Antidiabetesic Dapagliflozin

Uhlu lwezidakamizwa ezilwa nesifo sikashukela emakhemisi (kanye nezithasiselo zokudla, itiye le-herbal, amavithamini), ukunikezwa kwemithi kanye nokungabhali, kuyamangaza. Futhi nokho, izidakamizwa ezintsha, ngokokuhlola, ziveze imiphumela ekholisayo. Omunye wale mishanguzo, osuvele wazijwayela kwabanesifo sikashukela, yiForsiga esekwe dapagliflozin.

Ukwakheka kwomuthi kanye nendlela yokukhululwa

Kwinethiwekhi yamakhemisi, iDapagliflozin ithengiswa njengamathebulethi aphuzi. Ngokuya ngobuningi, ayindilinga futhi anele ukumaka “5” ngaphambili kanye no- “1427” ngakolunye uhlangothi, noma abunjwe ngamadayimane anomaki “10” no “1428” ngokulandelana.

Epuletini elilodwa kumaseli abeke ama-10 ama-pcs. amaphilisi. Kukhodi ngayinye yamakhadibhodi kungabekwa amapuleti amathathu noma ama-9. Kunamashini nezingcezu eziyi-14 inye. Ebhokisini lamapuleti anjalo ungathola amabili noma amane.

Impilo yeshalofu yemithi iyiminyaka emi-3. Kwi-dapagliflozin, intengo eketheni likhemisi isuka kuma-ruble angama-2497.

Isakhi esisebenzayo somuthi yi-dapagliflozin. Ngaphezu kwalokho, kusetshenziswa ama-fillers: i-cellulose, i-lactose eyomile, i-silicon dioxide, i-crospovidone, i-magnesium stearate.

Ikhemisi

Isithako esisebenzayo, i-dapagliflozin, iyi-inhibitor enamandla (i-SGLT2) yencazelo ye-2 glucose transporter. Ukuchazwa ezinso, akuveli kwezinye izitho nezicubu (izinhlobo ezingama-70 ezihloliwe). I-SGLT2 iyisiphathi esikhulu esiyingxenye yokubuyiselwa kwe-glucose.

Le nqubo ayeki ngesifo sikashukela sohlobo 2, kungakhathalekile ukuba ne-hyperglycemia. Ngokuvimbela ukudluliselwa kweshukela, i-inhibitor yehlisa ukuphinda ibuyele ezinsweni futhi iyadedelwa. Ngenxa yalokhu kuhlangana, ushukela uyancipha - kokubili esiswini esingenalutho nangemva kokuvivinya umzimba, amanani entengo we-glycosylated hemoglobin ayathuthuka.

Inani ushukela asuswe kuncike enanini likashukela ngokweqile kanye nesilinganiso sokuhlunga kwe-glomerular. I-inhibitor ayithinti ukukhiqizwa kwendalo kweglucose yakho yemvelo. Amandla ayo azimele ekukhiqizeni i-insulin kanye nezinga lokuzwela kuyo.

Ukuhlolwa ngalo muthi kuqinisekisile ukuthuthuka kwesimo sama-b-cell abhekene nokuhlanganiswa kwe-insulin yemvelo.

Isithelo se-glucose ngale ndlela kuthuthukisa ukusetshenziswa kwekalori nokulahleka kwesisindo ngokweqile, kunomphumela omncane wokuguguleka.

Umuthi awuthinti abanye abahambisa ushukela abasabalalisa emzimbeni wonke. Ku-SGLT2, i-dapagliflozin ikhombisa ukukhethwa okuphindwe izikhathi eziyi-1,400 kune-SGLT1 ebambisene nayo, ebhekele ukufakwa kwe-glucose emathunjini.

I-Pharmacodynamics

Ngokusetshenziswa kweForigi ngabanesifo sikashukela kanye nababambiqhaza abanempilo ekuhlolweni, ukwanda komphumela we-glucosuric kwaphawulwa. Ngokwezibalo ezithile, kubukeka kanjena: emavikini ayi-12, abanesifo sikashukela baphuze umuthi nge-10 gm / ngosuku. Ngalesi sikhathi sesikhathi, izinso zasusa kufinyelela ku-70 g we-glucose, enele ku-280 kcal / ngosuku.

