natgillin/translations-raw huggingface dataset:
Primary endpoint in the sub-group of patients with renal impairment The APEX Study evaluated efficacy in 40 patients with renal impairment (i. e., baseline serum creatinine > 1.5 mg/ dl and < =2.0 mg/ dl).
Primarni opazovani dogodek v podskupini bolnikov z okvaro delovanja ledvic V študiji APEX je bila ocenjena učinkovitost pri 40 bolnikih z okvaro delovanja ledvic (tj. izhodiščna vrednost kreatinina v serumu > 1, 5 mg/ dl in ≤ 2, 0 mg/ dl).
For renally impaired subjects who were randomized to allopurinol, the dose was capped at 100mg QD.
Pri bolnikih z okvaro ledvic, ki so bili naključno razporejeni v skupino, ki je prejemala alopurinol, je bila višina odmerka omejena na 100 mg enkrat na dan.
ADENURIC achieved the primary efficacy endpoint in 44% (80 mgQD), 45% (120 mg QD), and 60% (240 mg QD) of patients compared to 0% in the allopurinol 100 mg QD and placebo groups.
Primarni opazovani dogodek učinkovitosti je bil v skupini, ki je jemala zdravilo ADENURIC, dosežen pri 44% (80 mg enkrat na dan), 45% (120 mg enkrat na dan) in 60% (240 mg enkrat na dan) bolnikov v primerjavi z 0% v skupinah, ki so prejemale alopurinol 100 mg enkrat na dan ali placebo.
There were no clinically significant differences in the percent decrease in serum uric acid concentration in healthy subjects irrespective of their renal function (58% in the normal renal function group and 55% in the severe renal dysfunction group).
Klinično pomembnih razlik v odstotku znižanja koncentracije sečne kisline v serumu pri zdravih prostovoljcih niso opazili ne glede na njihovo ledvično delovanje (58% v skupini z normalnim delovanjem ledvic in 55% v skupini z hudo motnjo delovanja ledvic).
Primary endpoint in the sub group of patients with sUA ≥ 10 mg/ dl Approximately 40% of patients (combined APEX and FACT) had a baseline sUA of ≥ 10 mg/ dl.
Primarni opazovani dogodek v podskupini bolnikov z vrednostmi sečne kisline v serumu ≥ 10 mg/ dl Približno 40% bolnikov (iz obeh študij APEX in FACT) je imelo izhodiščno vrednost sečne kisline v serumu ≥ 10 mg/ dl.
In this subgroup ADENURIC achieved the primary efficacy endpoint in 41% (80 mg QD), 48% (120 mg QD), and 66% (240 mg QD) of patients compared to 9% in the allopurinol 300 mg/ 100 mg QD and 0% in the placebo groups.
V tej podskupini je bil primarni opazovani dogodek učinkovitosti dosežen pri 41% (80 mg enkrat na dan), 48% (120 mg enkrat na dan) in 66% (240 mg enkrat na dan) bolnikov v skupinah, ki je jemala zdravilo ADENURIC v primerjavi z 9% v skupini, zdravljeni z alopurinolom 300 mg ali 100 mg enkrat na dan, in 0% v placebo skupini.
Clinical Outcomes: proportion of patients requiring treatment for a gout flare and tophi size change The proportion of subjects requiring treatment for a gout flare (APEX and FACT Study) was numerically lower in the groups that achieved an average post-baseline serum urate level < 6.0 mg/ dl, < 5.0 mg/ dl, or < 4.0 mg/ dl compared to the group that achieved an average post- baseline serum urate level ≥ 6.0 mg/ dl during the last 32 weeks of the treatment period (Week 20-Week 24 to Week 48 - 52 intervals).
