{"id":1441,"date":"2025-09-27T09:45:11","date_gmt":"2025-09-27T09:45:11","guid":{"rendered":"https:\/\/medi-pharm.sk\/od-racematu-k-jednemu-enantiomeru"},"modified":"2025-10-25T08:55:14","modified_gmt":"2025-10-25T08:55:14","slug":"od-racematu-k-jednemu-enantiomeru","status":"publish","type":"post","link":"https:\/\/medi-pharm.sk\/sk\/od-racematu-k-jednemu-enantiomeru","title":{"rendered":"Od racem\u00e1tu k jedn\u00e9mu enantiom\u00e9ru"},"content":{"rendered":"\t\t<div data-elementor-type=\"wp-post\" data-elementor-id=\"1441\" class=\"elementor elementor-1441 elementor-791\" data-elementor-post-type=\"post\">\n\t\t\t\t<div class=\"elementor-element elementor-element-463e71ad e-flex e-con-boxed e-con e-parent\" data-id=\"463e71ad\" data-element_type=\"container\">\n\t\t\t\t\t<div class=\"e-con-inner\">\n\t\t\t\t<div class=\"elementor-element elementor-element-19ee974 elementor-widget elementor-widget-spacer\" data-id=\"19ee974\" data-element_type=\"widget\" data-widget_type=\"spacer.default\">\n\t\t\t\t\t\t\t<div class=\"elementor-spacer\">\n\t\t\t<div class=\"elementor-spacer-inner\"><\/div>\n\t\t<\/div>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-15175f2d elementor-widget elementor-widget-theme-post-title elementor-page-title elementor-widget-heading\" data-id=\"15175f2d\" data-element_type=\"widget\" data-widget_type=\"theme-post-title.default\">\n\t\t\t\t\t<h3 class=\"elementor-heading-title elementor-size-default\">Od racem\u00e1tu k jedn\u00e9mu enantiom\u00e9ru<\/h3>\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-3ea78ed0 elementor-widget elementor-widget-text-editor\" data-id=\"3ea78ed0\" data-element_type=\"widget\" data-widget_type=\"text-editor.default\">\n\t\t\t\t\t\t\t\t\t<p><strong>Farmakokinetick\u00e9 rozdiely, klinick\u00fd kontext a procesn\u00e1 expert\u00edza MediPharm<\/strong><\/p><p><br>\u017dal\u00fado\u010dn\u00e1 kyselina je u\u017e dlho uzn\u00e1van\u00e1 ako k\u013e\u00fa\u010dov\u00fd faktor vo fyziol\u00f3gii hornej \u010dasti gastrointestin\u00e1lneho traktu, pri\u010dom zohr\u00e1va z\u00e1sadn\u00fa \u00falohu pri tr\u00e1ven\u00ed bielkov\u00edn, absorpcii miner\u00e1lov a do ur\u010ditej miery poskytuje prirodzen\u00fa obranu proti bakteri\u00e1lnym infekci\u00e1m. Nevhodn\u00e9 hladiny \u017eal\u00fado\u010dnej kyseliny v\u0161ak sp\u00f4sobuj\u00fa nieko\u013eko roz\u0161\u00edren\u00fdch patol\u00f3gi\u00ed, vr\u00e1tane gastroezofage\u00e1lnej refluxnej choroby a peptick\u00fdch vredov, ktor\u00e9 sp\u00f4sobuj\u00fa boles\u0165 a utrpenie mili\u00f3nom \u013eud\u00ed a e\u0161te pred p\u00e1r desa\u0165ro\u010diami mohli by\u0165 \u017eivot ohrozuj\u00face, ak sa nelie\u010dili. Mo\u017enosti lie\u010dby boli vtedy v\u0161ak obmedzen\u00e9. Napr\u00edklad pri peptick\u00fdch vredoch bola hlavnou lie\u010dbou aplik\u00e1cia antac\u00edd na neutraliz\u00e1ciu prebyto\u010dnej \u017eal\u00fado\u010dnej kyseliny, ale to poskytovalo len do\u010dasn\u00fa \u00fa\u013eavu. Alternat\u00edvou bola oper\u00e1cia, ktor\u00e1 v\u0161ak mohla ma\u0165 v\u00e1\u017ene ved\u013eaj\u0161ie \u00fa\u010dinky. Farmakologick\u00e1 kontrola komplexn\u00e9ho mechanizmu sekr\u00e9cie \u017eal\u00fado\u010dnej kyseliny bola preto dlho \u017eiaduca.     <\/p><p>V nasleduj\u00facich desa\u0165ro\u010diach sa farmakologick\u00e9 strat\u00e9gie vyv\u00edjali od jednoduchej neutraliz\u00e1cie kyseliny k inhib\u00edcii samotnej sekr\u00e9cie kyseliny, najprv prostredn\u00edctvom antagonistov histam\u00ednov\u00fdch H\u2082-receptorov, ktor\u00e9 zni\u017eovali produkciu kyseliny blokovan\u00edm aktivity pariet\u00e1lnych buniek stimulovanej histam\u00ednom, potom prostredn\u00edctvom objavenia a v\u00fdvoja inhib\u00edtorov prot\u00f3novej pumpy, ktor\u00e9 poskytovali ove\u013ea silnej\u0161iu a dlhodobej\u0161iu supresiu sekr\u00e9cie \u017eal\u00fado\u010dnej kyseliny. Omeprazol, hlavn\u00fd liek tejto skupiny, sa uk\u00e1zal ako v\u00fdrazne lep\u0161\u00ed v porovnan\u00ed s predch\u00e1dzaj\u00facimi lie\u010debn\u00fdmi re\u017eimami antagonistov H\u2082-receptorov u pacientov s <\/p><p>dvan\u00e1stnikov\u00fdmi a \u017eal\u00fado\u010dn\u00fdmi vredmi. Na z\u00e1klade t\u00fdchto objavov bol omeprazol uveden\u00fd ako lie\u010dba prvej vo\u013eby pre spom\u00ednan\u00e9 ochorenia v Eur\u00f3pe v roku 1988. <\/p><p>Esomeprazol, S-izom\u00e9r omeprazolu, bol uveden\u00fd na trh spolo\u010dnos\u0165ou AstraZeneca v roku 2001 pod obchodn\u00fdm n\u00e1zvom Nexium, kr\u00e1tko pred vypr\u0161an\u00edm patentu omeprazolu.<\/p><p>Omeprazol obsahuje chir\u00e1lny at\u00f3m s\u00edry v sulfoxidovej skupine, \u010do vedie k vzniku dvoch optick\u00fdch izom\u00e9rov, R- a S-formy. Esomeprazol predstavuje opticky \u010dist\u00fd S-enantiom\u00e9r, ktor\u00fd bol vyvinut\u00fd s od\u00f4vodnen\u00edm, \u017ee jeho farmakokinetick\u00fd profil by mohol pon\u00faknu\u0165 v\u00e4\u010d\u0161iu klinick\u00fa konzistenciu medzi jednotlivcami. Chir\u00e1lny prechod na esomeprazol bol dosiahnut\u00fd vyvinut\u00edm enantioselekt\u00edvnej synt\u00e9zy, ktor\u00e1 priamo produkuje S-enantiom\u00e9r, namiesto jeho odde\u013eovania z hotov\u00e9ho racem\u00e1tu.  <\/p><p>Hoci oba enantiom\u00e9ry zdie\u013eaj\u00fa identick\u00fd mechanizmus \u00fa\u010dinku, t.j. ireverzibiln\u00fa inhib\u00edciu H\u207a\/K\u207a-ATP\u00e1zy v \u017eal\u00fado\u010dn\u00fdch pariet\u00e1lnych bunk\u00e1ch, rozdiely vznikaj\u00fa v ich hepat\u00e1lnom metabolizme, najm\u00e4 v ich afinite k cytochr\u00f3mu P450 2C19 (CYP2C19).<\/p><p>CYP2C19 je zodpovedn\u00fd za oxidat\u00edvny metabolizmus inhib\u00edtorov prot\u00f3novej pumpy. Genetick\u00e9 vari\u00e1cie tohto enz\u00fdmu ved\u00fa k dvom odli\u0161n\u00fdm fenotypom metaboliz\u00e1torov, a to slab\u00fdm a extenz\u00edvnym, \u010do sp\u00f4sobuje variabiln\u00e9 plazmatick\u00e9 hladiny lieku. Esomeprazol vykazuje zn\u00ed\u017een\u00fa metabolick\u00fa clearance prostredn\u00edctvom CYP2C19 v porovnan\u00ed s jeho R-formou, \u010do vedie k vy\u0161\u0161ej syst\u00e9movej biologickej dostupnosti, stabilnej\u0161\u00edm plazmatick\u00fdm koncentr\u00e1ci\u00e1m a niekedy k pred\u013a\u017eenej supresii kyseliny. Tieto rozdiely boli hlavn\u00fdm farmakokinetick\u00fdm od\u00f4vodnen\u00edm pre formul\u00e1ciu s jedn\u00fdm enantiom\u00e9tom.   <\/p><p>Porovn\u00e1vacie klinick\u00e9 \u00fadaje v\u0161ak ukazuj\u00fa, \u017ee rozsah terapeutick\u00e9ho zlep\u0161enia zost\u00e1va v\u00e4\u010d\u0161inou mierny. V praxi mo\u017eno prechod z omeprazolu na esomeprazol vn\u00edma\u0165 sk\u00f4r ako inkrement\u00e1lnu optimaliz\u00e1ciu ne\u017e ako prelomov\u00fa terapeutick\u00fa inov\u00e1ciu. Zatia\u013e \u010do esomeprazol pon\u00faka zn\u00ed\u017een\u00fa interindividu\u00e1lnu farmakokinetick\u00fa variabilitu a potenci\u00e1lne predv\u00eddate\u013enej\u0161iu kontrolu kyseliny, obe zl\u00fa\u010deniny zost\u00e1vaj\u00fa terapeuticky porovnate\u013en\u00e9 pri pou\u017eit\u00ed vo farmakologicky ekvivalentn\u00fdch d\u00e1vkach. V d\u00f4sledku toho sa vedeck\u00e9 od\u00f4vodnenie chir\u00e1lneho prechodu opiera prim\u00e1rne o vylep\u0161enie formul\u00e1cie a farmakokinetick\u00fa stabiliz\u00e1ciu, sk\u00f4r ne\u017e o rozdiely vo farmakodynamike alebo klinickej \u00fa\u010dinnosti.   <\/p><p>Prechod omeprazol-esomeprazol ilustruje, ako m\u00f4\u017ee presn\u00e1 kontrola optimaliz\u00e1cie procesu vies\u0165 k zmyslupln\u00fdm, hoci niekedy len inkrement\u00e1lnym zlep\u0161eniam. Odbornos\u0165 spolo\u010dnosti MediPharm v oblasti GMP v\u00fdroby, lyofiliz\u00e1cie a v\u00fdvoja formul\u00e1ci\u00ed poskytuje ide\u00e1lny z\u00e1klad pre v\u00fdrobu formul\u00e1ci\u00ed na b\u00e1ze prazolov a podporu podobn\u00fdch inova\u010dn\u00fdch projektov v spolupr\u00e1ci s priemyseln\u00fdmi partnermi. <\/p><p><strong>Zdroje:<\/strong><\/p><p>[1] Pi\u00f1eiro, F.J. a Rogelio Alberto, F.A. (2022) &#8218;Pr\u00edpadov\u00e1 \u0161t\u00fadia chir\u00e1lnej strat\u00e9gie prechodu AstraZeneca z Omeprazolu na Esomeprazol&#8216;, Generics and Biosimilars Initiative Journal, 11(2), s. 57\u201364. doi:10.5639\/gabij.2022.1102.011. <\/p><p>[2] Olbe, L., Carlsson, E. a Lindberg, P. (2003) &#8218;Exped\u00edcia inhib\u00edtorov prot\u00f3novej pumpy: Pr\u00edpadov\u00e9 hist\u00f3rie omeprazolu a esomeprazolu&#8216;, Nature Reviews Drug Discovery, 2(2), s. 132\u2013139. doi:10.1038\/nrd1010. <\/p>\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-65278e31 elementor-widget elementor-widget-spacer\" data-id=\"65278e31\" data-element_type=\"widget\" data-widget_type=\"spacer.default\">\n\t\t\t\t\t\t\t<div class=\"elementor-spacer\">\n\t\t\t<div class=\"elementor-spacer-inner\"><\/div>\n\t\t<\/div>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-4ab36867 elementor-widget elementor-widget-post-info\" data-id=\"4ab36867\" data-element_type=\"widget\" data-widget_type=\"post-info.default\">\n\t\t\t\t\t\t\t<ul class=\"elementor-inline-items elementor-icon-list-items elementor-post-info\">\n\t\t\t\t\t\t\t\t<li class=\"elementor-icon-list-item elementor-repeater-item-947b1e1 elementor-inline-item\" itemprop=\"datePublished\">\n\t\t\t\t\t\t<a href=\"https:\/\/medi-pharm.sk\/sk\/2025\/09\/27\">\n\t\t\t\t\t\t\t\t\t\t\t<span class=\"elementor-icon-list-icon\">\n\t\t\t\t\t\t\t\t<svg aria-hidden=\"true\" class=\"e-font-icon-svg e-fas-calendar\" viewBox=\"0 0 448 512\" xmlns=\"http:\/\/www.w3.org\/2000\/svg\"><path d=\"M12 192h424c6.6 0 12 5.4 12 12v260c0 26.5-21.5 48-48 48H48c-26.5 0-48-21.5-48-48V204c0-6.6 5.4-12 12-12zm436-44v-36c0-26.5-21.5-48-48-48h-48V12c0-6.6-5.4-12-12-12h-40c-6.6 0-12 5.4-12 12v52H160V12c0-6.6-5.4-12-12-12h-40c-6.6 0-12 5.4-12 12v52H48C21.5 64 0 85.5 0 112v36c0 6.6 5.4 12 12 12h424c6.6 0 12-5.4 12-12z\"><\/path><\/svg>\t\t\t\t\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t<span class=\"elementor-icon-list-text elementor-post-info__item elementor-post-info__item--type-date\">\n\t\t\t\t\t\t\t\t\t\t<time>27 septembra, 2025<\/time>\t\t\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t<\/a>\n\t\t\t\t<\/li>\n\t\t\t\t<li class=\"elementor-icon-list-item elementor-repeater-item-f958ce5 elementor-inline-item\">\n\t\t\t\t\t\t\t\t\t\t<span class=\"elementor-icon-list-icon\">\n\t\t\t\t\t\t\t\t<svg aria-hidden=\"true\" class=\"e-font-icon-svg e-far-clock\" viewBox=\"0 0 512 