Vitamin D₃ yavlyayetsya aktivnыm antiraxiticheskim faktorom. Samoy vajnoy funktsiyey vitamina D₃ yavlyayetsya regulirovaniye metabolizma kaltsiya i fosfatov, chto sposobstvuyet pravilnoy mineralizatsii i rostu skeleta.

Vitamin D₃ yavlyayetsya yestestvennoy formoy vitamina D, kotoraya obrazuyetsya u cheloveka v koje pod deystviyem solnechnыx luchey. Po sravneniyu s vitaminom D₂ xarakterizuyetsya na 25% boleye vыsokoy aktivnostyu.

Vitamin D svyazыvayetsya so spetsificheskim retseptorom vitamina D (VDR), kotorыy reguliruyet ekspressiyu mnogix genov, vklyuchaya genы ionnogo kanala TRPV6 (obespechivayet absorbtsiyu kaltsiya v kishechnike), CALB1 (kalbindin; obespechivayet transport kaltsiya v krovenosnoye ruslo), BGLAP (osteokaltsin; obespechivayet mineralizatsiyu kostnoy tkani i gomeostaz kaltsiya), SPP1 (osteopontin; reguliruyet migratsiyu osteoklastov), REN (renin; obespechivayet regulyatsiyu AD, yavlyayas klyuchevыm elementom RAAS), IGFBP (svyazыvayuщiy belok insulinopodobnogo faktora rosta; usilivayet deystviye insulinopodobnogo faktora rosta), FGF23 i FGFR23 (faktor rosta fibroblastov 23; reguliruyut urovni kaltsiya, fosfat-aniona, protsessы kletochnogo deleniya fibroblastov), TGFB1 (transformiruyuщiy faktor rosta beta-1; reguliruyet protsessы kletochnogo deleniya i differentsirovki osteotsitov, xondrotsitov, fibroblastov i keratinotsitov), LRP2 (LPNP-retseptor-svyazannыy belok 2; yavlyayetsya posrednikom endotsitoza lipoproteinov nizkoy plotnosti), INSR (retseptor insulina; obespechivayet effektы insulina na lyubыye tipы kletok).

Kolekaltsiferol igrayet suщyestvennuyu rol v absorbtsii kaltsiya i fosfatov v kishechnike, v transporte mineralnыx soley i v protsesse kaltsifikatsii kostey, reguliruyet takje vыvedeniye kaltsiya i fosfatov pochkami.

Kontsentratsiya ionov kaltsiya v krovi obuslovlivayet podderjaniye tonusa mыshts skeletnoy muskulaturы, funktsiyu miokarda, sposobstvuyet provedeniyu nervnogo vozbujdeniya, reguliruyet protsess svertыvaniya krovi.

Nedostatok vitamina D v piщye, narusheniye yego vsasыvaniya, defitsit kaltsiya, a takje nedostatochnoye prebыvaniye na solntse v period bыstrogo rosta rebenka privodit k raxitu, u vzroslыx - k osteomalyatsii, u beremennыx mogut vozniknut simptomы tetanii, narusheniye protsessov obыzvestvleniya kostey novorojdennыx.

Povыshennaya potrebnost v vitamine D voznikayet u jenщin v period menopauzы, poskolku u nix chasto razvivayetsya osteoporoz v svyazi s gormonalnыmi narusheniyami.

Vitamin D obladayet ryadom tak nazыvayemыx vneskeletnыx effektov.

Vitamin D uchastvuyet v funktsionirovanii immunnoy sistemы putem modulyatsii urovney tsitokinov i reguliruyet deleniye limfotsitov T-xelperov i differentsirovku V-limfotsitov. V ryade issledovaniy otmecheno snijeniye zabolevayemosti infektsiyami dыxatelnыx putey na fone priyema vitamina D.

Pokazano, chto vitamin D yavlyayetsya vajnыm zvenom gomeostaza immunnoy sistemы: predotvraщayet autoimmunnыye zabolevaniya (v t.ch. saxarnыy diabet 1 tipa, rasseyannыy skleroz, revmatoidnыy artrit, vospalitelnыye bolezni kishechnika).

Vitamin D obladayet antiproliferativnыm i prodifferentsiruyuщim effektami, kotorыye obuslovlivayut onkoprotektornoye deystviye vitamina D. Otmecheno, chto chastota nekotorыx opuxoley (rak molochnoy jelezы, rak tolstogo kishechnika) povыshayetsya na fone nizkogo urovnya vitamina D v krovi.

