LGD-4033 Kuayog cov kua ntawm cov kua mis ntawm lingandrol (LGD-4033), feem ntau yaj nyob rau hauv cov kuab tshuaj xws li Peg-400, ethanol, lossis glycerin kom txhim kho kev nqus cov nqi. Ua ib qho kev xaiv Androgen Revenor Modulator (sarm), nws tsuas yog cov nqaij mos thiab cov leeg nqaij tawv, thaum txo cov kev cuam tshuam ntawm anabolic (xws li hepatotoxicity lossis androgenic cuam tshuam).
Nws tau txais txiaj ntsig zoo ntawm kev siv tau ntawm txoj kev hloov kho tau yooj yim, uas feem ntau yog ntsuas siv cov roj ntsha lossis cov twj tso kua mis. Qhov kev pom zoo sib xws yog 5 - 10 mg / ml. Cov neeg siv feem ntau yuav siv 5-20 mg txhua hnub tsis pub dhau ib lub sijhawm 8-12, thiab tuaj yeem saib xyuas kev txhim kho hauv cov leeg, lub zog, thiab rov muaj peev xwm. Txawm li cas los xij, nws tuaj yeem ua rau mob me me testosterone, qaug zog, lossis mob taub hau, thiab lub sijhawm kev nyab xeeb ntev tsis tau pom meej.
Vim tias tsis tau pom zoo los ntawm FDA, cov khoom no tsuas yog muag raws li kev tshawb fawb tshuaj thiab raug txwv tsis pub siv los ntawm cov koom haum ncaws pob (xws li Wada). Thaum kev yuav khoom, saib xyuas yuav tsum tau them rau kev coj dawb huv thiab kev nyab xeeb kom tsis txhob muaj kev pheej hmoo lossis paug.
|
|
|
Ligandrol (LGD-4033) HMOOV COA
Kev Tshawb Xyuas Kev Ruaj Ntseg
Tshuaj Muaj Peev Xwm
LGD-4033 KuaYog qhov tsis -} steroidal xaiv xaiv Androgen tus receptor modulator (sarm), nrog cov tshuaj ruaj khov. Txawm li cas los xij, cov xwm txheej hauv qab no yuav tsum tau sau tseg:
Cia ib puag ncig:Nws yuav tsum tau muab khaws cia ntawm -20℃nyob rau hauv ib tug tub yees txias thiab muab tso rau hauv ib qho chaw nyob hauv inert kom tiv thaiv noo noo (Hygroscopicity).
Solubility:Nws yog me ntsis soluble hauv chloroform (raws li kev mob cua sov), methanol, thiab muaj solubility tsis tshua muaj. Cov qauv ua kua yuav raug txhim kho nyob rau hauv solubility thiab kev ruaj khov los ntawm kev kho cov kuab tshuaj (xws li ethanol), tab sis cov kuab tshuaj uas muaj kev sib txuas yuav tsum zam.
Lub teeb kis thiab oxidation:Ntev -} Tod raug rau lub teeb lossis oxygen yuav ua rau kev ua phem. Nws raug nquahu kom siv lub teeb - ntawv pov thawj fwj thiab muaj kev tiv thaiv nrog cov pa roj nitrogen.
Npaj Kev Nyab Xeeb Sib Tw
Kev pheej hmoo ntawm cov kua dosage daim ntawv:Piv nrog cov hmoov zoo, ua kua Dosage Sai yog ntau dua feem ntau tau rau hydrolysis, oxidation lossis microbial paug. Nws yog qhov tsim nyog los txuas lub txee txee los ntawm kev ntxiv cov stabilizers (xws li cov tshuaj tiv thaiv kab mob (PKA ntawm LGD-4033 yog 12.06, thiab qhov chaw tsis muaj zog alkaline yuav ruaj khov).
Ib nrab ntawm lub neej ua haujlwm:Kev tshem tawm ib nrab - lub neej ntawm LGD-4033 yog 2433 yog 2433 yog 2433 yog 2433 yog 2433 yog 2433 yog 24-36 teev, tab sis qhov kev ruaj khov ntawm daim foos ua kua xav tau. Nyob rau tam sim no, tsis muaj cov ntaub ntawv pej xeem qhia tias cov kev ua kua tshuaj yuav ua rau muaj kev ua kom luv luv, tab sis xws li 40℃/ 75% rh mob).
