P\u0159esto\u017ee jsou injekce obecn\u011b pova\u017eov\u00e1ny za spolehliv\u011bj\u0161\u00ed ne\u017e peror\u00e1ln\u00ed forma GS-441524 pro l\u00e9\u010dbu FIP, \u0159ada majitel\u016f ko\u010dek se rozhoduje pro peror\u00e1ln\u00ed variantu, aby se vyhnuli p\u0159\u00edpadn\u00fdm nep\u0159\u00edjemn\u00fdm pocit\u016fm, kter\u00e9 mohou b\u00fdt spojeny s injekcemi.
\nN\u011bkter\u00e9 ko\u010dkovit\u00e9 \u0161elmy mohou po del\u0161\u00ed dob\u011b l\u00e9\u010dby poci\u0165ovat nepohodl\u00ed nebo si vyp\u011bstovat odpor k injekc\u00edm a jsou i takov\u00e9, kter\u00e9 se mohou proti tomuto postupu d\u016frazn\u011b ohradit.
\nKrom\u011b toho existuje mo\u017enost vzniku v\u0159ed\u016f v m\u00edst\u011b vpichu v d\u016fsledku kyselosti l\u00e9ku.
\nV t\u011bchto situac\u00edch lze jako n\u00e1hradu injekc\u00ed pou\u017e\u00edt peror\u00e1ln\u00ed tobolky nebo FIP tablety.
\nV p\u0159\u00edpad\u011b peror\u00e1ln\u00edho pod\u00e1v\u00e1n\u00ed nen\u00ed t\u0159eba se ob\u00e1vat rezistence na l\u00e9k.
\n\u00da\u010dinnost p\u0159\u00edpravku GS-441524 p\u0159i l\u00e9\u010db\u011b mokr\u00e9 i such\u00e9 formy FIP je konzistentn\u00ed bez ohledu na formu, ve kter\u00e9 je u\u017e\u00edv\u00e1n.
\nP\u0159i prvn\u00edch testech p\u0159\u00edpravku GS-441524 pro l\u00e9\u010dbu FIP v ter\u00e9nu byl pod\u00e1v\u00e1n injek\u010dn\u011b pod k\u016f\u017ei.
\nIntraven\u00f3zn\u00ed i subkut\u00e1nn\u00ed injekce vedly k vysok\u00fdm hladin\u00e1m v krvi, kter\u00e9 se udr\u017eely na \u00farovni, kter\u00e1 zastavila virus po dobu del\u0161\u00ed ne\u017e 24 hodin.
\nV\u00fdzkumn\u00edci tak\u00e9 zjistili, \u017ee pod\u00e1n\u00ed l\u00e9ku \u00fasty zv\u00fd\u0161ilo hladinu v krvi, ale stalo se tak o n\u011bco pozd\u011bji a pouze na \u00farovni asi 40 % maxim\u00e1ln\u00edch hladin pozorovan\u00fdch p\u0159i subkut\u00e1nn\u00ed a intraven\u00f3zn\u00ed cest\u011b (Pedersen NC, soukrom\u00e9 \u00fadaje, 2018).
\nPsi s del\u0161\u00edmi st\u0159evy, kte\u0159\u00ed se vyvinuli tak, aby mohli j\u00edst maso i rostliny, v\u0161ak mohou p\u0159ij\u00edmat a\u017e 85 % GS441524 potravou [1, 5].
\nStudie absorpce z \u00fast \u010dasto pou\u017e\u00edvaly psy jako n\u00e1hradn\u00edky lid\u00ed.
\nTo znamen\u00e1, \u017ee absorpce \u00fasty u lid\u00ed je pravd\u011bpodobn\u011b tak\u00e9 vy\u0161\u0161\u00ed ne\u017e u ko\u010dek.
\nProto byl pro testy v ter\u00e9nu na ko\u010dk\u00e1ch zvolen subkut\u00e1nn\u00ed zp\u016fsob, proto\u017ee se snadno pou\u017e\u00edv\u00e1 a d\u00e1v\u00e1 vysok\u00e9 hladiny v krvi.
