Ertugliflozin API

Ultra-High Selective Inhibition of Renal SGLT2 Transporters

Lub Hom Phiaj Xaiv: Ertugliflozin nthuav tawm ntau dua 2,000-fold selectivity rau SGLT2 tshaj SGLT1 (feem ntau qhia hauv cov hnyuv me thiab myocardium), ua kom ntseeg tau meej inhibition ntawm lub raum qabzib reabsorption thaum tshem tawm cov kev tsis zoo ntawm lub plab zom mov.

Mechanism of Action: Competitively khi rau SGLT2 transporter nyob rau hauv S1 ntu ntawm lub raum proximal tubules, thaiv 30% -50% ntawm cov kua nplaum lim thiab nrog sodium reabsorption, txo cov ntshav qabzib thiab inducing natriuretic diuresis.

Restoration ntawm Tubuloglomerular tawm tswv yim & txo ntawm Intraglomerular Siab

Ntxiv sodium xa mus rau macula densa activates tubuloglomerular tawm tswv yim, ua rau afferent arteriolar constriction los txo intraglomerular hyperfiltration, hyperperfusion, thiab lub cev raug mob.

Metabolic Substrate Hloov & Kev Tiv Thaiv Mitochondrial

Induces ceev-zoo li metabolic xeev, txhawb lipolysis thiab hepatic ketogenesis (xws li, -hydroxybutyrate). Cardiomyocytes thiab lub raum hlwb siv ketone lub cev ua cov roj hluav taws xob muaj txiaj ntsig, nce ATP tsim thiab txo qis kev siv oxygen.

Cov lus nug tseem ceeb ntawm kev tshawb fawb yog li cas cov kab mob kis tau thiab tso zis tso zis tuaj yeem txav mus rau qhov sib txawv. Nyob rau hauv lub raum - txoj kev tshawb fawb txog kev puas siab puas ntsws tau piav qhia hauv Asmeskas cov khoom lag luam daim ntawv lo, ertugliflozin plasma raug nce ntxiv thaum lub raum ua haujlwm poob qis, thaum 24- teev tso zis tso zis ntau dua nrog raum tsis zoo. Cov tshuaj plasma ntau dua yog li ntawd tsis tas yuav qhia txog cov lus teb muaj zog ntawm cov piam thaj-excretion.

Cov kev tshawb fawb tsiaj thiab kev kho mob yuav tsum ntsuas lub raum ua haujlwm, cov ntshav qabzib lossis lim piam thaj, cov tshuaj plasma concentration, thiab tso zis tso zis ua ke. Kev txhais cov tshuaj pharmacodynamic los ntawm plasma concentration ib leeg tuaj yeem pom qhov sib txawv los ntawm tus qauv kab mob.

Ertugliflozin raug tshem tawm feem ntau los ntawm O-glucuronidation kho los ntawm UGT1A9 thiab UGT2B7, tsim ob lub glucuronide metabolites. CYP-kev sib haum xeeb oxidative metabolism yog ib txoj hauv kev me me. Ertugliflozin kuj yog ib qho substrate ntawm P-glycoprotein (P-gp) thiab BCRP. Cov khoom no ua rau nws muaj txiaj ntsig zoo rau kev tshawb fawb ntawm glucuronidation, metabolite txheeb xyuas, thiab kev thauj cov membrane.

Cov kev tshawb fawb sib cuam tshuam yuav tsum paub qhov txawv enzyme inhibition, enzyme induction, thiab transporter substrate raws li txoj cai. Ua tus thauj khoom substrate tsis, los ntawm nws tus kheej, tsim kom muaj kev cuam tshuam tseem ceeb hauv kev kho mob nrog txhua tus inhibitor ntawm tus thauj ntawd.

VERTIS CV tau soj ntsuam ertugliflozin hauv cov neeg mob ntshav qab zib hom 2 thiab tsim cov kab mob atherosclerotic cardiovascular. Nws cov txiaj ntsig tseem ceeb ntawm cov hlab plawv tau ua tiav raws li cov txheej txheem rau qhov tsis muaj qhov tsis zoo rau cov placebo; qhov tshwm sim yuav tsum tsis txhob piav raws li cov ntaub ntawv pov thawj ntawm superiority rau txo cov kab mob plawv loj. Cov tshuaj ntsuam xyuas tau tshaj tawm qhov kev pheej hmoo tsawg dua ntawm kev mus pw hauv tsev kho mob thawj zaug rau lub plawv tsis ua haujlwm, thaum tshawb xyuas lub raum tau muab lub hauv paus rau kev tshawb nrhiav ntxiv. Cov xwm txheej thiab kev txhais cov lej ntawm txhua qhov kawg yuav tsum tau hais cais.

Kev tshawb fawb txog kev nyab xeeb yuav tsum daws cov teeb meem cuam tshuam nrog SGLT2 inhibition. Tam sim no US daim ntawv lo ceeb toom txog ketoacidosis, ntim depletion, kab mob urinary, kab mob ntawm qhov chaw mos mycotic, necrotizing fasciitis ntawm lub perineum, thiab qis dua -limb amputation. Hypoglycemia kuj yuav tsum tau saib xyuas thaum siv ertugliflozin nrog insulin lossis insulin secretagogues. Ketoacidosis tuaj yeem tshwm sim yam tsis muaj qib ntawm hyperglycemia ib txwm xav tau, yog li kev nyeem cov ntshav qabzib ib leeg tsis tuaj yeem cais nws.

API thiab kev tshawb fawb tsiaj yuav tsum txheeb xyuas cov koob tshuaj rau kev ntsuas kev raug mob, lub raum ua haujlwm, cov kua dej, thiab ketone- cuam tshuam txog qhov kawg. Ib qho concentration uas zoo nkaus li muaj kev nyab xeeb hauv cov qauv ntawm tes tsis tuaj yeem hloov rov ua dua - koob tshuaj toxicology lossis kev ntsuas ntawm tib neeg kev pheej hmoo.

Hom 2 Ntshav Qab Zib & Qab Zib -Lipid Metabolic Disorders

Kev siv dav dav los ntsuas kev kho mob ntawm pancreatic - cell functions nyob rau hauv glucotoxicity, kev txhim kho ntawm insulin rhiab heev, thiab kev tswj ntawm hepatic gluconeogenesis.

Kev Tiv Thaiv Mob plawv & Kev Kho Mob Myocardial

Ua hauj lwm nyob rau hauv myocardial ischemia / reperfusion raug mob, plawv hypertrophy, thiab lub plawv tsis ua hauj lwm qauv los soj ntsuam nws cov kev ua tau zoo nyob rau hauv attenuating myocardial fibrosis, txhim kho endothelial muaj nuj nqi, thiab inhibiting vascular du leeg cell proliferation.

Diabetic Nephropathy & Raum Fibrosis (CKD)

Siv los ntsuas qhov txo qis ntawm cov zis albumin- rau- creatinine ratio (UACR), tsub kom lub raum tubular epithelial- mesenchymal hloov (EMT), thiab downregulation ntawm TGF- 1 / Smad signaling pathway.