Tus neeg siv tswv yim thiab ntsuas cov ntaub ntawv
Qee tus neeg siv tau tshaj tawm tias raws li kev cia khoom kom raug (lub teeb {{}} Cov ntaub ntawv ua haujlwm, thiab nyob rau ntawm qhov chaw ua kua), tab sis cov kev soj ntsuam cov tshuaj xyuas tau ntev li cas.
Cov khoom lag luam ywj pheej pom tias qee cov lag luam muaj cov kev ua lag luam muaj kev cuam tshuam (± 15%) lossis tshaj qhov kev txwv tsis zoo, uas yuav cuam tshuam kev nyab xeeb thiab kev nyab xeeb.
Kev Ntsuas Kev Nyab Xeeb
Cov chaw soj ntsuam cov ntaub ntawv
Theem Kuv Tau Kev Sim:Kev Noj Qab Haus Huv Cov Txiv Neej Coj 1 {- 3} {{{{} {ceeb (HDL-C) tsawg zuj zus).
Ntu II Kev Sim:Hauv kev sim rau cov neeg mob uas muaj pob txha pob ntseg, qee cov kev kawm paub me me ntawm transaminases, tab sis tsis ncav cuag tus qauv ntawm daim siab toxicity.
Ntev - Term Txaus ntshai:Tam sim no tsis muaj cov ntaub ntawv tshaj li 12 lub lim tiam ntawm kev siv tshuaj tsis tu ncua, thiab cov kev pheej hmoo ntawm cov tshuaj tiv thaiv Axis, thiab tsis paub cov ntaub so ntswg sib txuam.
Cov kev pheej hmoo tshwj xeeb ntawm cov kua tsim
Ntse muab qhov tseeb:Cov qauv ua kua yuav tsum muaj cov kev ntsuas ntsuas ntsuas siv cov quav lossis khob mis nyuj, thiab ua haujlwm tsis zoo yuav ua rau muaj kev pheej hmoo noj (± 10%), nce kev pheej hmoo ntawm cov kev pheej hmoo.
Hnyav Kev Nyab Xeeb:Qee cov khoom ua kua tau siv propylene glycol lossis ethanol li kuab tshuaj, thiab ntev}} sij hawm}} lub sij hawm tsis xis nyob lossis lub siab ris nra.
Microbial kev sib kis:Tsis -} susile cov hmoov av yuav ua rau cov kab mob tsis huv, thiab kev nyab xeeb yuav tsum ua kom muaj kev ua kom tsis muaj menyuam yaus.
Tus neeg siv lub tswv yim tiag tiag
Cov kev phiv:Mob taub hau (15%), lub qhov ncauj qhuav (10%), cov leeg nqaij (8%), thiab cov uas tsis tshua muaj siab thiab thim rov qab.
Cov kev sib raug zoo:A few users reported jaundice (a sign of liver damage) or hypertension, which may be related to excessive dosage (>10 mg / hnub) lossis ib tus neeg ua haujlwm tau.
Kev cia siab thiab rho tawm cov tshuaj tiv thaiv:Mam li nco dheev siv tom qab ntev - tsis siv yuav ua rau tsis muaj zog lossis tsis muaj pov thawj ntawm kev quav.
Kev ntsuam xyuas thiab kev pom zoo
Lub ntsiab lus ruaj khov
Cov kua tsim los ntawm LGD -}}}}}}}}}}}}}}}}}}}}}}}}}}}} tuaj yeem nyob ruaj khov nyob rau hauv qis qis, lub teeb pov thawj, thiab ntim khoom. Txawm li cas los xij, nws raug nquahu kom xaiv cov khoom uas tau sim los ntawm ib tus neeg thib peb los xyuas kom meej thiab huv. Tom qab qhib, cov kua yuav tsum tau muab faib thiab khov kom tsis txhob ua kom khov thiab yaj.
Kev Nyab Xeeb Kev Ruaj Ntseg
Kev Siv Luv luv (4-8 lub lis piam): Siv cov tshuaj tsawg (tsawg dua los yog sib npaug, tab sis ntshav lipid yuav tsum tau saib xyuas.
Kev siv ntev ntev: qhov kev pheej hmoo tsis paub, thiab nws tsis pom zoo rau qhov tsis - kev kho mob.
Cov poj niam cev xeeb tub: cov poj niam cev xeeb tub, cov menyuam yaus, cov neeg mob muaj prostate lossis mob qog nqaij hlav cancer, thiab cov neeg mob nrog cov kab mob plawv.
Kev Siv Cov Lus Cog Tseg
Kev tswj koob: rau thawj -} cov neeg siv lub sijhawm, pib txij 2 mg / hnub thiab maj mam hloov mus rau lub hom phiaj koob.