\n\u010c\u00edn\u0161t\u00ed prodejci p\u0159\u00edpravku GS-441524 okop\u00edrovali publikovanou ter\u00e9nn\u00ed zkou\u0161ku \u0159edidla, koncentrace l\u00e9\u010diva a subkut\u00e1nn\u00ed zp\u016fsob pod\u00e1n\u00ed.
\nN\u00e1sledn\u011b l\u00e9k studuj\u00ed a nab\u00edzej\u00ed jej ve form\u011b tablet.
\nV\u00fdzkumn\u00edci v \u010c\u00edn\u011b zjistili, \u017ee mohou dos\u00e1hnout \u00fa\u010dinn\u00fdch hladin GS-441524 v krvi jen t\u00edm, \u017ee jejich peror\u00e1ln\u00ed verze budou obsahovat v\u00edce l\u00e9\u010diva.
\nPot\u00e9 p\u0159i\u0161ly dal\u0161\u00ed spole\u010dnosti s vlastn\u00edmi verzemi p\u0159\u00edpravku GS-441524, kter\u00e9 lze u\u017e\u00edvat \u00fasty.
\nSpot\u0159ebitel\u00e9 si nyn\u00ed mohou koupit tobolky a tablety.
\nNa etiket\u00e1ch je jako slo\u017eky uvedena \u0159ada popul\u00e1rn\u00edch, bezpe\u010dn\u00fdch chemick\u00fdch l\u00e1tek a l\u00e9\u010div\u00fdch bylin, ale GS-441524 mezi nimi nen\u00ed.
\nCeln\u00edci se na to pravd\u011bpodobn\u011b bl\u00ed\u017ee ned\u00edvaj\u00ed.
\nGS-441524 je \u00fa\u010dinnou l\u00e1tkou ve ve\u0161ker\u00e9m peror\u00e1ln\u00edm zbo\u017e\u00ed bez ohledu na to, co dal\u0161\u00edho se v n\u011bm nach\u00e1z\u00ed.
\nSpole\u010dnosti, kter\u00e9 prod\u00e1vaj\u00ed sublingv\u00e1ln\u00ed zbo\u017e\u00ed, neuv\u00e1d\u011bj\u00ed, kolik GS-441524 v n\u011bm je, ale je jasn\u00e9, \u017ee je to mnohem v\u00edce, ne\u017e kolik by bylo pot\u0159eba, kdyby se l\u00e9k pod\u00e1val pod k\u016f\u017ei.
\nVypad\u00e1 to, \u017ee st\u00e1le v\u00edce majitel\u016f dom\u00e1c\u00edch zv\u00ed\u0159at a veterin\u00e1\u0159\u016f pou\u017e\u00edv\u00e1 peror\u00e1ln\u00ed GS-441524 jako sou\u010d\u00e1st nebo celou l\u00e9\u010dbu.
\nZa posledn\u00ed dva roky se kvalita peror\u00e1ln\u00edch p\u0159\u00edpravk\u016f GS-441524 zv\u00fd\u0161ila, zat\u00edmco cena pomalu kles\u00e1.
\nVzhledem k probl\u00e9mu s reakcemi v m\u00edst\u011b vpichu a skute\u010dnosti, \u017ee peror\u00e1ln\u00ed p\u0159\u00edpravky GS-441524 funguj\u00ed l\u00e9pe, se l\u00e9\u010dba \u00fasty stala popul\u00e1rn\u011bj\u0161\u00ed.
\nSt\u00e1le v\u00edce ko\u010dek je l\u00e9\u010deno l\u00e9ky, kter\u00e9 se u\u017e\u00edvaj\u00ed \u00fasty, a to bu\u010f po \u010d\u00e1st l\u00e9\u010dby, nebo po celou dobu l\u00e9\u010dby.<\/p>\n
GS-441524 pro peror\u00e1ln\u00ed pou\u017eit\u00ed obsahuje mnohem v\u00edce GS441524 jako \u00fa\u010dinn\u00e9 l\u00e1tky, aby se vyrovnala ztr\u00e1ta absorpce.
