natgillin/translations-raw huggingface dataset:
Pregnancy There are no adequate data on the use of azacitidine in pregnant women.
Nosečnost Ni zadostnih podatkov o uporabi azacitidina pri nosečnicah.
Studies in mice have shown reproductive toxicity (see section 5.3).
Študije na miših so pokazale vpliv na sposobnost razmnoževanja (glejte poglavje 5. 3).
Men and women of childbearing potential must use effective contraception during and up to 3 months after treatment.
Moški in ženske v rodni dobi morajo uporabljati učinkovito kontracepcijo med zdravljenjem in do 3 mesece po njem.
Lactation It is not known whether azacitidine or its metabolites are excreted in human milk.
Dojenje Ni znano, ali se azacitidin ali njegovi presnovki izločajo v materino mleko.
Fertility There are no human data on the effect of azacitidine on fertility.
Plodnost Ni podatkov o vplivu azacitidina na plodnost pri ljudeh.
In animals, adverse effects of azacitidine on male fertility have been documented (see section 5.3).
Pri živalih so dokumentirani neželeni učinki azacitidina na plodnost samcev (glejte poglavje 5. 3).
Men should be advised not to father a child while receiving treatment and must use effective contraception during and up to 3 months after treatment.
Moške je treba opozoriti, da naj v času zdravljenja ne zaplodijo otroka in morajo med zdravljenjem in do 3 mesece po njem uporabljati učinkovito kontracepcijo.
Patients should be advised that they may experience undesirable effects such as fatigue, during treatment.
Bolnike je treba opozoriti, da se lahko med zdravljenjem pojavijo neželeni učinki, kot je utrujenost.
Therefore, caution should be recommended when driving a car or operating machines.
Zato se pri vožnji avtomobila ali upravljanju s stroji priporoča previdnost.
Adverse reactions considered to be possibly or probably related to the administration of Vidaza have occurred in 97% of patients.
Neželeni učinki, ki so morda ali verjetno povezani z zdravljenjem z zdravilom Vidaza, so se pojavili pri 97% bolnikov.
5 The most commonly reported adverse reactions with azacitidine treatment were haematological reactions (71.4%) including thrombocytopenia, neutropenia and leukopenia (usually Grade 3-4), gastrointestinal events (60.6%) including nausea, vomiting (usually Grade 1-2) or injection site reactions (77.1%; usually Grade 1-2).
Neželeni učinki, o katerih so najpogosteje poročali v zvezi z zdravljenjem z azacitidinom, so bile hematološke reakcije (71, 4%), vključno s trombocitopenijo, nevtropenijo in levkopenijo (običajno 3. - 4. stopnje), prebavni dogodki (60, 6%), vključno z navzejo, bruhanjem (običajno 1. - 2. stopnje), ali reakcije na mestu injiciranja (77, 1%; običajno 1. - 2. stopnje).
The most common serious adverse reactions (> 2%) noted from the pivotal study (AZA PH GL 2003 CL 001) and also reported in the supporting studies (CALGB 9221 and CALGB 8921) included febrile neutropenia (8.0%) and anaemia (2.3%).
Najbolj pogosta resna neželena učinka (> 2%), opažena v osrednji študiji (AZA PH GL 2003 CL 001) in o katerih so poročali tudi v podpornih študijah (CALGB 9221 in CALGB 8921), sta bila febrilna nevtropenija (8, 0%) in anemija (2, 3%).
Other less frequently reported serious adverse reactions (< 2%) included neutropenic sepsis, pneumonia, thrombocytopenia and haemorrhagic events (e. g. cerebral haemorrhage).
Drugi, manj pogosto poročani resni neželeni učinki (< 2%) so zajemali nevtropenično sepso, pljučnico, trombocitopenijo in hemoragične dogodke (npr. možganska krvavitev).
The table below contains the adverse reactions for which a causal relationship with azacitidine treatment could reasonably be established.
Spodnja tabela vključuje neželene učinke, za katere je bilo mogoče potrditi povezavo z zdravljenjem z azacitidinom.
Frequencies given are based on the observations during the pivotal clinical study or two supporting clinical studies.
Navedene pogostnosti so ugotovljene na podlagi opazovanj v osrednji klinični študiji ali dveh podpornih kliničnih študijah.
Frequencies are defined as: very common (≥ 1/ 10), common (≥ 1/ 100 to < 1/ 10); uncommon (≥ 1/ 1,000 to < 1/ 100); rare (≥ 1/ 10,000 to < 1/ 1,000); very rare (< 1/ 10,000); not known (cannot be estimated from the available data).