Kev tswj kev ncig mus los: Siv txuas ntxiv tsis pub dhau 8 lub lis piam, tom qab ntawd yauv mus 4 lub lis piam ntawm PCT (xws li tamoxife hormones.
Kev soj ntsuam cov ntsuas: Kev kuaj mob tsis tu ncua, HDL {}} C, alt / eth / ant), thiab ntshav siab thaum lub sij hawm noj tshuaj.
Ua raws cai: LGD -}}}} 4033 yog teev raws li kev txwv tsis pub los ntawm lub ntiaj teb anti-doping koom haum (Wada). Cov neeg ncaws pob yuav tsum zam kev siv nws.
Kev nqus thiab bioavailability
Kev nqus tau lub tshuab thiab qhov ncauj zoo
LGD-4033 Kua, raws li tsis {{0} steroidal xaiv xaiv Androgen tus neeg txais nyiaj (slar), muaj cov tseem ceeb hauv nws lub qhov ncauj zoo nkauj (kwv yees li 90%). Cov yam ntxwv no los ntawm cov qauv molecular ntawm LGD - alkylation txheej txheem ntawm cov khoom lag luam metabolic los ntawm thawj lub siab nyhuv hauv daim siab.
Molecular Cov yam ntxwv:Lipophilicity (logp ≈ 3.5) thiab qhov hnyav molecular hnyav (338.25 g / mol) ntawm lub plab zom mov ntawm mucosa ntawm pass diffusion. Cov qauv ua kua tej zaum yuav tau txhim kho ntxiv rau hauv solubility los ntawm kev ua kom zoo dua ntawm glycol lossis ethanol), tab sis saib xyuas yuav tsum tau them rau lub peev xwm ua kom muaj kev cuam tshuam ntawm lub plab zom mov ntawm cov kuab tshuaj.
Kev nqus tus nqi:Cov kev tshawb fawb preclinical tau qhia tias LGD-4033 ncav cuag cov ntshav ntshav siab tshaj plaws (CMAX) 2-4 teev tom qab kev tswj hwm qhov ncauj. Cov qauv ua kua yuav ua rau lub sijhawm ua kom ntev rau 1-2 teev vim tsis muaj kev ua kom tiav cov txheej txheem ua kom tau raws li tib neeg kev sim siab.
Khoom noj khoom haus cawv:Lub siab - Cov khoom noj rog rog rog yuav ncua sij hawm nqus (Tmax ntev los ntawm 1-2 teev), tab sis nws tsis cuam tshuam rau tag nrho cov raug (AUC). Yog li ntawd, nws pom zoo kom noj cov tshuaj rau ntawm lub plab khoob kom txo tau cov kev sib txawv.
Yam cuam tshuam rau bioavailability
Cov kuab tshuaj thiab tsim txheej txheem
Kev xaiv cov kuab: Cov qauv ua kua feem ntau siv polyethylene glycol 400 (Peg400 (ethanol, lossis dimethyl sulfoxide (DMOPS) raws li cov kuab tshuaj. Peg400 tuaj yeem ua rau solubility thiab muaj kev nyab xeeb ntau dua, tab sis nws tuaj yeem txo cov tshuaj preatability; Ethanol tuaj yeem txhim kho Membrane permeability, tab sis ntev - kev siv lub zog yuav txhawb lub plab zom mov.
Kev nyuaj nyuaj: LGD-4033 xav kom tsis txhob muaj hydrolysis (tshwj xeeb tshaj yog nyob rau hauv cov aqueous cov kuab tshuaj) thiab oxidation dectradation hauv cov kua tsim. Ntxiv cov tshuaj tua kab mob tshuaj tua kab mob (xws li vitamin e) thiab khaws cia rau hauv qhov chaw tsaus tuaj yeem txuas lub txee ntev txog 12-18 lub hlis.
Tus neeg sib txawv thiab cov metabolism
CYP3A4 polymorphism: LGD-4033 feem ntau yog metabolized los ntawm daim siab enzyme cyp3A4, tsim kom muaj cov metabolite qub. CYP3A4 Gene Polymorphism tuaj yeem ua rau sib txawv hauv Metabolic tus nqi, thiab koob tshuaj opapeator los ntawm kho cov tshuaj xyuas (TDM) yog qhov tsim nyog.