\nV\u0161echny zn\u00e1m\u00e9 p\u0159\u00edpravky pro peror\u00e1ln\u00ed pod\u00e1n\u00ed jsou tablety.
\nTablety FIPMed jsou v\u0161ak men\u0161\u00edch rozm\u011br\u016f, tak\u017ee se l\u00e9pe konzumuj\u00ed.
\nN\u011bkter\u00e9 peror\u00e1ln\u00ed l\u00e9ky FIP jsou kapsle, kter\u00e9 jsou tak\u00e9 napln\u011bny tekutinou nebo pr\u00e1\u0161kem, a pokud je ko\u010dky rozkou\u0161ou, mohou o l\u00e9k uvnit\u0159 p\u0159ij\u00edt.
\nKdy\u017e ko\u010dky tablety rozlom\u00ed, je zn\u00e1mo, \u017ee maj\u00ed \u0161patn\u00e9 reakce.
\nPokyny pro u\u017e\u00edv\u00e1n\u00ed tablet nebo tablet jsou u v\u0161ech peror\u00e1ln\u00edch typ\u016f stejn\u00e9.
\nObvykle je nejlep\u0161\u00ed 30 minut p\u0159ed a po pod\u00e1n\u00ed l\u00e9ku nic nej\u00edst ani nep\u00edt.
\nN\u011bkter\u00e9 ko\u010dky mohou b\u00fdt ochotn\u00e9 je vz\u00edt, pokud jim d\u00e1te mal\u00fd pamlsek, a mnoho ko\u010dek je sn\u00ed, pokud je d\u00e1te na tal\u00ed\u0159ek s kryc\u00edm pamlskem (nap\u0159. Churu).
\nI kdy\u017e jsou peror\u00e1ln\u00ed kapsle i tablety stejn\u011b \u00fa\u010dinn\u00e9, pod\u00e1v\u00e1n\u00ed kapsl\u00ed je obecn\u011b obt\u00ed\u017en\u011bj\u0161\u00ed ne\u017e pod\u00e1v\u00e1n\u00ed tablet.
\nKapsle jsou v\u011bt\u0161\u00ed, tak\u017ee je pro ko\u010dky obt\u00ed\u017en\u00e9 je bez n\u00e1mahy spolknout.
\nStla\u010den\u00ed pr\u00e1\u0161kov\u00e9 formy do tablet vy\u017eaduje v\u011bt\u0161\u00ed v\u00fdrobn\u00ed kapacity, zat\u00edmco zadn\u00ed amat\u00e9rsk\u00e1 v\u00fdroba vyu\u017e\u00edv\u00e1 lidskou pr\u00e1ci k vlo\u017een\u00ed pr\u00e1\u0161ku do kapsl\u00ed.
\nPeror\u00e1ln\u00ed tablety FIPMED jsou ve srovn\u00e1n\u00ed s t\u011bmi na trhu men\u0161\u00ed, p\u0159esto obsahuj\u00ed vysok\u00e9 vst\u0159ebateln\u00e9 mno\u017estv\u00ed GS441524.
\nProd\u00e1vaj\u00ed se v koncentrac\u00edch 30 mg a 40 mg, ne jako ty 5mg na trhu, kter\u00e9 je t\u0159eba pro stejn\u00fd \u00fa\u010dinek opat\u0159it v\u00edce tabletami.
\nJsou kompaktn\u00ed a lze je snadno pod\u00e1vat ve v\u011bt\u0161in\u011b situac\u00ed.<\/p>\n
V uplynul\u00e9m roce se cena or\u00e1ln\u00edho GS hodn\u011b sn\u00ed\u017eila.
\nKdy\u017e u\u017e mluv\u00edme o cen\u00e1ch, peror\u00e1ln\u00ed GS-441524 je o 20-40 % dra\u017e\u0161\u00ed ne\u017e jeho injek\u010dn\u00ed prot\u011bj\u0161ek, nicm\u00e9n\u011b tablety spole\u010dnosti FIPMed jsou nejdostupn\u011bj\u0161\u00ed na trhu a stoj\u00ed t\u00e9m\u011b\u0159 stejn\u011b jako injek\u010dn\u00ed p\u0159\u00edpravky.<\/p>\n
Peror\u00e1ln\u00ed pod\u00e1n\u00ed GS-441524 obvykle nen\u00ed vhodn\u00e9 pro ko\u010dky, kter\u00e9 ji\u017e zvrac\u00ed nebo \u0159\u00edhaj\u00ed a maj\u00ed pr\u016fjem.