Pogostnosti pojavov so opredeljene kot: zelo pogosti (≥ 1/ 10), pogosti (≥ 1/ 100 do < 1/ 10); občasni (≥ 1/ 1. 000 do < 1/ 100); redki (≥ 1/ 10. 000 do < 1/ 1. 000); zelo redki (< 1/ 10. 000), neznani (ni mogoče oceniti iz razpoložljivih podatkov).
Infections and infestations
pljučnica,
pneumonia, nasopharyngitis
nevtropenična sepsa,
neutropenic sepsis, upper respiratory tract infection, urinary tract infection, sinusitis, pharyngitis, rhinitis, herpes simplex
parazitske bolezni
Blood and lymphatic system disorders
nazofaringitis
febrile neutropenia, neutropenia, leukopenia, thrombocytopenia, anaemia
okužbe zgornjih dihalnih poti, okužba sečil, sinuzitis, faringitis, rinitis, herpes simpleks
bone marrow failure, pancytopenia
Bolezni krvi in
Immune system disorders
febrilna nevtropenija,
hypersensitivity reactions
odpoved kostnega mozga,
Metabolism and nutrition disorders
limfatičnega sistema Bolezni imunskega sistema
anorexia
nevtropenija, levkopenija, trombocitopenija, anemija
hypokalemia
pancitopenija
Psychiatric disorders
preobčutljivostne reakcije
confusional state, anxiety, insomnia
Presnovne in prehranske motnje Psihiatrične motnje
Nervous system disorders Eye disorders
anoreksija
dizziness, headache
hipokalemija stanje zmedenosti, anksioznost, nespečnost
intracranial haemorrhage, lethargy eye haemorrhage, conjunctival haemorrhage
Bolezni živčevja Očesne bolezni Žilne bolezni
Vascular disorders
omotičnost, glavobol
hypertension, hypotension, haematoma
intrakranialna krvavitev, letargija očesna krvavitev, krvavitev očesne veznice hipertenzija, hipotenzija, hematom
dyspnoea exertional, pharyngolaryngeal pain
dispneja ob naporu, faringolaringealna bolečina
6 System Organ Class
6 Organski sistem
diarrhoea, vomiting, constipation, nausea, abdominal pain
zaprtje, navzeja, bolečine v trebuhu
gastrointestinal haemorrhage, haemorrhoidal haemorrhage, stomatitis, gingival bleeding, dyspepsia
hemoroidna krvavitev, stomatitis, krvavitev dlesni, dispepsija
petechiae, pruritus, rash, ecchymosis
petehija, pruritus, osip,
purpura, alopecia, erythema, rash macular
purpura, alopecija, eritem,
myalgia, musculoskeletal pain
mialgija, bolečine v mišicah in kosteh
Renal and urinary disorders
hematurija Bolezni sečil utrujenost, pireksija, mesto vboda: modrice, Splošne težave in spremembe na
haematuria
bolečine v prsih,
General disorders and administration site conditions
hematom, induracija, osip,
fatigue, pyrexia, chest pain, injection site erythema, injection site pain, injection site reaction (unspecified)
mestu aplikacije
injection site: bruising, haematoma, induration, rash, pruritus, inflammation, discoloration, nodule and haemorrhage. malaise
eritem na mestu vboda,
Investigations
pruritus, vnetje,
weight decreased
Preiskave
Haematologic adverse reactions The most commonly reported adverse reactions associated with azacitidine treatment were haematological including thrombocytopenia, neutropenia and leukopenia, and were usually Grade 3 or 4.
Hematološki neželeni učinki Neželeni učinki, o katerih so najpogosteje poročali v zvezi z zdravljenjem z azacitidinom, so bili hematološki, vključno s trombocitopenijo, nevtropenijo in levkopenijo.
Most haematological adverse reactions were managed by routine monitoring of complete blood counts and delaying azacitidine administration in the next cycle, prophylactic antibiotics and/ or growth factor support (e. g.
Večino hematoloških neželenih učinkov so obvladovali z rutinskim spremljanjem kompletne krvne slike in preložitvijo zdravljenja z azacitidinom v naslednjem ciklu, s profilaktičnim dajanjem antibiotikov in/ ali podporo rastnih dejavnikov (npr.
G-CSF) for neutropenia and transfusions for anaemia or thromobocytopenia as required.
G- CSF) za nevtropenijo in s transfuzijami za anemijo ali tromobocitopenijo, kot je potrebno.
Infections Myelosupression may lead to neutropenia and an increased risk of infection.
Okužbe Mielosupresija lahko povzroči nevtropenijo in poveča tveganje za okužbe.
Serious adverse reactions such as neutropenic sepsis (0.8%) and pneumonia (2.5%) were reported in patients receiving azacitidine.
Pri bolnikih, ki so prejemali azacitidin, so poročali o resnih neželenih učinkih, kot sta nevtropenična sepsa (0, 8%) in pljučnica (2, 5%).