Vitamin D uchastvuyet v regulyatsii uglevodnogo i jirovogo metabolizma putem vliyaniya na sintez IRS1 (substrat retseptora insulina 1; uchastvuyet vo vnutrikletochnыx putyax provedeniya signala retseptora insulina), IGF (insulinopodobnыy faktor rosta; reguliruyet balans jirovoy i mыshechnoy tkani), PPAR-δ (aktivirovannыy retseptor proliferatorov peroksisom, tip δ; sposobstvuyet pererabotke izbыtochnogo xolesterina).

Po dannыm epidemiologicheskix issledovaniy defitsit vitamina D assotsiirovan s riskom metabolicheskix narusheniy (metabolicheskiy sindrom i saxarnыy diabet 2 tipa).

Retseptorы i metaboliziruyuщiye fermentы vitamina D ekspressiruyutsya v arterialnыx sosudax, serdtse i prakticheski vo vsex kletkax i tkanyax, imeyuщix otnosheniye k patogenezu serdechno-sosudistыx zabolevaniy. Na jivotnыx modelyax pokazanы antiateroskleroticheskoye deystviye, supressiya renina i preduprejdeniye povrejdeniya miokarda i drugoye. Nizkiye urovni vitamina D u cheloveka svyazanы s neblagopriyatnыmi faktorami riska serdechno-sosudistoy patologii, takimi kak saxarnыy diabet, dislipidemiya, arterialnaya gipertenziya, i assotsiirovanы s riskom serdechno-sosudistыx katastrof, v t.ch. insultov.

V issledovaniyax na eksperimentalnыx modelyax bolezni Altsgeymera pokazano, chto vitamin D₃ snijal nakopleniye amiloida v mozge i uluchshal kognitivnuyu funktsiyu. V neinterventsionnыx issledovaniyax u cheloveka pokazano, chto chastota razvitiya dementsii i bolezni Altsgeymera uvelichivayetsya na fone nizkogo urovnya vitamina D i nizkogo diyetarnogo potrebleniya vitamina D. Otmechalos uxudsheniye kognitivnoy funktsii i zabolevayemosti boleznyu Altsgeymera pri nizkix urovnyax vitamina D.

Vsasыvaniye

Vodnыy rastvor kolekaltsiferola vsasыvayetsya luchshe, chem maslyanыy rastvor (eto imeyet znacheniye pri primenenii u nedonoshennыx detey, t.k. u dannoy kategorii patsiyentov nablyudayetsya nedostatochnost produktsii i postupleniya jelchi v kishechnik, chto narushayet vsasыvaniye vitaminov v vide maslyanыx rastvorov).

Posle priyema vnutr kolekaltsiferol absorbiruyetsya iz tonkoy kishki.

Raspredeleniye i metabolizm

Metaboliziruyetsya v pecheni i pochkax.

Pronikayet cherez platsentarnыy baryer. Vыdelyayetsya s grudnыm molokom. Kolekaltsiferol kumuliruyet v organizme.

Vыvedeniye

T_1/2 kolekaltsiferola iz krovi sostavlyayet neskolko dney. Vыvoditsya pochkami v neznachitelnom kolichestve, bolshaya chast vыvoditsya s jelchyu.

Farmakokinetika v osobыx klinicheskix sluchayax

Pri pochechnoy nedostatochnosti vozmojno uvelicheniye T_1/2.

Profilaktika i lecheniye:

• defitsita vitamina D;
• raxita i raxitopodobnыx zabolevaniy;
• gipokaltsiyemicheskoy tetanii;
• osteomalyatsii;
• zabolevaniya kostey na metabolicheskoy osnove (takix kak gipoparatireoz i psevdogipoparatireoz).

Lecheniye osteoporoza, v t.ch. postmenopauznogo (v sostave kompleksnoy terapii).

Preparat prinimayut vnutr, v 1 lojke jidkosti (1 kaplya soderjit 500 MЕ kolekaltsiferola). Yesli vrach ne naznachil inache, preparat ispolzuyetsya v sleduyuщix dozirovkax:

S tselyu profilaktiki donoshennыm novorojdennыm s 4 nedel jizni do 2-3 let, pri pravilnom uxode i dostatochnom prebыvanii na svejem vozduxe, preparat naznachayut v doze 500 MЕ (1 kaplya)/sut.