\nLid\u00e9 \u010dasto pod\u00e1vaj\u00ed ko\u010dk\u00e1m s velk\u00fdmi za\u017e\u00edvac\u00edmi probl\u00e9my injekce, dokud probl\u00e9my nezmiz\u00ed.
\nSubkut\u00e1nn\u00ed pod\u00e1n\u00ed GS-441524 je tak\u00e9 spolehliv\u011bj\u0161\u00ed ne\u017e peror\u00e1ln\u00ed pod\u00e1n\u00ed.
\nTo je \u010dasto velmi d\u016fle\u017eit\u00fd faktor v po\u010d\u00e1te\u010dn\u00ed p\u00e9\u010di o ko\u010dky, kter\u00e9 jsou velmi nemocn\u00e9 a nestabiln\u00ed.
\nP\u0159i rozhodov\u00e1n\u00ed, zda ko\u010dce nad\u00e1le pod\u00e1vat injek\u010dn\u00ed p\u0159\u00edpravek GS-441524, \u010dasto z\u00e1le\u017e\u00ed na tom, jak dob\u0159e majitel dok\u00e1\u017ee injekce prov\u00e1d\u011bt, jak je ko\u010dka p\u0159ipravena zvyknout si na bolest a jak \u010dasto se objevuj\u00ed r\u00e1ny v m\u00edst\u011b vpichu.
\nPokud k tomu dojde, je peror\u00e1ln\u00ed pod\u00e1n\u00ed l\u00e9ku \u010dasto p\u0159\u00edjemn\u00fdm odpo\u010dinkem pro majitele i ko\u010dku.<\/p>\n
Peror\u00e1ln\u00ed l\u00e9\u010dba FIP m\u016f\u017ee b\u00fdt p\u0159i pod\u00e1v\u00e1n\u00ed ve vhodnou dobu a ve vhodn\u00e9 d\u00e1vce stejn\u011b \u00fa\u010dinn\u00e1 jako podko\u017en\u00ed injekce p\u0159i \u0159e\u0161en\u00ed ko\u010di\u010d\u00ed infek\u010dn\u00ed peritonitidy.
\nNa druhou stranu se odborn\u00edci na l\u00e9\u010dbu FIP obecn\u011b shoduj\u00ed, \u017ee ko\u010dky l\u00e9\u010den\u00e9 peror\u00e1ln\u011b maj\u00ed v\u011bt\u0161\u00ed \u0161anci na recidivu ve srovn\u00e1n\u00ed s ko\u010dkami l\u00e9\u010den\u00fdmi injek\u010dn\u011b po celou dobu l\u00e9\u010dby.
\nPeror\u00e1ln\u00ed kapsle a tablety nemus\u00ed poskytovat optim\u00e1ln\u00ed l\u00e9\u010dbu pro ko\u010dky s neurologick\u00fdmi formami FIP nebo pro ko\u010dky, u kter\u00fdch doch\u00e1z\u00ed k \u010dast\u00e9mu zvracen\u00ed nebo pr\u016fjmu.
\nV sou\u010dasn\u00e9 dob\u011b nejsou hl\u00e1\u0161eny \u017e\u00e1dn\u00e9 ne\u017e\u00e1douc\u00ed \u00fa\u010dinky spojen\u00e9 s injek\u010dn\u00ed ani peror\u00e1ln\u00ed l\u00e9\u010dbou FIP.
\nN\u011bkter\u00e9 ko\u010dky nereagovaly dob\u0159e na u\u017e\u00edv\u00e1n\u00ed GS-441524 \u00fasty jako prvn\u00ed l\u00e9\u010dbu nebo u nich do\u0161lo k recidiv\u011b, kdy\u017e p\u0159e\u0161ly z injekc\u00ed na tablety.