Ukwelashwa kwe-Dapagliflozin kuhambisane ne-osmotic diuresis. Ngerejimeni yokwelashwa echaziwe, umphumela we-diuric awushintshiwe amasonto ayi-12 futhi waba ngama-375 ml / ngosuku. Le nqubo yayihambisana nokufakelwa kwenani elincane le-sodium, kepha lokhu akuthinti okuqukethwe kwalo osegazini.

I-Pharmacokinetics

1. Ukuhlelwa. Ngokusetshenziswa komlomo, umuthi udonswa egazini lokugaya ukudla ngokushesha futhi ucishe ube yi-100%. Ukudla okwanele akukuthinti imiphumela yokufakwa emzimbeni. Ukuqongelelwa kwesiqalo somuthi osegazini kubonwa ngemuva kwamahora ama-2 lapho kusetshenziswa esiswini esingenalutho. Lapho umthamo umuthi uphakeme, uyanda kakhulu emgudwini weplasma isikhathi esithile. Ngokwesilinganiso se-10 mg / ngosuku. ngokuphelele bioavailability kuzoba cishe 78%. Kubabambiqhaza abanempilo ekuhlolweni, ukudla akubanga nomthelela obalulekile emtholampilo wesidakamizwa.
2. Ukusatshalaliswa. Imithi ibopha amaprotheni egazi ngokwesilinganiso sama-91%. Ngezifo ezikhona, ngokwesibonelo, ukwehluleka kwezinso, le nkomba ihleli.
3. Ukukhohlisa umzimba. I-TЅ kubantu abaphilile amahora angama-12,0 ngemuva komthamo owodwa wethebhulethi enesisindo esingu-10 mg. I-Dapagliflozin iguqulwa ibe yi-inert metabolite ye-dapagliflozin-3-O-glucuronide, engenamphumela we-pharmacological
4. Ukuzala. Umuthi onama-metabolites uphuma ngosizo lwezinso ngesimo salo sokuqala. Cishe ama-75% akhishwa umchamo, amanye asemathunjini. Cishe i-15% ye-dapagliflozin iphuma ifomu elimsulwa.

Amacala akhethekile

Inani le-glucose izinso elichichima ekuphazamiseni ukusebenza kwazo lincike ekujuleni kwenhliziyo. Ngezitho ezinempilo, le nkomba ingu-85 g, enefomu elikhanyayo - 52 g, enesilinganiso - 18 g, ezimweni ezinzima - i-11 g ye-glucose. I-inhibitor ibopha amaprotheni ngendlela efanayo kwababili abanesifo sikashukela naseqenjini elilawulayo. Imiphumela ye-hemodialysis emiphumeleni yokwelashwa ayifundwanga.

Ngezindlela eziphansi nezilinganiselwe zokungasebenzi kahle kwesibindi, ama-pharmacokinetics eCmax ne-AUC ahluka ngo-12% no-36%. Iphutha elinjalo alidlali indima yomtholampilo, ngakho-ke, asikho isidingo sokwehlisa umthamo walesi sigaba sikashukela. Ngefomu elinzima, lezi zinkomba ziyehluka ku-40% no-67%.

Ebusheni obukhulu, ushintsho olukhulu ekuvezweni kwalo muthi alubhekwanga (uma kungekho zici ezithile ezenza isithombe somtholampilo). Lapho buthakathaka izinso, kuphakama ukuvezwa kwe-dapagliflozin.

Isesimweni esizinzile, ezigulini ezinesifo sikashukela sohlobo 2, i-Cmax esezingeni eliphansi ne-AUC ziphakeme kunamadoda anesifo sikashukela ngama-22%.

Umehluko emiphumeleni ngokuya ngokuba ngowomjaho waseYurophu, Negroid noma Mongoloid awutholakalanga.

Ngokwesisindo ngokweqile, izinkomba eziphansi kakhulu zomphumela womuthi ziyaqoshwa, kepha amaphutha anjalo awabalulekile ngokomtholampilo, adinga ukulungiswa komthamo.

