute; uvo&#318;&#328;ovanie at&#271;.). Skuto&#269;n&eacute; mno&#382;stvo GS-441524 v ka&#382;dej tablete sa neuv&aacute;dza, ale ozna&#269;enie a &uacute;&#269;inn&aacute; d&aacute;vka s&uacute; nasledovn&eacute;:<\/p>\n\n\n\n<p><\/p>\n\n\n\n<figure class=\"wp-block-table is-style-stripes\"><table><thead><tr><th>Ozna&#269;enie<\/th><th>Ekvivalent injek&#269;nej d&aacute;vky<\/th><th>Pokyny pre d&aacute;vkovanie<\/th><\/tr><\/thead><tbody><tr><td>Aura 12h-1kg<\/td><td>cca. 2.5 mg\/kg<\/td><td>Vlhk&aacute;\/such&aacute;: 1 tableta na kg dvakr&aacute;t denne<br>Okul&aacute;rna: 1,5 tablety na kg dvakr&aacute;t denne<br>Neurologick&aacute;: 2 tablety na kg dvakr&aacute;t denne&nbsp;&nbsp;<\/td><\/tr><tr><td>Aura 24h&ndash;1 kg<\/td><td>cca. 5 mg\/kg<\/td><td>Vlhk&aacute;\/such&aacute;: 1 tableta na kg denne<br>Okul&aacute;rna: 1,5 tablety na kg denne<br>Neurologick&aacute;: 2 tablety na kg denne&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;<\/td><\/tr><tr><td>Aura 12h&ndash;3 kg<\/td><td>cca. 7.5 mg\/kg<\/td><td>Vlhk&aacute;\/such&aacute;: 1 tableta na 3 kg dvakr&aacute;t denne<br>Okul&aacute;rna: 1,5 tablety na 3 kg dvakr&aacute;t denne<br>Neurologick&aacute;: 2 tablety na 3 kg dvakr&aacute;t denne&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;<\/td><\/tr><tr><td>Aura 24h&ndash;2 kg<\/td><td>cca. 10 mg\/kg<\/td><td>Vlhk&aacute;\/such&aacute;: 1 tableta na 2 kg dvakr&aacute;t denne<br>Okul&aacute;rna: 1,5 tablety na 2 kg dvakr&aacute;t denne<br>Neurologick&aacute;: 2 tablety na 2 kg dvakr&aacute;t denne&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;<\/td><\/tr><\/tbody><\/table><\/figure>\n\n\n\n<p>Ekvivalentn&aacute; peror&aacute;lna d&aacute;vka pre &gt;10 mg\/kg denne injek&#269;n&eacute;ho GS sa &uacute;merne zvy&scaron;uje.&nbsp; Tablety sa m&ocirc;&#382;u kombinova&#357; bez oh&#318;adu na ozna&#269;enie 12\/24h s pou&#382;it&iacute;m &uacute;&#269;innej injek&#269;nej d&aacute;vky &ndash; napr&iacute;klad 2,5 kg ma&#269;ka s vlhkou FIP by mohla u&#382;&iacute;va&#357; jednu tabletu 24h &ndash; 2 kg a jednu tabletu 12h -1 kg denne.<\/p>\n\n\n\n<p><strong><em>Lucky &ndash; <\/em><\/strong>Tablety Lucky s&uacute; ozna&#269;en&eacute; ako 24h &ndash; 1 kg (ekvivalentn&aacute; d&aacute;vka 5-6 mg\/kg SC) alebo 24h &ndash; 2 kg (ekvivalentn&aacute; d&aacute;vka pribli&#382;ne 10-12 mg\/kg SC) a &uacute;dajne maj&uacute; identick&eacute; zlo&#382;enie ako porovnate&#318;n&eacute; tablety Aura, hoci maj&uacute; in&yacute; tvar.&nbsp; V pr&iacute;pade FIP bez okul&aacute;rnych alebo neurologick&yacute;ch pr&iacute;znakov by ste mali pod&aacute;va&#357; jednu 1 kg tabletu denne na kg hmotnosti ma&#269;ky alebo jednu 2 kg tabletu na ka&#382;d&eacute; 2 kg, zaokr&uacute;hlen&eacute; na najbli&#382;&scaron;iu polovicu tablety. Po&#269;et tabliet na de&#328; vyn&aacute;sobte &#269;&iacute;slom 1,5 v pr&iacute;pade o&#269;n&yacute;ch alebo &#269;&iacute;slom 2 v pr&iacute;pade neurologick&yacute;ch foriem.