I-Vardenafil Dihydrochloride Ukwelapha I-Erectile Dysfunction 224785-91-5

Isenzo se-Pharmacological
Lesi sidakamizwa siyi-phosphodiesterase type 5 (PDE5) inhibitor. Ukuphathwa ngomlomo kwalesi sidakamizwa kungathuthukisa ngempumelelo ikhwalithi nobude besikhathi sokumiswa, futhi kuthuthukise izinga lempumelelo yokuphila kocansi ezigulini zesilisa ezine-erectile dysfunction. Ukuqaliswa nokugcinwa kwe-penile erection kuhlobene nokuxegiswa kwamaseli e-cavernosal abushelelezi emisipha, futhi i-cyclic guanosine monophosphate (cGMP) ingumxhumanisi wokuphumula kwamaseli e-cavernosal smooth muscle. Lesi sidakamizwa sivimbela ukubola kwe-cGMP ngokuvimbela uhlobo lwe-phosphodiesterase 5, ngaleyo ndlela kubangele ukuqoqwa kwe-cGMP, ukuphumula kwemisipha ebushelelezi ye-corpus cavernosum, nokumiswa kwepipi. Uma kuqhathaniswa ne-phosphodiesterase isozymes 1, 2, 3, 4, no-6, lesi sidakamizwa sinokukhethwa okuphezulu kohlobo 5 lwe-phosphodiesterase. Enye idatha ibonisa ukuthi ukukhetha kwayo kanye nomphumela ovimbelayo kuhlobo lwe-phosphodiesterase 5 kungcono kunezinye i-phosphodiesterase type 5 inhibitors. Uhlobo lwe-phosphodiesterase inhibitors lumbalwa.

Izakhiwo Zokwelapha kanye Nezicelo

1. Uma isetshenziswa kanye ne-CYP 3A4 inhibitors (njenge-ritonavir, i-indinavir, i-saquinavir, i-ketoconazole, i-itraconazole, i-erythromycin, njll.), ingavimbela i-metabolism yalesi sidakamizwa esibindini , yandisa ukuhlushwa kwe-plasma, yandise isigamu sempilo, futhi yandise ukusabela okubuhlungu, izinguquko ezibukwayo (ukushintsha kwe-fashion) ukukhukhumeza, i-priapism). Lo muthi kufanele ugwenywe uhlanganiswe ne-ritonavir kanye ne-indinavir. Lapho isetshenziswa ngokuhlanganiswa ne-erythromycin, ketoconazole, ne-itraconazole, umthamo omkhulu walesi sidakamizwa akufanele udlule u-5 mg, futhi umthamo we-ketoconazole ne-itraconazole akufanele udlule ku-200 mg.
2. Iziguli ezithatha ama-nitrate noma ezithola ukwelashwa kwe-nitric oxide donor kufanele zigweme ukusebenzisa lesi sidakamizwa ngokuhlangene. Indlela yayo yokusebenza iwukuqhubeka nokwandisaukuhlushwa kwe-cGMP, okuholela ekuthuthukisweni komphumela we-antihypertensive kanye nokwanda kwesilinganiso senhliziyo. Uma isetshenziswa kanye ne-α-receptor blockers, ingakhuphula umphumela we-antihypertensive futhi iholele ku-hypotension. Ngakho-ke, ukusetshenziswa kwalesi sidakamizwa akuvunyelwe kulabo abasebenzisa i-α-receptor blockers. Ukudla okunamafutha aphakathi (ama-30% ama-calories amafutha) akubanga nomphumela ophawulekayo ku-pharmacokinetics yomthamo owodwa womlomo we-20 mg yalesi sidakamizwa, futhi ukudla okunamafutha aphezulu (okungaphezu kwama-55% ama-calories amafutha) kungandisa isikhathi esiphezulu salesi sidakamizwa futhi kunciphise ukuhlushwa kwegazi kwalesi sidakamizwa Isilinganiso esiphezulu singaba ngu-18%.

I-Pharmacokinetics
Imuncwa ngokushesha ngemva kokuphathwa ngomlomo, i-bioavailability ephelele yethebhulethi yomlomo ingu-15%, kanti isikhathi esimaphakathi sokufika phezulu yi-1h (0.5-2h). Isixazululo somlomo 10mg noma 20mg, isikhathi esiphezulu esimaphakathi ngu-0.9h no-0.7h, isilinganiso esiphezulu sokuhlushwa kwe-plasma singu-9µg/L no-21µg/L, ngokulandelana, futhi ubude besikhathi somphumela wesidakamizwa singafinyelela ku-1h. Izinga lokubopha amaprotheni alo muthi cishe lingama-95%. I-1.5h ngemuva komthamo owodwa womlomo we-20 mg, okuqukethwe kwesidakamizwa esidodeni kungu-0.00018% womthamo. Umuthi ugaywa kakhulu esibindini nge-cytochrome P450 (CYP) 3A4, futhi inani elincane ligaywa yi-CYP 3A5 ne-CYP 2C9 isoenzymes. I-metabolite eyinhloko i-M1 eyenziwe yi-deethylation yesakhiwo se-piperazine yalesi sidakamizwa. I-M1 nayo inomphumela wokuvimbela i-phosphodiesterase 5 (cishe i-7% yokusebenza kahle okuphelele), futhi ukuhlushwa kwayo kwegazi cishe ku-26% yokuhlushwa kwegazi lomzali. , futhi ingaphinde isetshenziswe imetabolism. Amazinga okuphuma kwezidakamizwa ngendlela yama-metabolites endle nasemchamweni acishe abe ngu-91% kuya ku-95% no-2% kuye ku-6%, ngokulandelana. Isilinganiso sokugunyazwa sisonke singama-56 L ngehora, kanti uhhafu wezimpilo zekhompiyutha yomzali kanye ne-M1 zombili zingamahora ama-4 kuye kwayi-5.