Cov ntsiab lus dab tsi koj yuav tsum tau them sai sai rau thaum yuav Acetildenafil?

raw khoom Acetildenafil, tseem hu ua hongdenafil, yog Ameslikas tshuaj rau kev kho mob angina pectoris tsim thiab tsim los ntawm lub tuam txhab Pfizer hauv Tebchaws Meskas. Hauv kev sim tshuaj, nws tau pom tias nws cov nyhuv hauv kev kho mob ntawm angina pectoris yog qhov dav, tab sis nws muaj qhov tshwj xeeb hauv kev kho mob impotence. Qhov kev tshawb pom tsis txaus ntseeg no tau ua rau cov chaw tsim khoom tsuas yog tshaj tawm nrog cov tshuaj rau kev kho mob ntawm impotence. Lub US Food and Drug Administration (FDA) tau tso cai rau cov tshuaj raws li ib tug tshwj xeeb tshuaj rau kev kho mob ntawm impotence nyob rau lub Peb Hlis 27, 1997.

Dab tsi yog qhov xwm txheej ntawm hongdenafil hauv ntau lub tebchaws?

Acetildenafil (hongdenafil) yog cov tshuaj hluavtaws uas ua raws li phosphodiesterase inhibitor. Nws yog ib qho analog ntawm sildenafil (Viagra) uas tau kuaj pom nyob rau hauv ntau lub npe sib txawv ntawm cov khoom lag luam tshuaj aphrodisiac muag los txhawb libido thiab txo erectile kawg. Lub hauv paus ntsiab lus ntawm kev ualiab dinafilyog sib npaug rau sildenafil, thiab cov nyiaj ntxiv yog me ntsis tsawg dua sildenafil. Nws yog ib zaug hu ua sildenafil tsis tuaj yeem kuaj pom. Acetildenafil tau hloov kho los ntawm sildenafil citrate. Lub hauv paus ntsiab lus ntawm kev ua ntawm Acetildenafil liab yog sib npaug rau sildenafil citrate, thiab cov nyiaj ntxiv yog me ntsis tsawg dua sildenafil citrate. Cov qauv analogues ntawm xws li Daim Ntawv Tso Cai PDE 5 inhibitors (xws li sildenafil thiab vardenafil) yog tsim los kom tsis txhob muaj kev txwv kev cai lij choj ntawm kev muag tshuaj erectile kawg nyob rau sab hnub poob vim hais tias PDE 5 inhibitors feem ntau yog cov tshuaj noj thiab tiv thaiv los ntawm patents nyob rau sab hnub poob feem ntau. , Txawm li cas los xij, muaj kev zam rau kev tiv thaiv patent, uas tso cai rau lwm tus los tsim cov khoom tshiab raws li cov khoom qub. Raws li kev txhim kho ntxiv ntawm sildenafil thiab lwm yam khoom lag luam, hongdinafil tau ua kom zoo thiab ua tiav los ua pov thawj tias muaj PDE 5 inhibitory kev ua haujlwm hauv vitro. Nws kuj tseem muaj cov txiaj ntsig zoo ib yam hauv kev sim tsiaj, yog li nws tau dhau los ua cov khoom hloov pauv yav tom ntej. Txawm li cas los xij, thaum cov khoom tsis tau ua tiav cov txheej txheem kuaj thiab tsis tau xa cov txheej txheem patent daim ntawv thov, nws yog nrov thoob plaws lub ntiaj teb no, uas tsis tsuas yog cuam tshuam cov kev cai lij choj, tab sis kuj coj kev yooj yim rau qhov tsis meej ntawm cov khoom. Txawm li cas los xij, vim nws tsis paub cov txiaj ntsig, nws kuj ua rau muaj kev pheej hmoo loj rau kev noj qab haus huv, yog li tsis txhob siv yam tsis tau tso cai.

Dab tsi yog pharmacokinetics ntawm Acetildenafil?