Delež bolnikov, pri katerih je bilo treba zdraviti izbruh protina in pri katerih se je spremenila velikost tofov Delež bolnikov, pri katerih je bilo treba zdraviti izbruh protina (v študijah APEX in FACT), je bil številčno nižji v skupinah, ki so dosegle povprečno vrednost urata v serumu po izhodišču < 6, 0 mg/ dl, < 5, 0 mg/ dl ali < 4, 0 mg/ dl, v primerjavi s skupino, ki je dosegla povprečne vrednosti urata v serumu po izhodišču ≥ 6, 0 mg/ dl v obdobju zadnjih 32 tednov zdravljenja (v intervalih teden 20- 24 do teden 48- 52).
10 Two years of data from the Phase 3 Open Label Extension study showed that the maintenance of serum urate levels < 6 mg/ dl (< 357 µmol/ l) resulted in a decrease in the incidence of gout flares with less than 3% of subjects requiring treatment for a flare (i. e. more than 97% of patients did not require treatment for a flare) at Month 16-24.
9 Dveletni podatki odprte podaljšane študije 3. faze so pokazali, da je povzročilo vzdrževanje vrednosti urata v serumu < 6 mg/ dl (< 357 µmol/ l) zmanjšanje pojavnosti izbruhov protina tako, da je bilo treba zaradi izbruha v 16- 24. mesecu zdraviti manj kot 3% bolnikov (tj. več kot 97% bolnikov zaradi izbruha ni bilo treba zdraviti).
This was associated with a reduction of tophus size leading to complete resolution in 54% of subjects at Month 24.
To je bilo povezano z zmanjšanjem velikosti tofov, ki so pri 54% bolnikih v 24. mesecu popolnoma izginili.
During the phase 3 clinical studies, mild liver function test abnormalities were observed in patients treated with febuxostat (3.5%).
V kliničnih študijah 3. faze so opazili blage nenormalnosti rezultatov pri testih delovanja jeter pri bolnikih, zdravljenih s febuksostatom (3, 5%).
These rates were similar to the rates reported on allopurinol (3.6%) (see section 4.4).
O podobnem deležu so poročali tudi za alopurinol (3, 6%) (glejte poglavje 4. 4).
Increased TSH values (> 5.5 µIU/ ml) were observed in patients on long-term treatment with febuxostat (5.0%) and patients with allopurinol (5.8%) in the long term open label extension studies (see section 4.4).
V dolgoročnih odprtih podaljšanih študijah so povišane vrednosti TSH (> 5, 5 µi. e. / ml) opazili pri bolnikih, ki so se dolgoročno zdravili s febuksostatom (5, 0%), in pri bolnikih, ki so se zdravili z alopurinolom (5, 8%) (glejte poglavje 4. 4).
The total exposure to ADENURIC in phase 3 pivotal studies and long-term extension studies is greater than 2700 patient-years.
Skupna izpostavljenost zdravilu ADENURIC v ključnih študijah 3. faze in dolgoročnih podaljških študij je večja kot 2. 700 bolniških let (“ patient- years ”).
In healthy subjects, maximum plasma concentrations (Cmax) and area under the plasma concentration time curve (AUC) of febuxostat increased in a dose proportional manner following single and multiple doses of 10 mg to 120 mg.
Pri zdravih prostovoljcih so se največje plazemske koncentracije (Cmax) in površine pod krivuljo plazemskih koncentracij v odvisnosti od časa (AUC) febuksostata po enkratnem in pri ponavljajočih se odmerkih 10 mg do 120 mg poviševale sorazmerno z odmerkom.
For doses between 120 mg and 300 mg, a greater than dose proportional increase in AUC is observed for febuxostat.
Za odmerke med 120 mg in 300 mg so za febuksostat opazili povišanje AUC, ki je bilo večje od sorazmernega z odmerkom.
Febuxostat has an apparent mean terminal elimination half-life (t1/ 2) of approximately 5 to 8 hours.
Povprečna navidezna končna razpolovna doba izločitve (t1/ 2) febuksostata je približno 5 do 8 ur.
Population pharmacokinetic/ pharmacodynamic analyses were conducted in 211 patients with hyperuricemia and gout, treated with ADENURIC 40-240 mg QD.