Nedonoshennыm detyam s 4 nedel jizni, bliznetsam i detyam, jivuщim v neblagopriyatnыx usloviyax, naznachayut 1000-1500 MЕ (2-3 kapli)/sut.

V letneye vremya goda dozu mojno umenshit do 500 MЕ (1 kaplya)/sut.

Vzroslыm zdorovыm litsam bez narusheniy vsasыvaniya - 500 MЕ (1 kaplya)/sut; vzroslыm patsiyentam pri sindrome malabsorbtsii - 3000-5000 MЕ (6-10 kapel)/sut.

Beremennыm jenщinam yejednevno naznachayut 500 MЕ (1 kaplya)/sut v techeniye vsey beremennosti, ili 1000 MЕ (2 kapli)/sut, nachinaya s 28 nedeli beremennosti.

V postmenopauznom periode naznachayut 500-1000 MЕ (1-2 kapli)/sut.

S tselyu lecheniya pri raxite preparat naznachayut yejednevno v doze 1000-5000 MЕ (2-10 kapel)/sut v techeniye 4-6 nedel v zavisimosti ot stepeni tyajesti raxita (I, II ili III) i varianta techeniya zabolevaniya. Pri etom sleduyet kontrolirovat klinicheskoye sostoyaniye patsiyenta i bioximicheskiye pokazateli (uroven kaltsiya, fosfora, aktivnost ЩF v krovi i v moche). Nachalnaya doza sostavlyayet 1000 MЕ/sut v techeniye 3-5 dney, zatem pri xoroshey perenosimosti dozu povыshayut do individualnoy lechebnoy (obыchno do 3000 MЕ/sut). Doza 5000 MЕ/sut naznachayetsya tolko pri vыrajennыx kostnыx izmeneniyax.

Pri neobxodimosti posle 1 nedeli pererыva kurs lecheniya mojno povtorit.

Lecheniye sleduyet prodoljat do polucheniya chetkogo lechebnogo effekta, s posleduyuщim perexodom na profilakticheskuyu dozu 500-1500 MЕ/sut.

Pri lechenii raxitopodobnыx zabolevaniy naznachayut 20 000-30 000 MЕ (40-60 kapel)/sut v zavisimosti ot vozrasta, massы tela i tyajesti zabolevaniy, pod kontrolem bioximicheskix pokazateley krovi i analiza mochi. Kurs lecheniya - 4-6 nedel. Lecheniye provodyat pod kontrolem vracha.

Pri lechenii postmenopauznogo osteoporoza (v sostave kompleksnoy terapii) naznachayut 500-1000 MЕ (1-2 kapli)/sut.

Dozu ustanavlivayut individualno, s uchetom kolichestva vitamina D, postupayuщyego s piщyey.

Simptomы gipervitaminoza D: poterya appetita, toshnota, rvota; golovnыye, mыshechnыye i sustavnыye boli; zaporы; suxost v polosti rta; poliuriya; slabost; narusheniye psixiki, v t.ch. depressiya; poterya massы tela; narusheniye sna; povыsheniye temperaturы; v moche poyavlyayetsya belok, leykotsitы, gialinovыye tsilindrы; povыsheniye urovnya kaltsiya v krovi i yego vыdeleniye s mochoy; vozmojen kaltsinoz pochek, krovenosnыx sosudov, legkix. Pri poyavlenii priznakov gipervitaminoza D neobxodimo otmenit preparat, ogranichit postupleniye kaltsiya, naznachit vitaminы A, S i V.

Prochiye: vozmojnы reaktsii povыshennoy chuvstvitelnosti.

• gipervitaminoz D;
• giperkaltsiyemiya;
• giperkaltsiuriya;
• mochekamennaya bolezn (obrazovaniye kaltsiyevыx oksalatnыx kamney v pochkax);
• sarkoidoz;
• ostrыye i xronicheskiye zabolevaniya pecheni i pochek;
• pochechnaya nedostatochnost;
• aktivnaya forma tuberkuleza legkix;
• povыshennaya chuvstvitelnost k komponentam preparata (osobenno k benzilovomu spirtu).