Qhov nqus ntawmAcetildenafilyog sai tom qab kev tswj hwm qhov ncauj, thiab qhov tseeb bioavailability yog li 40 feem pua. Nws cov pharmacokinetic tsis yog proportional rau cov koob tshuaj nyob rau hauv qhov pom zoo koob tshuaj ntau. Nws tsuas yog tshem tawm cov metabolism hauv siab (cytochrome P450 isoenzyme 3A4 txoj hauv kev) thiab tsim cov metabolite nquag, uas nws cov khoom zoo ib yam li cov sildenafil. Thaum muaj zog inhibitors ntawm cytochrome P450 isoenzyme 3A4 (CYP450 3A4) xws li erythromycin, ketoconazole, thiab itraconazole thiab nonspecific inhibitors ntawm cytochrome P450 (CYP450) xws li cimetidine thiab sildenafil tau siv ua ke, nws yuav ua tau ib nrab ntawm {elimination 1} Lub neej ntawm Acetildenafil thiab nws cov metabolites yog li 4 teev. Thaum muab 25 100 mg rau ntawm lub plab khoob, qhov siab tshaj plaws plasma concentration (Cmax) mus txog 127 560 ng / ml hauv li 1 teev. Kev xaiv ntawm Acetildenafil los yog nws cov metabolite tseem ceeb N- desmethyl rau PDE5 yog li 50 feem pua, thiab cov protein khi tus nqi yog 96 feem pua. Ntawm qhov siab tshaj plaws plasma concentration ntawm tag nrho rhododenafil, Cmax ntawm dawb rhododenafil yog 22ng / ml. Tom qab kev tswj hwm qhov ncauj lossis cov hlab ntsha, Hongdinafei feem ntau yog tawm los ntawm cov quav hauv daim ntawv ntawm cov tshuaj metabolites (kwv yees li 80 feem pua ​​​​ntawm cov koob tshuaj hauv qhov ncauj), thiab ib qho me me tau tawm ntawm cov zis (kwv yees li 13 feem pua ​​​​ntawm qhov ncauj koob tshuaj).

Pharmacokinetics ntawm cov neeg tshwj xeeb: cov neeg laus: qhov kev tshem tawm ntawm sildenafil hauv cov neeg laus noj qab haus huv tuaj yeem pab dawb (Ntau dua lossis sib npaug rau 65 xyoos) txo qis, thiab cov ntshav dawb concentration yog li 40 feem pua ​​​​siab dua li cov tub ntxhais hluas noj qab haus huv tuaj yeem pab dawb (18-45 xyoo. qub). Sildenafil citrate fwj lub raum tsis txaus: cov neeg tuaj yeem pab dawb (creatinine tshem tawm sib npaug li 50-80ml / min) thiab nruab nrab (creatinine clearance sib npaug li 30-49ml / min) raum puas tsis muaj kev hloov pauv hauv cov tshuaj pharmacokinetics ntawm ib koob tshuaj ntawm qhov ncauj ntawm sildenafil 50mg. Hauv cov neeg ua haujlwm pab dawb uas muaj lub raum puas tsuaj loj (creatinine tshem tawm Tsawg dua lossis sib npaug li 30ml / min), qhov kev tshem tawm ntawm sildenafil txo qis, thiab thaj chaw hauv qab lub sijhawm siv tshuaj (AUC) thiab Cmax yuav luag ob npaug piv nrog cov neeg tuaj yeem pab dawb hauv tib pab pawg hnub nyoog yam tsis muaj lub raum. kev puas tsuaj.