&nbsp;<\/p>\n\n\n\n<figure class=\"wp-block-table is-style-stripes\"><table><thead><tr><th>Ozna&#269;enie<\/th><th>Ekvivalent injek&#269;nej d&aacute;vky<\/th><th>Pokyny na d&aacute;vkovanie pri vlhkej\/suchej FIP (d&aacute;vkovanie sa zdvojn&aacute;sobuje pre neuro\/okul&aacute;rnu FIP)<\/th><\/tr><\/thead><tbody><tr><td>Lucky 24h &ndash; 1 kg<\/td><td>cca. 5-6 mg<\/td><td>1 tableta na kg denne<\/td><\/tr><tr><td>Lucky 24h &ndash; 2 kg<\/td><td>cca. 10-12 mg<\/td><td>1 tableta na 2 kg denne<\/td><\/tr><\/tbody><\/table><\/figure>\n\n\n\n<p><strong><em>Capella <\/em><\/strong>&ndash; Capella vyr&aacute;ba dve ve&#318;kosti tabliet, 1 kg (d&aacute;vka 5 &ndash; 6 mg SC ekvivalentu) a 2 kg (d&aacute;vka 10 &ndash; 12 mg SC ekvivalentu). V pr&iacute;pade FIP bez okul&aacute;rnych alebo neurologick&yacute;ch pr&iacute;znakov by ste mali pod&aacute;va&#357; jednu 1 kg tabletu denne na kg hmotnosti ma&#269;ky alebo jednu 2 kg tabletu na ka&#382;d&eacute; 2 kg a zaokr&uacute;hli&#357; nahor na najbli&#382;&scaron;iu polovicu tablety. Po&#269;et tabliet na de&#328; vyn&aacute;sobte 1,5 v pr&iacute;pade okul&aacute;rnych alebo 2 v pr&iacute;pade neurologick&yacute;ch foriem.&nbsp;<\/p>\n\n\n\n<p><strong><em>Kitty Care <\/em><\/strong>&ndash; Ide o &#271;al&scaron;iu n&iacute;zkon&aacute;kladov&uacute; zna&#269;ku, ktor&aacute; teraz pon&uacute;ka injek&#269;n&uacute; aj peror&aacute;lnu formu lieku GS-441524. Predpoklad&aacute; sa, &#382;e ka&#382;d&aacute; tableta obsahuje ekvivalent 6 mg SC d&aacute;vky GS-441524.&nbsp;<\/p>\n\n\n\n<p><strong><em>Hero 16 &ndash;<\/em><\/strong>Ide o dobre zn&aacute;mu zna&#269;ku, ktor&aacute; sa dod&aacute;va v &#318;ahko aplikovate&#318;n&yacute;ch a delite&#318;n&yacute;ch tablet&aacute;ch ur&#269;en&yacute;ch na pod&aacute;vanie v d&aacute;vke jedna tableta na 2 kg hmotnosti, ako s&uacute; tablety Capella 2 kg. Ka&#382;d&aacute; tableta pravdepodobne obsahuje 16 mg GS-441524.&nbsp;<\/p>\n\n\n\n<p><strong><em>Rainman <\/em><\/strong>&ndash; T&aacute;to zna&#269;ka je popul&aacute;rna v &#268;&iacute;ne a zd&aacute; sa, &#382;e m&aacute; dobr&uacute; poves&#357; v krajin&aacute;ch, kde sa pou&#382;&iacute;va. Pred&aacute;va sa v tablet&aacute;ch s hmotnos&#357;ou 1 kg a 2 kg, o ktor&yacute;ch sa predpoklad&aacute;, &#382;e obsahuj&uacute; ekvivalent 5 &ndash; 6 mg a 10 &ndash; 12 mg SC GS-441524.&nbsp;<\/p>\n\n\n\n<p><strong><em>Mary<\/em><\/strong> &ndash; Mary sa pred&aacute;va v kapsul&aacute;ch, ktor&eacute; pravdepodobne obsahuj&uacute; ekvivalent 6 mg SC GS-441524<\/p>\n\n\n\n<p><strong><em>Additional brands<\/em><\/strong>&ndash; Panda, Pany, Sweeper, Sweeper film<\/p>\n\n\n\n<h2 class=\"wp-block-heading\">Referen&#269;n&eacute; &scaron;t&uacute;die o GI absorpcii nukleozidov podobn&yacute;ch GS-441524 a GS-441524<\/h2>\n\n\n\n<ol class=\"has-small-font-size wp-block-list\"><li>Thomas L. A precursor to remdesivir shows therapeutic potential for COVID-19. https:\/\/www.news-medical.net\/news\/20210209\/A-precursor-to-remdesivir-showstherapeuticpotential-for-COVID-19.aspx.