\nV jin\u00fdch p\u0159\u00edpadech pod\u00e1v\u00e1n\u00ed stejn\u00e9ho mno\u017estv\u00ed p\u0159\u00edpravku GS-441524 \u00fasty vyl\u00e9\u010dilo onemocn\u011bn\u00ed ko\u010dek, kter\u00e9 nereagovaly dob\u0159e na injekce.
\nDoporu\u010dujeme v\u0161ak injek\u010dn\u00ed formu p\u0159\u00edpravku GS-441524, kter\u00e1 by mohla dos\u00e1hnout p\u0159esn\u00e9ho mno\u017estv\u00ed pot\u0159ebn\u00e9ho k l\u00e9\u010db\u011b onemocn\u011bn\u00ed Neuro FIP, zejm\u00e9na pokud se virus stal rezistentn\u00edm na r\u016fzn\u00e9 l\u00e9ky. \u00a0 Referen\u010dn\u00ed studie o absorpci nukleosid\u016f p\u0159\u00edbuzn\u00fdch GS-441524 a GS-441524 v tr\u00e1vic\u00edm traktu 1. Thomas L. Prekurzor remdesiviru vykazuje terapeutick\u00fd potenci\u00e1l pro COVID-19. https:\/\/www.news-medical.net\/news\/20210209\/A-precursor-to-remdesivir-showstherapeuticpotential-for-COVID-19.aspx. 2. Painter GR, Bowen RA, Bluemling GR, et al. Profylaktick\u00e1 a terapeutick\u00e1 aktivita \u0161iroce aktivn\u00edho ribonukleosidov\u00e9ho analogu na my\u0161\u00edm modelu intranaz\u00e1ln\u00ed infekce venezuelsk\u00fdm virem ko\u0148sk\u00e9 encefalitidy. Antiviral Res. 2019;171:104597. doi:10.1016\/j.antiviral.2019.104597 Po peror\u00e1ln\u00edm pod\u00e1n\u00ed se EIDD-1931 rychle vst\u0159eb\u00e1v\u00e1, o \u010dem\u017e sv\u011bd\u010d\u00ed plazmatick\u00e9 hodnoty T-max v rozmez\u00ed 0,5 a\u017e 1,0 h. Expozice jsou vysok\u00e9 (hodnoty C-ma-x se pohybuj\u00ed mezi 30 a 40 \u03bcM) a jsou z\u00e1visl\u00e9 na d\u00e1vce, ale v\u00fdrazn\u011b m\u00e9n\u011b ne\u017e d\u00e1vce \u00fam\u011brn\u00e9. Pozorov\u00e1n\u00ed klesaj\u00edc\u00ed biologick\u00e9 dostupnosti s rostouc\u00ed d\u00e1vkou m\u016f\u017ee nazna\u010dovat kapacitn\u011b omezenou absorpci, co\u017e je jev, kter\u00fd byl zaznamen\u00e1n u jin\u00fdch nukleosid\u016f (de Miranda et al., 1981). EIDD-1931, stejn\u011b jako v\u011bt\u0161ina endogenn\u00edch nukleosid\u016f a xenobiotick\u00fdch analog\u016f nukleosid\u016f, je vysoce pol\u00e1rn\u00ed, hydrofiln\u00ed molekula (cLog P =-2,2), a proto je pravd\u011bpodobn\u00e9, \u017ee k pr\u016fchodu bun\u011b\u010dn\u00fdmi membr\u00e1nami vy\u017eaduje funk\u010dn\u00ed transport\u00e9ry. Tato z\u00e1vislost by vysv\u011btlovala kapacitn\u011b omezen\u00e9 vst\u0159eb\u00e1v\u00e1n\u00ed pozorovan\u00e9 ve farmakokinetick\u00fdch studi\u00edch proveden\u00fdch na my\u0161\u00edch CD-1. D\u0159\u00edv\u011bj\u0161\u00ed zpr\u00e1vy tak\u00e9 nazna\u010dily, \u017ee vychyt\u00e1v\u00e1n\u00ed nukleosid\u016f do my\u0161\u00edch st\u0159evn\u00edch epiteli\u00e1ln\u00edch bun\u011bk je prim\u00e1rn\u011b zprost\u0159edkov\u00e1no koncentra\u010dn\u011b z\u00e1visl\u00fdmi nukleosidov\u00fdmi transport\u00e9ry z\u00e1visl\u00fdmi na sod\u00edku (Cass et al., 1999; Vijayalakshmi a Belt, 1988). 