Ua ntej -} Cov nyhuv Pass: Txawm hais tias qhov ncauj pib yog siab li 90%, muaj peev xwm ib tug neeg muaj peev xwm tseem ua rau muaj kev hloov pauv ntshav hauv ntshav (± 20%).
Kev sib cuam tshuam yeeb tshuaj
CYP3A4 inibitors: thaum ua ke nrog cyps muaj zog muaj xws li Ketoconazole thiab ritonavir thiab ritonavir thiab ritonavir, cov kev pheej hmoo ntawm cov kev pheej hmoo ntawm cov kev mob tshwm sim.
CYP3A4 INCERUCERS: Thaum ua ke nrog Cyp3A4 tus yuam sij xws li Rifampicin thiab Carmustine accelerates, muaj peev xwm ua rau ib qho kev txo qis hauv kev ua tau tshuaj.
Cov ntaub ntawv hauv tsev kho mob thiab koob tshuaj optimization
Dose -} Kev Txhim Kho
Linear pharmacokinetics:Hauv 1-10 MG / Diub koob ntau npaum li cas, cov tshuaj ntshav ntau yog sib xws rau cov koob tshuaj. Cov qauv ua kua tau xav tau los xyuas kom meej cov koob tshuaj raug los ntawm kev ntsuas ntsuas (xws li ntsuas dej lossis ntsuas khob) kom tsis txhob ua yuam kev (± 10%).
Cov tshuaj tau txais:
Cov leeg - Lub sijhawm ua lub sijhawm: 4 {{}} txhua hnub, rau kev noj haus muaj protein ntau thiab kev kawm tawm tsam.
Lub sijhawm rog poob: 2-5 mg ib hnub txhua hnub, tiv thaiv cov nqaij ntshiv mob thiab tsis txhob mob leeg.
Cov Neeg Laus: 1 {{{{}}} 2 mg txhua hnub, nrog saib xyuas cov pob txha ceev thiab prostate-tshwj xeeb antigen (PSA).
Ib nrab - lub neej thiab koob sib caij
Tshem tawm ib nrab - lub neej:24 {- 36 teev, txhawb nqa ib zaug cov thawj coj txhua hnub. Cov kua tsim ua kom paub tseeb tias kev sib faib ntawm cov metabolites tsis tshaj qhov txwv thaum lub sijhawm cia (xws li -20℃kom khov).
Kev tswj kev ncig xyuas:Ntev -}}}}}}}}}}}}}} Kev Siv Testosterous (li 50% txo), thiab nws raug pom zoo los ntawm 4 lub lis piam ntawm pct (xws li tamoxifen 20 mg / hnub).
Kev Nyab Xeeb Kev Nyab Xeeb thiab Kev Nyab Xeeb
Sab Ua Haujlwm Kev Ntsuam Xyuas
Luv -} Lub sijhawm tshwm sim: mob taub hau (10%), thiab hloov music (5%), feem ntau ntawm cov uas muaj me me thiab thim rov qab.
Ntev - Term Txaus ntshai:
Lipid metabolism tsis sib xws: HDL {{}} c c txo los ntawm 40%, ldl {}} C nce los ntawm 30%, muaj kev pheej hmoo ntshav siab. Hepatotoxicity: Hauv qee kis, ceeb toom qhia txog kev nce qib hauv cov qib transaminase (alt / ast> 3 zaug kev soj ntsuam ntawm daim siab ua haujlwm yog qhov yuav tsum tau ua.
Hormone Kev Txiaj Ntsig: Tag nrho cov testosterone txo qis dua li 50%, thiab testosterone dawb txo qis dua 40%. Nws yog ib qho tsim nyog los rov qab los ntawm PCT.
Kev ceev faj thiab cov contraindications
Contraindicated ntau: Cov poj niam cev xeeb tub, cov menyuam yaus, cov neeg mob uas muaj mob prostate lossis mob cancer mis yuav tsum tsis txhob siv.
Kev sib xyaw ua ke: Zam kev siv ua ke nrog cov tshuaj tiv thaiv (xws li carbamazepine) lossis tshuaj tiv thaiv kab mob (xws li ritonavir (xws li ritonavir) los tiv thaiv kev sib txuas lus metabolic.
Cov kev pheej hmoo tshwj xeeb ntawm cov kua ua kua: yuav ceev faj rau cov hnoos qeev (tsis yog {{{{}} xyoo toxicity (xws li ethanol).
Cim npe nrov: LGD-4033 Kua, tus neeg muag khoom, chaw tsim khoom, Hoobkas, lag luam wholesale, yuav, nqe, loj, loj, rau muag