Ngubani olusizo nge-forsyga

Lapho ushintsha indlela yokuphila (ukudla okune-carb ephansi, umthwalo owanele wemisipha), ukwenza i-glycemia ifane, umuthi uyasetshenziswa:

• Nge-monotherapy;
• Ngokuhambisana ne-metformin (uma umphumela we-hypoglycemic unganele);
• Kwisekethe yokuqala ehlanganisiwe.

Contraindication

• Ukuzwela okuphezulu kwizithako zefomula;
• Uhlobo 1 sikashukela;
• I-ketoacidosis;
• Isifo sezinso esiqinile;
• Ukungabekezelelani kofuzo kushukela kanye ne-lactase;
• Ukukhulelwa nokukhulelwa;
• Izingane nentsha (ayikho idatha ethembekile);
• Ngemuva kokugula kakhulu, okuhambisana nokulahleka kwegazi;
• Iminyaka enguSenile (kusuka eminyakeni engama-75) - njengomuthi wokuqala.

Izinhlelo ezijwayelekile zokusebenzisa

I-algorithm yokwelashwa kwe-dapagliflozin ingudokotela, kepha imiyalo ejwayelekile inikezwe emiyalweni yokusetshenziswa.

1. I-Monotherapy. Ukwemukelwa akuxhomeki ekudleni, okujwayelekile nsuku zonke ngu-10 mg ngasikhathi.
2. Ukwelashwa okuphelele. Ngokuhlanganiswa ne-metformin - 10 mg / usuku.
3. Isikimu sokuqala. Ngokwesilinganiso seMetformin 500 mg / ngosuku. I-Forsigu thatha ithebhu eyi-1. (10g) ngosuku. Uma umphumela oyifunayo ungekho, khuphula isilinganiso seMetformin.
4. Ngama-hepatic pathologies. Abantu abanesifo sikashukela abanobunzima besibindi besesilinganisweni abadingi ukulungiswa kwamthamo. Ngefomu elinzima, baqala nge-5 g / ngosuku .. Ngokuphendula okujwayelekile komzimba, okujwayelekile kungandiswa ku-10 mg / ngosuku.
5. Ngokuphatheka kabi kwezinso. Ngefomu elinganisela nelinzima, i-Forsig ayinqunyelwe (lapho imvume ye-creatinine (CC) <60 ml / min.);
6. Ukuguga. Lapho usumdala, lapho ukhetha uhlobo lokwelashwa, aqondiswa umthamo wegazi kanye nesimo sezinso.

Imiphumela emibi

Izifundo zokuphepha zomuthi bezibandakanya izisebenzi zokuzithandela eziyi-1,193 ezinikezwe i-Fortigu nge-10 mg / ngosuku, kanye nabahlanganyeli be-1393 abathathe i-placebo. Imvamisa yemiphumela engathandeki icishe ifane.

Phakathi kwemiphumela engalindelekile edinga ukuyekiswa kokwelashwa, okulandelayo kwabonwa:

• Ukwanda kwe-QC - 0,4%;
• Ukutheleleka kohlelo lwe-genitourinary - 0,3%;
• Ukuqhuma esikhunjeni - 0,2%;
• Ukuphazamiseka kwe-dyspeptic; 0,2%;
• Ukwephulwa kokuxhumana - 0,2%.

Imininingwane yezifundo yethulwa etafuleni.

Indlela Yokuhlola:

• Imvamisa kakhulu -> 0,1;
• Imvamisa -> 0.01, <0.1;
• Kaningi -> 0.001, <0.01.

Ukubuyekezwa kweDapagliflozin

Ngokwenhlolovo yabavakashi abathola izinsizakusebenza, abanesifo sikashukela abanemiphumela emibi, banelisekile ngemiphumela yokwelashwa. Abaningi bamiswa yizindleko zamaphilisi, kepha imizwa yomuntu siqu ehambisana nobudala, izifo ezenzeka ndawonye, ​​inhlala-kahle jikelele ngeke kube umhlahlandlela wokunqunywa kokuqokwa kukaForigi.

Inkambo yokwelashwa yomuntu siqu ingenziwa kuphela udokotela, uzothatha i-analogues ye-dapagliflozin (Jardins, Attokuan) uma inkimbinkimbi ingasebenzi ngokwanele.

Kwividiyo - izici zeDapagliflozin njengohlobo olusha lwemithi.