S ostorojnostyu sleduyet primenyat preparat u patsiyentov v sostoyanii immobilizatsii; pri priyeme tiazidov, serdechnыx glikozidov (osobenno glikozidov naperstyanki); pri beremennosti i v period laktatsii (grudnogo vskarmlivaniya); u grudnыx detey pri predraspolojennosti k rannemu zarastaniyu rodnichkov (kogda ot rojdeniya ustanovlenы malыye razmerы perednego rodnichka).

Protivoepilepticheskiye sredstva, rifampitsin, kolestiramin snijayut reabsorbtsiyu vitamina D₃.

Primeneniye odnovremenno s tiazidnыmi diuretikami povыshayet risk proyavleniya giperkaltsiyemii.

Odnovremennoye primeneniye s serdechnыmi glikozidami mojet usilivat ix toksicheskoye deystviye (povыshayetsya risk proyavleniya narusheniy ritma serdtsa).

Sleduyet izbegat peredozirovki.

Individualnoye obespecheniye opredelennoy potrebnosti doljno uchitыvat vse vozmojnыye istochniki etogo vitamina.

Slishkom vыsokiye dozы vitamina D₃, primenyayemыye prodoljitelno, ili udarnыye dozы mogut bыt prichinoy xronicheskogo gipervitaminoza D₃.

Opredeleniye sutochnoy potrebnosti rebenka v vitamine D i sposoba yego primeneniya doljno ustanavlivatsya vrachom individualno i kajdыy raz podvergatsya korrektsii vo vremya periodichnыx obsledovaniy, osobenno v pervыye mesyatsы jizni.

Pri dostijenii adekvatnogo urovnya kontsentratsii vitamina D v krovi (>30 ng/ml 25(ON)D) u vzroslыx vozmojno prodoljeniye podderjivayuщyey terapii preparatom Akvadetrim^® v doze 1500–2000 MЕ (3-4 kapli)/sut.

Ne primenyat odnovremenno s vitaminom D₃ vыsokix doz kaltsiya.

Vo vremya lecheniya neobxodim periodicheskiy kontrol kontsentratsii fosfatov v krovi i moche.

Pri dlitelnom priyeme kolekaltsiferola neobxodimo regulyarno opredelyat uroven kaltsiya v sыvorotke krovi i moche, a takje otsenivat funktsiyu pochek putem izmereniya sыvorotochnogo urovnya kreatinina. Pri neobxodimosti, sleduyet korrektirovat dozu kolekaltsiferola v zavisimosti ot urovnya kaltsiya v sыvorotke krovi.

Pri beremennosti ne sleduyet primenyat vitamin D₃ v vыsokix dozax iz-za vozmojnosti proyavleniya teratogennogo deystviya v sluchaye peredozirovki.

S ostorojnostyu sleduyet naznachat vitamin D₃ v period laktatsii, t.k. pri primenenii preparata v vыsokix dozax u kormyaщyey materi vozmojno razvitiye simptomov peredozirovki u rebenka.

Preparat sleduyet xranit v originalnoy upakovke v nedostupnom dlya detey meste pri temperature ne vыshe 25°C.

Simptomы: snijeniye appetita, toshnota, rvota, zapor, bespokoystvo, jajda, poliuriya, diareya, kishechnaya kolika. Chastыmi simptomami yavlyayutsya golovnaya, mыshechnaya i sustavnaya boli, narusheniya psixiki, v t.ch. depressiya, ataksiya, stupor, progressiruyuщaya poterya massы tela. Razvivayetsya narusheniye funktsii pochek s albuminuriyey, eritrotsituriyey i poliuriyey, povыshennoy poterey kaliya, gipostenuriyey, nikturiyey i povыsheniyem AD.

V tyajelыx sluchayax vozmojno pomutneniye rogovitsы, reje - otek sosochka zritelnogo nerva, vospaleniye radujnoy obolochki vplot do razvitiya kataraktы. Vozmojno obrazovaniye kamney v pochkax, kaltsifikatsiya myagkix tkaney, v t.ch. krovenosnыx sosudov, serdtsa, legkix, koji.

Redko razvivayetsya xolestaticheskaya jeltuxa.

Lecheniye: otmena preparata. Naznachayut priyem bolshogo kolichestva jidkosti. Pri neobxodimosti mojet potrebovatsya gospitalizatsiya.