<\/li><li>Painter GR, Bowen RA, Bluemling GR, et al. The prophylactic and therapeutic activity of a broadly active ribonucleoside analog in a murine model of intranasal venezuelan equine encephalitis virus infection. Antiviral Res. 2019;171:104597. doi:10.1016\/j.antiviral.2019.104597<br>After oral administration EIDD-1931 is quickly absorbed as evidenced by plasma T-max-values ranging between 0.5 and 1.0 h.Exposures are high (C-ma-xvalues range between 30 and 40&mu;M) and are dose dependent, but significantly less than dose proportional. The observation of decreasing bioavailability with increasing dose may indicate capacity limited absorption, a phenomenon that has been reported for other nucleosides (de Miranda et al., 1981). EIDD-1931, like most endogenous nucleosides and xenobiotic nucleoside analogs, is a highly polar, hydrophilic molecule (cLog P =&minus;2.2) and therefore likely to require functional transporters to cross cell membranes. This dependence would explain the capacity limited uptake seen in the pharmacokinetic studies done using the CD-1 mice. Earlier reports also indicated that nucleoside uptake into mouse intestinal epithelial cells is primarily mediated by sodium dependent concentrative nucleoside transporters (Cass et al., 1999; Vijayalakshmi and Belt, 1988).<\/li><li>Cass, C.E., Young, J.D., Baldwin, S.A., Cabrita, M.A., Graham, K.A., Griffiths, M.,Jennings, L.L., Mackey, J.R., Ng, A.M., Ritzel, M.W., Vickers, M.F., Yao, S.Y., 1999.Nucleoside transporters of mammalian cells. Pharm. Biotechnol. 12313&ndash;12352<\/li><li>de Miranda, P., Krasny, H.C., Page, D.A., Elion, G.B., 1981. The disposition of acyclovir indifferent species. J. Pharmacol. Exp. Ther. 219 (2), 309&ndash;315<\/li><li>Vijayalakshmi, D., Belt, J.A., 1988. Sodium-dependent nucleoside transport in mouse intestinal epithelial cells. Two transport systems with differing substrate specificities. Biol. Chem. 263 (36), 19419&ndash;19423.<\/li><li>Yan VC, Khadka S, Arthur K, Ackroyd JJ, Georgiou DK, Muller FL. Pharmacokinetics of Orally Administered GS-441524 in Dogs. bioRxiv, doi: https:\/\/doi.org\/10.1101\/2021.02.04.429674<\/li><li>FIP Warriors CZ\/SK, https:\/\/www.fipwarriors.eu\/, https:\/\/www.facebook.com\/groups\/fipczsk<\/li><\/ol>\n","protected":false},"excerpt":{"rendered":"<p>Nicole Jacque, Niels C. Pedersen ? About oral forms of GS-441524. Comparison of the efficacy of tablets with injectable forms of GS-441524. Overview of available brands <\/p>","protected":false},"author":1,"featured_media":5449,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_uag_custom_page_level_css":"","footnotes":""},"categories":[191,188,190],"tags":[],"class_list":["post-10255","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-dr-pedersen","category-preverejnost","category-preklady"],"featured_image_urls_v2":{"full":["https:\/\/www.fipwarriors.eu\/wp-content\/uploads\/2021\/02\/pillsspilled.jpg",1920,1080,false],"thumbnail":["https:\/\/www.fipwarriors.eu\/wp-content\/uploads\/2021\/02\/pillsspilled-150x150.jpg",150,150,true],"medium":["https:\/\/www.fipwarriors.eu\/wp-content\/uploads\/2021\/02\/pillsspilled-300x169.jpg",300,169,true],"medium_large":["https:\/\/www.fipwarriors.eu\/wp-content\/uploads\/2021\/02\/pillsspilled-768x432.jpg",525,295,true],"large":["https:\/\/www.fipwarriors.eu\/wp-content\/uploads\/2021\/02\/pillsspilled-1024x576.jpg",525,295,true],"1536x1536