Analize populacijske farmakokinetike/ farmakodinamike so bile izvedene pri 211 bolnikih s hiperurikemijo in protinom, zdravljenih z zdravilom ADENURIC 40- 240 mg enkrat na dan.
In general, febuxostat pharmacokinetic parameters estimated by these analyses are consistent with those obtained from healthy subjects, indicating that healthy subjects are representative for pharmacokinetic/ pharmacodynamic assessment in the patient population with gout.
Na splošno se parametri farmakokinetike febuksostata, ocenjeni v teh analizah, ujemajo s tistimi, ki so jih pridobili pri zdravih osebah, kar kaže, da so zdrave osebe dovolj za oceno farmakokinetike/ farmakodinamike pri bolnikih s protinom.
Absorption Febuxostat is rapidly (tmax of 1.0-1.5 h) and well absorbed (at least 84%).
Absorpcija Febuksostat se hitro (tmax 1, 0- 1, 5 h) in dobro absorbira (vsaj 84%).
After single or multiple oral 80 and 120 mg once daily doses, Cmax is approximately 2.8-3.2 µg/ ml, and 5.0- 5.3 µg/ ml, respectively.
Po enkratnem ali ponavljajočem se peroralnem odmerku 80 mg enkrat na dan je Cmax približno 2, 8- 3, 2 µg/ ml, pri odmerku 120 mg pa 5, 0 - 5, 3 µg/ ml.
Following multiple oral 80 mg once daily doses or a single 120 mg dose with a high fat meal, there was a 49% and 38% decrease in Cmax and a 18% and 16% decrease in AUC, respectively.
38%, AUC pa za 18% oz.
Distribution The apparent steady state volume of distribution (Vss/ F) of febuxostat ranges from 29 to 75 l after oral doses of 10-300 mg.
Porazdelitev Navidezni volumen porazdelitve v stanju dinamičnega ravnovesja (Vss/ F) febuksostata je po peroralnih odmerkih 10- 300 mg od 29 do 75 l.
The plasma protein binding of febuxostat is approximately 99.2%, (primarily to albumin), and is constant over the concentration range achieved with 80 and 120 mg doses.
Delež vezave febuksostata na plazemske beljakovine je približno 99, 2%, (primarno na albumin) in je enak pri koncentracijah, doseženih z odmerki 80 mg in 120 mg.
Plasma protein binding of the active metabolites ranges from about 82% to 91%.
Delež vezave aktivnih presnovkov na plazemske beljakovine je približno 82% do 91%.
11 Metabolism Febuxostat is extensively metabolized by conjugation via uridine diphosphate glucuronosyltransferase (UDPGT) enzyme system and oxidation via the cytochrome P450 (CYP) system.
Presnova Večji del presnove febuksostata poteka s konjugacijo prek encimskega sistema uridil difosfat glukuroniltransferaze (UDPGT) in z oksidacijo s citokromi P450 (CYP).
Four pharmacologically active hydroxyl metabolites have been identified, of which three occur in plasma of humans.
Identificirali so štiri farmakološko aktivne hidroksi presnovke, od katerih se trije pojavljajo v plazmi pri ljudeh.
In vitro studies with human liver microsomes showed that those oxidative metabolites were formed primarily by CYP1A1, CYP1A2, CYP2C8 or CYP2C9 and febuxostat glucuronide was formed mainly by UGT 1A1, 1A8, and 1A9
In vitro študije s človeškimi jetrnimi mikrosomi so pokazale, da ti oksidirani presnovki nastajajo pretežno s CYP1A1, CYP1A2, CYP2C8 ali CYP2C9, febuksostat glukuronid pa nastane pretežno z UGT 1A1, 1A8 in 1A9.
Elimination Febuxostat is eliminated by both hepatic and renal pathways.