Lub siab ua haujlwm tsis zoo: Sildenafil tshem tawm txo qis hauv cov neeg tuaj yeem pab dawb uas muaj cirrhosis (Child-Pugh qib A thiab b), thiab AUC thiab Cmax tau nce 84 feem pua ​​​​thiab 47 feem pua ​​​​raws li piv nrog cov neeg ua haujlwm pab dawb uas tsis muaj daim siab puas hauv tib lub hnub nyoog. Yog li ntawd, muaj hnub nyoog tshaj 65 xyoos, daim siab ua haujlwm puas tsuaj thiab lub raum ua haujlwm hnyav yuav ua rau kom nce qib plasma sildenafil. Qhov pib koob tshuaj ntawm tus neeg mob no yuav tsum yog 25mg

Kev sib piv ntawm pharmacokinetics ntawmhongdenafilthiab lwm yam khoom zoo sib xws

Ib nrab inhibition tus nqi (IC50), titer siv, thiab selectivity ntawm phosphodiesterase. Qhov ib nrab inhibition tus nqi ntawm hongdenafil rau phosphodiesterase-5 yog 7.6 nanomoles (nm). Piv nrog rau sildenafil, nws cov txheeb ze titer siv yog (1: 1). Nyob rau tib lub sijhawm, phosphodiesterase-6 tuaj yeem cuam tshuam los ntawm hongdinafei. Rau qhov yooj yim ntawm kev sib piv, qhov tsis sib xws ntawm hongdenafil thiab lwm yam sildenafil analogs tau qhia hauv cov lus hauv qab no. Ntawm lawv, sildenafil yog niam txiv tus nqi ntawm cov nqi txheeb ze. Thaum tus txheeb ze titer siv tsawg dua ib qho, cov tshuaj muaj zog tshaj nws niam cov tshuaj. Nws yuav tsum raug sau tseg tias thaum muaj ntau yam txiaj ntsig hauv ib lub xov tooj ntawm tes, nws qhia tau hais tias cov ntaub ntawv muab los ntawm cov ntaub ntawv sib txawv ntawm cov ntaub ntawv sib txawv ntawm ib leeg, thiab cov khoom sib txuas hauv cov lus tau ntsuas hauv daim ntawv ntawm cov tshuaj ntxiv. Nyob rau hauv lub rooj, muaj ob peb yam ntaub ntawv ntawm sildenafil, vardenafil, thiab tadalafil, thiab cov ntaub ntawv uas twb muaj lawm yog ntsuas los ntawm lub in vitro inhibition xeem ntawm phosphodiesterase-5 thiab phosphodiesterase-6. Txij li thaum kev nyab xeeb thiab kev ua tau zoo ntawm sildenafil analogs tsis tau saib xyuas thiab tshuaj xyuas, nws cov tshuaj preclinical pharmacological tsis meej thiab toxicity tsis meej. Nws tuaj yeem pom los ntawm cov lus hais tias qhov sib txheeb titer siv ntawm qee cov analogs yog ntau dua li ntawm sildenafil.

Toxicity to date, sildenafil's analogs are non{{0}}toxic, but some risks that may lead to toxicity have been documented. For example, it is possible that the dose of sildenafil reaches 60 mg per capsule. In the inhibition test of phosphodiesterase-6 in vitro (concentration range: 0.030 to 30 Nanomole) by Ballard et al., hongdenafil inhibited phosphodiesterase-6 in bovine retina, and this antagonistic mechanism has been pointed out in many kinds of literature to be positively correlated with visual impairment.

Cov kev mob tshwm sim tam sim no, tsis muaj cov ntaub ntawv kho mob tshwm sim ntawm sildenafil analogs. Txawm li cas los xij, piecemeal kho mob tuaj yeem muab qee cov lus qhia rau nws cov kev mob tshwm sim. Piv txwv li, nyob rau hauv ntau yam kev kawm ntawv cov ntaub ntawv, cov neeg mob feem ntau muaj kev phiv thaum noj tshuaj aphrodisiac uas muaj sildenafil analogs. Hauv Hong Kong, tus txiv neej hnub nyoog 28 xyoo tau tsim cov tsos mob ataxia xws li kev tsis muaj zog tom qab noj tshuaj ntxiv uas muaj hongdenafil rau yim hnub sib law liag.