":["https:\/\/www.fipwarriors.eu\/wp-content\/uploads\/2021\/02\/pillsspilled-1536x864.jpg",1536,864,true],"2048x2048":["https:\/\/www.fipwarriors.eu\/wp-content\/uploads\/2021\/02\/pillsspilled.jpg",1920,1080,false],"trp-custom-language-flag":["https:\/\/www.fipwarriors.eu\/wp-content\/uploads\/2021\/02\/pillsspilled-16x9.jpg",16,9,true],"twentyseventeen-featured-image":["https:\/\/www.fipwarriors.eu\/wp-content\/uploads\/2021\/02\/pillsspilled.jpg",1920,1080,false],"twentyseventeen-thumbnail-avatar":["https:\/\/www.fipwarriors.eu\/wp-content\/uploads\/2021\/02\/pillsspilled-100x100.jpg",100,100,true],"woocommerce_thumbnail":["https:\/\/www.fipwarriors.eu\/wp-content\/uploads\/2021\/02\/pillsspilled-250x250.jpg",250,250,true],"woocommerce_single":["https:\/\/www.fipwarriors.eu\/wp-content\/uploads\/2021\/02\/pillsspilled-350x197.jpg",350,197,true],"woocommerce_gallery_thumbnail":["https:\/\/www.fipwarriors.eu\/wp-content\/uploads\/2021\/02\/pillsspilled-100x100.jpg",100,100,true]},"post_excerpt_stackable_v2":"<p>Nicole Jacque, Niels C. Pedersen ? O or&aacute;lnych form&aacute;ch GS-441524. Porovnanie &uacute;&#269;innosti tabliet s injek&#269;n&yacute;mi formami GS-441524. Preh&#318;ad dostupn&yacute;ch zna&#269;iek <\/p>\n","category_list_v2":"<a href=\"https:\/\/www.fipwarriors.eu\/en\/category\/dr-pedersen\/\" rel=\"category tag\">Dr. Pedersen<\/a>, <a href=\"https:\/\/www.fipwarriors.eu\/en\/category\/preverejnost\/\" rel=\"category tag\">Pre verejnos\u0165<\/a>, <a href=\"https:\/\/www.fipwarriors.eu\/en\/category\/preklady\/\" rel=\"category tag\">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\/02\/pillsspilled.jpg","author_info":{"display_name":"L. M.","author_link":"https:\/\/www.fipwarriors.eu\/en\/author\/starman\/"},"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.5 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Lie\u010dba FIP peror\u00e1lnymi formami GS-441524 - 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-peroralnymi-pripravkami-gs-441524\/\" \/>\n<meta property=\"og:locale\" content=\"en_GB\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Lie\u010dba FIP peror\u00e1lnymi formami GS-441524 - FIP Warriors CZ\/SK \u00ae\" \/>\n<meta property=\"og:description\" content=\"Nicole Jacque, Niels C. Pedersen ? O or&aacute;lnych form&aacute;ch GS-441524. Porovnanie &uacute;&#269;innosti tabliet s injek&#269;n&yacute;mi formami GS-441524. 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M.\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:label1\" content=\"Written by\" \/>\n\t<meta name=\"twitter:data1\" content=\"L. M.\" \/>\n\t<meta name=\"twitter:label2\" content=\"Estimated reading time\" \/>\n\t<meta name=\"twitter:data2\" content=\"15 minutes\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\\\/\\\/schema.org\",\"@graph\":[{\"@type\":\"Article\",\"@id\":\"https:\\\/\\\/www.fipwarriors.eu\\\/liecba-fip-peroralnymi-pripravkami-gs-441524\\\/#article\",\"isPartOf\":{\"@id\":\"https:\\\/\\\/www.fipwarriors.eu\\\/liecba-fip-peroralnymi-pripravkami-gs-441524\\\/\"},\"author\":{\"name\":\"L. 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