3. 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. 12313-12352 4. de Miranda, P., Krasny, H.C., Page, D.A., Elion, G.B., 1981. Dispozice acikloviru indiferentn\u00edmi druhy. J. Pharmacol. Exp. Ther. 219 (2), 309-315 5. Vijayalakshmi, D., Belt, J.A., 1988. Sodium-dependent nucleoside transport in mouse intestinal epithelial cells (Transport nukleosid\u016f z\u00e1visl\u00fd na sod\u00edku v epiteli\u00e1ln\u00edch bu\u0148k\u00e1ch my\u0161\u00edho st\u0159eva). Dva transportn\u00ed syst\u00e9my s rozd\u00edlnou substr\u00e1tovou specifitou. Biol. Chem. 263 (36), 19419-19423. 6. Yan VC, Khadka S, Arthur K, Ackroyd JJ, Georgiou DK, Muller FL. Pharmacokinetics of Orally Administered GS-441524 in Dogs (Farmakokinetika peror\u00e1ln\u011b pod\u00e1van\u00e9ho GS-441524 u ps\u016f). bioRxiv, doi: https:\/\/doi.org\/10.1101\/2021.02.04.429674 7. https:\/\/ccah.vetmed.ucdavis.edu\/.<\/p>\n","protected":false},"excerpt":{"rendered":"
P\u0159esto\u017ee jsou injekce obecn\u011b pova\u017eov\u00e1ny za spolehliv\u011bj\u0161\u00ed ne\u017e peror\u00e1ln\u00ed forma GS-441524 pro l\u00e9\u010dbu FIP, \u0159ada majitel\u016f ko\u010dek se rozhoduje pro peror\u00e1ln\u00ed variantu, aby se vyhnuli p\u0159\u00edpadn\u00fdm nep\u0159\u00edjemn\u00fdm pocit\u016fm, kter\u00e9 mohou b\u00fdt spojeny s injekcemi. N\u011bkter\u00e9 ko\u010dkovit\u00e9 \u0161elmy mohou po del\u0161\u00ed dob\u011b l\u00e9\u010dby poci\u0165ovat nepohodl\u00ed nebo si vyp\u011bstovat odpor k injekc\u00edm a jsou i takov\u00e9, kter\u00e9 […]<\/p>\n","protected":false},"author":1,"featured_media":22324,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_glsr_average":0,"_glsr_ranking":0,"_glsr_reviews":0,"footnotes":""},"categories":[849],"tags":[],"_links":{"self":[{"href":"https:\/\/fipmed.co\/cs\/wp-json\/wp\/v2\/pages\/22323"}],"collection":[{"href":"https:\/\/fipmed.co\/cs\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/fipmed.co\/cs\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/fipmed.co\/cs\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/fipmed.co\/cs\/wp-json\/wp\/v2\/comments?post=22323"}],"version-history":[{"count":2,"href":"https:\/\/fipmed.co\/cs\/wp-json\/wp\/v2\/pages\/22323\/revisions"}],"predecessor-version":[{"id":29262,"href":"https:\/\/fipmed.co\/cs\/wp-json\/wp\/v2\/pages\/22323\/revisions\/29262"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/fipmed.co\/cs\/wp-json\/wp\/v2\/media\/22324"}],"wp:attachment":[{"href":"https:\/\/fipmed.co\/cs\/wp-json\/wp\/v2\/media?parent=22323"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/fipmed.co\/cs\/wp-json\/wp\/v2\/categories?post=22323"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/fipmed.co\/cs\/wp-json\/wp\/v2\/tags?post=22323"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}