10 Izločanje Febuksostat se izloča tako preko jeter kot ledvic.
Following an 80 mg oral dose of 14 C-labeled febuxostat, approximately 49% of the dose was recovered in the urine as unchanged febuxostat (3%), the acyl glucuronide of the active substance (30%), its known oxidative metabolites and their conjugates (13%), and other unknown metabolites (3%).
Po peroralnem odmerku 80 mg 14C febuksostata se je približno 49% odmerka izločilo z urinom, 3% v obliki nespremenjenega febuksostata, 30% v obliki acil- glukuronida učinkovine, 13% v obliki znanih oksidativnih presnovkov, 13% v obliki njihovih konjugatov ter 3% v obliki drugih neznanih presnovkov.
In addition to the urinary excretion, approximately 45% of the dose was recovered in the faeces as the unchanged febuxostat (12%), the acyl glucuronide of the active substance (1%), its known oxidative metabolites and their conjugates (25%), and other unknown metabolites (7%).
Približno 45% odmerka se je izločilo z blatom, 12% v obliki nespremenjenega febuksostata, 1% v obliki acil- glukuronida, 25% v obliki znanih oksidativnih presnovkov in njihovih konjugatov in 7% v obliki drugih neznanih presnovkov.
Special populations Renal insufficiency Following multiple doses of 80 mg of ADENURIC in patients with mild, moderate or severe renal insufficiency, the Cmax of febuxostat did not change, relative to subjects with normal renal function.
Posebne skupine bolnikov Ledvična insuficienca Pri ponavljajočih se odmerkih zdravila ADENURIC 80 mg pri bolnikih z blago, zmerno ali hudo ledvično insuficienco, se vrednost Cmax febuksostata ni spremenila v primerjavi z osebami z normalnim delovanjem ledvic.
The mean total AUC of febuxostat increased by approximately 1.8-fold from 7.5 μ g⋅ h/ ml in the normal renal function group to 13.2 μ g. h/ ml in the severe renal dysfunction group.
Povprečni skupni AUC febuksostata se je povišal za približno 1, 8- krat od 7, 5 μg⋅h/ ml pri skupini oseb z normalnim delovanjem ledvic na 13, 2 μg⋅h/ ml v skupini s hudo motnjo delovanja ledvic.
The Cmax and AUC of active metabolites increased up to 2- and 4-fold, respectively.
Cmax aktivnih presnovkov se je povišala za 2- krat in AUC za 4- krat.
Hepatic impairment Following multiple doses of 80 mg of ADENURIC in patients with mild (Child-Pugh Class A) or moderate (Child-Pugh Class B) hepatic impairment, the Cmax and AUC of febuxostat and its metabolites did not change significantly compared to subjects with normal hepatic function.
Okvarjeno delovanje jeter Pri ponavljajočih se odmerkih zdravila ADENURIC 80 mg pri bolnikih z blago (razred A po Child - Pughu) ali zmerno (razred B po Child- Pughu) okvaro jeter se Cmax in AUC febuksostata in njegovih presnovkov nista pomembneje spremenili v primerjavi z osebami z normalnim delovanjem jeter.
No studies have been conducted in patients with severe hepatic impairment (Child- Pugh Class C).
Študij pri bolnikih s hudo okvaro jeter (razred C po Child- Pughu) niso izvedli.
Age There were no significant changes observed in AUC of febuxostat or its metabolites following multiple oral doses of ADENURIC in elderly as compared to younger healthy subjects.
Starost Pri ponavljajočih se peroralnih odmerkih zdravila ADENURIC se pri starostnikih AUC febuksostata ali njegovih presnovkov ni pomembneje spremenila v primerjavi z mlajšimi zdravimi osebami.
Gender Following multiple oral doses of ADENURIC, the Cmax and AUC were 24% and 12% higher in females than in males, respectively.
Spol Pri ponavljajočih se peroralnih odmerkih zdravila ADENURIC sta bili Cmax za 24% in AUC za 12% višji pri ženskah kot pri moških.
No dose adjustment is needed based on gender.
Zato na podlagi spola odmerkov ni potrebno prilagajati.