512\" xmlns=\"http:\/\/www.w3.org\/2000\/svg\"><path d=\"M256 8C119 8 8 119 8 256s111 248 248 248 248-111 248-248S393 8 256 8zm0 448c-110.5 0-200-89.5-200-200S145.5 56 256 56s200 89.5 200 200-89.5 200-200 200zm61.8-104.4l-84.9-61.7c-3.1-2.3-4.9-5.9-4.9-9.7V116c0-6.6 5.4-12 12-12h32c6.6 0 12 5.4 12 12v141.7l66.8 48.6c5.4 3.9 6.5 11.4 2.6 16.8L334.6 349c-3.9 5.3-11.4 6.5-16.8 2.6z\"><\/path><\/svg>\t\t\t\t\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t<span class=\"elementor-icon-list-text elementor-post-info__item elementor-post-info__item--type-time\">\n\t\t\t\t\t\t\t\t\t\t<time>9:45 am<\/time>\t\t\t\t\t<\/span>\n\t\t\t\t\t\t\t\t<\/li>\n\t\t\t\t<\/ul>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-7d3a285b elementor-widget elementor-widget-spacer\" data-id=\"7d3a285b\" data-element_type=\"widget\" data-widget_type=\"spacer.default\">\n\t\t\t\t\t\t\t<div class=\"elementor-spacer\">\n\t\t\t<div class=\"elementor-spacer-inner\"><\/div>\n\t\t<\/div>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t<div class=\"elementor-element elementor-element-73f9eb8 e-flex e-con-boxed e-con e-parent\" data-id=\"73f9eb8\" data-element_type=\"container\">\n\t\t\t\t\t<div class=\"e-con-inner\">\n\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t","protected":false},"excerpt":{"rendered":"<p>Farmakokinetick\u00e9 rozdiely, klinick\u00fd kontext a procesn\u00e1 expert\u00edza MediPharm \u017dal\u00fado\u010dn\u00e1 kyselina je u\u017e dlho uzn\u00e1van\u00e1 ako k\u013e\u00fa\u010dov\u00fd faktor vo fyziol\u00f3gii hornej \u010dasti gastrointestin\u00e1lneho traktu, pri\u010dom zohr\u00e1va z\u00e1sadn\u00fa \u00falohu pri tr\u00e1ven\u00ed bielkov\u00edn, absorpcii miner\u00e1lov a do ur\u010ditej miery poskytuje prirodzen\u00fa obranu proti bakteri\u00e1lnym infekci\u00e1m. Nevhodn\u00e9 hladiny \u017eal\u00fado\u010dnej kyseliny v\u0161ak sp\u00f4sobuj\u00fa nieko\u013eko roz\u0161\u00edren\u00fdch patol\u00f3gi\u00ed, vr\u00e1tane gastroezofage\u00e1lnej refluxnej choroby [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":1442,"comment_status":"closed","ping_status":"open","sticky":false,"template":"elementor_header_footer","format":"standard","meta":{"footnotes":""},"categories":[15],"tags":[],"class_list":["post-1441","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-uncategorized-sk"],"_links":{"self":[{"href":"https:\/\/medi-pharm.sk\/sk\/wp-json\/wp\/v2\/posts\/1441","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/medi-pharm.sk\/sk\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/medi-pharm.sk\/sk\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/medi-pharm.sk\/sk\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/medi-pharm.sk\/sk\/wp-json\/wp\/v2\/comments?post=1441"}],"version-history":[{"count":3,"href":"https:\/\/medi-pharm.sk\/sk\/wp-json\/wp\/v2\/posts\/1441\/revisions"}],"predecessor-version":[{"id":1445,"href":"https:\/\/medi-pharm.sk\/sk\/wp-json\/wp\/v2\/posts\/1441\/revisions\/1445"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/medi-pharm.sk\/sk\/wp-json\/wp\/v2\/media\/1442"}],"wp:attachment":[{"href":"https:\/\/medi-pharm.sk\/sk\/wp-json\/wp\/v2\/media?parent=1441"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/medi-pharm.sk\/sk\/wp-json\/wp\/v2\/categories?post=1441"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/medi-pharm.sk\/sk\/wp-json\/wp\/v2\/tags?post=1441"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}