12 Carcinogenesis, mutagenesis, impairment of fertility In male rats, a statistically significant increase in urinary bladder tumours (transitional cell papilloma and carcinoma) was found only in association with xanthine calculi in the high dose group, at approximately 11 times human exposure.
Karcinogeneza, mutageneza, škodljivo delovanje na plodnost Pri podganjih samcih so opazili statistično pomembno večjo pojavnost tumorjev sečnega mehurja (prehodnocelični papilom in karcinom) samo v povezavi s ksantinskimi kamni pri skupini, ki je bila izpostavljena visokim odmerkom, približno 11- kratni izpostavljenosti človeka.
Febuxostat at oral doses up to 48 mg/ kg/ day was found to have no effect on fertility and reproductive performance of male and female rats.
Ugotovili so, da peroralni odmerki do 48 mg/ kg/ dan febuksostata ne vplivajo na plodnost ali sposobnost razmnoževanja podganjih samcev ali samic.
There was high dose maternal toxicity accompanied by a reduction in weaning index and reduced development of offspring in rats at approximately 4.3 times human exposure.
Visoki odmerki (približno 4, 3- kratna izpostavljenost človeka) so bili toksični za mater, kar je vplivalo tudi na zmanjšanje indeksa odstavljanja in slabši razvoj podganjih mladičev.
Teratology studies, performed in pregnant rats at approximately 4.3 times and pregnant rabbits at approximately 13 times human exposure did not reveal any teratogenic effects.
Študije na brejih podganjih samicah (pri približno 4, 3- kratni izpostavljenosti za človeka) in brejih kunčjih samicah (pri približno 13- kratni izpostavljenosti človeka) niso pokazale teratogenih učinkov.
Tablet core Lactose monohydrate Microcrystalline cellulose Magnesium stearate Hydroxypropylcellulose Croscarmellose sodium Silica, colloidal hydrated
Jedro tablete laktoza monohidrat mikrokristalna celuloza magnezijev stearat hidroksipropilceluloza premreženi natrijev karmelozat koloidni hidratirani silicijev dioksid
Polyvinyl alcohol Titanium dioxide (E171) Macrogols 3350 Talc Iron oxide yellow (E172)
Obloga tablete Opadry II rumena 85F42129, ki vsebuje: polivinil alkohol titanov dioksid (E171) makrogol 3350 smukec rumeni železov oksid (E172)
13 6.4 Special precautions for storage
6. 4 Posebna navodila za shranjevanje
Clear (Aclar/ PVC/ Aluminium) blister of 14 tablets.
Prozorni (Aclar/ PVC/ aluminij) pretisni omot s 14 tabletami.
ADENURIC 80 mg is available in pack sizes of 28 and 84 film-coated tablets.
Zdravilo ADENURIC 80 mg je na voljo v škatlah po 28 in 84 filmsko obloženih tablet.
6.6 Special precautions for disposal
6. 6 Posebni varnostni ukrepi za odstranjevanje
Beaufour Ipsen Pharma 24 rue Erlanger 75781 Paris Cedex 16 France
Beaufour Ipsen Pharma 24 rue Erlanger 75781 Paris Cedex 16 Francija
Each tablet contains 114.75mg of lactose monohydrate
Ena tableta vsebuje 114, 75 mg laktoze monohidrata.
Pale yellow to yellow, film-coated, capsule shaped tablets, engraved with “ 120 ” on one side
Svetlorumene do rumene, filmsko obložene tablete v obliki kapsule, ki imajo na eni strani vtisnjeno oznako » 120 «.
Hepatic impairment The recommended dosage in patients with mild hepatic impairment is 80 mg.
Okvara jeter Priporočeni odmerek pri bolnikih z blago okvaro jeter je 80 mg.
The efficacy and safety of febuxostat has not been studied in patients with severe hepatic impairment (Child Pugh Class C).
Učinkovitosti in varnosti febuksostata pri bolnikih s hudo okvaro jeter (razred C po Child- Pughu) niso raziskovali.
15 Elderly No dose adjustment is required in the elderly (see section 5.2).
Starostniki Pri starostnikih odmerka ni treba prilagajati (glejte poglavje 5. 2).
Children and adolescents As there has been no experience in children and adolescents, the use of febuxostat in such patients is not recommended.
14 Otroci in mladostniki Ker z uporabo pri otrocih in mladostnikih ni izkušenj, uporaba febuksostata pri teh bolnikih ni priporočljiva.
Liver disorders During the phase 3 clinical studies, mild liver function test abnormalities were observed in patients treated with febuxostat (3.5%).
Teofilin Pri uporabi febuksostata pri bolnikih, ki se sočasno zdravijo s teofilinom, je potrebna previdnost.
Liver function test is recommended prior to the
Pri bolnikih, pri katerih se uvaja zdravljenje s febuksostatom, je treba nadzirati koncentracijo teofilina (glejte poglavje 4. 5).
16 initiation of therapy with febuxostat and periodically thereafter based on clinical judgement (see section 5.1).
Kontrola delovanja jeter se priporoča pred začetkom zdravljenja s febuksostatom in nato periodično v skladu s klinično presojo (glejte poglavje 5. 1).
4.5 Interaction with other medicinal products and other forms of interaction
15 4. 5 Medsebojno delovanje z drugimi zdravili in druge oblike interakcij
Colchicine/ indometacin/ hydrochlorothiazide/ warfarin Febuxostat can be co-administered with colchicine or indomethacin with no dose adjustment of febuxostat or the co-administered active substance being necessary.
Kolhicin/ indometacin/ hidroklorotiazid/ varfarin Febuksostat se lahko daje sočasno s kolhicinom ali indometacinom brez prilagoditve odmerka febuksostata ali zdravilne učinkovine, ki se daje hkrati.
17 No dose adjustment is necessary for warfarin when administered with febuxostat.
Prilagoditev odmerka varfarina, če se daje hkrati s febuksostatom, ni potrebna.
4.6 Pregnancy and lactation
16 4. 6 Nosečnost in dojenje
Phase 3 randomised controlled studies In randomised controlled phase 3 clinical studies, > ,1000 patients have been treated with the recommended doses of 80 mg or 120 mg (536 subjects enrolled in a 28 week study and 507 subjects enrolled in a 52 weeks study).
Randomizirane kontrolirane študije 3. faze V randomiziranih kontroliranih kliničnih študijah 3. faze so zdravili > 1. 000 bolnikov s priporočenim odmerkom 80 mg ali 120 mg (536 oseb, udeleženih v 28- tedenski študiji, in 507 oseb, udeleženih v 52- tedenski študiji).
18 The most commonly reported ADRs (investigator assessment) are liver function abnormalities (3.5%), diarrhoea (2.7%), headache (1.8%), nausea (1.7%), rash (1.5%).
Z zdravljenjem povezani neželeni učinki (po oceni raziskovalca), o katerih so najpogosteje poročali, so nenormalnosti delovanja jeter (3, 5%), driska (2, 7%), glavobol (1, 8%), navzea (1, 7%) in izpuščaj (1, 5%).
Cardiac disorders
17 Redki Srčne bolezni palpitacije Bolezni živčevja
19 Musculoskeletal and connective tissue disorders
Bolezni mišično- skeletnega sistema in vezivnega tkiva Presnovne in prehranske motnje
Psychiatric disorders *
Bolezni jeter, žolčnika in žolčevodov Psihiatrične motnje *
Diarrhoea, nausea and vomiting are more frequent in patients concomitantly treated with colchicine ** No serious rashes or severe hypersensitivity reactions were noted in the clinical studies.
Driska, navzea in bruhanje so pogostejši pri bolnikih, ki se sočasno zdravijo s kolhicinom ** V kliničnih študijah niso opazili hudih izpuščajev ali hudih preobčutljivostnih reakcij
These treatment-related events were either not reported or reported at a lower frequency for these doses, in the pivotal Phase 3 studies:
18 (“ patient- years ”) izpostavljenosti), več kot enkrat poročali kot o občasnih.
In each phase 3 pivotal study, ADENURIC demonstrated superior ability to lower and maintain serum uric acid levels compared to allopurinol.
V vsaki ključni študiji 3. faze je zdravilo ADENURIC dokazalo boljšo sposobnost zmanjšanja in vzdrževanja sečne kisline v serumu v primerjavi z alopurinolom.
The primary efficacy endpoint in each study was the proportion of patients whose last 3 monthly serum uric acid levels were < 6.0 mg/ dl (357 µmol/ l).
Primarni opazovani dogodek učinkovitosti v vsaki študiji je bil delež bolnikov, pri katerih je bil nivo sečne kisline v serumu v zadnjih 3 mesecih < 6, 0 mg/ dl (357 µmol/ l).
21 Table 2 summarises the primary efficacy endpoint results:
V tabeli 2 so povzeti izidi primarnih opazovanih dogodkov učinkovitosti:
Table 2 Proportion of Patients with Serum Uric Acid Levels < 6.0 mg/ dl (357µmol/ l) Last Three Monthly Visits
Tabela 2:
Study
Delež bolnikov s koncentracijo sečne kisline v serumu < 6, 0 mg/ dl (357 µmol/ l) Zadnji trije mesečni obiski
Figure 1 Mean Serum Uric Acid Levels Combined Phase 3 Studies
Srednje vrednosti sečne kisline v serumu kombinirane študije 3. faze
22 The APEX Study evaluated efficacy in 40 patients with renal impairment (i. e., baseline serum creatinine > 1.5 mg/ dl and < =2.0 mg/ dl).
Primarni opazovani dogodek v podskupini bolnikov z okvaro delovanja ledvic V študiji APEX je bila ocenjena učinkovitost pri 40 bolnikih z okvaro delovanja ledvic (tj. izhodiščna vrednost kreatinina v serumu > 1, 5 mg/ dl in ≤ 2, 0 mg/ dl).
Two years of data from the Phase 3 Open Label Extension study showed that the maintenance of serum urate levels < 6 mg/ dl (< 357 µmol/ l) resulted in a decrease in the incidence of gout flares with less than 3% of subjects requiring treatment for a flare (i. e. more than 97% of patients did not require treatment for a flare) at Month 16-24.
21 Dveletni podatki odprte podaljšane študije 3. faze so pokazali, da je povzročilo vzdrževanje vrednosti urata v serumu < 6 mg/ dl (< 357 µmol/ l) zmanjšanje pojavnosti izbruhov protina tako, da je bilo treba zaradi izbruha v 16- 24. mesecu zdraviti manj kot 3% bolnikov (tj. več kot 97% bolnikov zaradi izbruha ni bilo treba zdraviti).
In general, febuxostat pharmacokinetic parameters estimated by these analyses are consistent with those obtained 23 from healthy subjects, indicating that healthy subjects are representative for pharmacokinetic/ pharmacodynamic assessment in the patient population with gout.
Na splošno se parametri farmakokinetike febuksostata, ocenjeni v teh analizah, ujemajo s tistimi, ki so jih pridobili pri zdravih osebah, kar kaže, da so zdrave osebe dovolj za oceno farmakokinetike/ farmakodinamike pri bolnikih s protinom.
Metabolism Febuxostat is extensively metabolized by conjugation via uridine diphosphate glucuronosyltransferase (UDPGT) enzyme system and oxidation via the cytochrome P450 (CYP) system.
Presnova Večji del presnove febuksostata poteka s konjugacijo prek encimskega sistema uridil difosfat glukuroniltransferaze (UDPGT) in z oksidacijo s citokromi P450 (CYP).
Elimination Febuxostat is eliminated by both hepatic and renal pathways.
22 Izločanje Febuksostat se izloča tako preko jeter kot ledvic.