Infections may be managed with the use of anti-infectives plus growth factor support (e. g.
Okužbe se da obvladovati z uporabo zdravil, ki preprečujejo okužbe, in s podporo rastnih dejavnikov (npr.
G-CSF) for neutropenia.
G- CSF) za nevtropenijo.
Bleeding Bleeding may occur with patients receiving azacitidine.
Krvavitve Krvavitev se lahko pojavi pri bolnikih, ki prejemajo azacitidin.
Serious adverse reactions such as gastrointestinal haemorrhage (0.8%) and intracranial haemorrhage (0.5%) have been reported.
Poročali so o resnih neželenih učinkih, kot sta krvavitev v prebavila (0, 8%) in intrakranialna krvavitev (0, 5%).
Patients should be monitored for signs and symptoms of bleeding, particularly those with pre-existing or treatment-related thrombocytopenia.
Pri bolnikih je treba spremljati znake in simptome krvavitev, še zlasti pri tistih, ki imajo obstoječo ali z zdravljenjem povezano trombocitopenijo.
Hypersensitivity Serious hypersensitivity reactions (0.25%) have been reported in patients receiving azacitidine.
Preobčutljivost Pri bolnikih, ki so se zdravili z azacitidinom, so poročali o resnih preobčutljivostnih reakcijah (0, 25%).
Skin and subcutaneous tissue adverse reactions The majority of skin and subcutaneous adverse reactions were associated with the injection site.
S kožo in podkožjem povezani neželeni učinki Večina neželenih učinkov, povezanih s kožo in podkožjem, se je nanašala na mesto vboda.
The majority of adverse reactions occurred during the first
Noben od teh neželenih učinkov ni bil vzrok za začasno ali trajno prekinitev zdravljenja z azacitidinom ali zmanjšanja odmerka azacitidina v osrednji študiji.
7 2 cycles and tended to decrease with subsequent cycles.
Večina neželenih učinkov se je pojavila v prvih 2 ciklih in se je v naslednjih ciklih manjšala.
Subcutaneous adverse reactions such as injection site rash/ inflammation/ pruritus, rash, erythema and skin lesion may require management with concomitant medicinal products, such as antihistamines, corticosteroids and non-steroidal anti- inflammatory drugs (NSAIDs).
Neželeni učinki, povezani s podkožjem, kot so osip/ vnetje/ pruritus na mestu vboda, osip, eritem in lezije kože, je morda treba zdraviti s sočasnim jemanjem zdravil, kot so antihistaminiki, kortikosteroidi in nesteroidna protivnetna zdravila (NSAID).
Gastrointestinal adverse reactions The most commonly reported gastrointestinal adverse reactions associated with azacitidine treatment included constipation, diarrhoea, nausea and vomiting.
7 S prebavili povezani neželeni učinki Najbolj pogosti neželeni učinki, povezani s prebavili, o katerih so poročali v zvezi z zdravljenjem z azacitidinom, so vključevali zaprtje, drisko, navzejo in bruhanje.
These adverse reactions were managed symptomatically with anti-emetics for nausea and vomiting; antidiarrhoeals for diarrhoea, and laxatives and/ or stool softeners for constipation.
Ti neželeni učinki so bili zdravljeni simptomatsko z antiemetiki za navzejo in bruhanje; z zdravili proti driski za drisko ter z odvajali in/ ali mehčali za blato pri zaprtju.
A patient experienced diarrhoea, nausea, and vomiting after receiving a single intravenous dose of approximately 290 mg/ m2, almost 4 times the recommended starting dose.
Bolnik je po enem intravenskem odmerku s približno 290 mg/ m2, kar je skoraj 4- kratni priporočeni začetni odmerek, dobil drisko, bilo mu je slabo in je bruhal.
Antineoplastic agent, Pyrimidine analogues; ATC code:
Antineoplastična zdravila, analogi pirimidina; oznaka ATC:
Mechanism of action Azacitidine is believed to exert its antineoplastic effects by multiple mechanisms including cytotoxicity on abnormal haematopoietic cells in the bone marrow and hypomethylation of DNA.
Mehanizem delovanja Predvideva se, da izvirajo antioneoplastični učinki azacitidina iz več mehanizmov, vključno s citotoksičnostjo za nenormalne hematopoetske celice v kostnem mozgu in hipometilacijo DNA.
DNA hypomethylation of aberrantly methylated genes involved in normal cell cycle regulation, differentiation and death pathways may result in gene re-expression and restoration of cancer- suppressing functions to cancer cells.
Hipometilacija DNA aberantnih metiliranih genov, ki sodelujejo pri regulaciji normalnega celičnega cikla, diferenciaciji in poti smrti, lahko povzroči ponovno izražanje genov in obnovo funkcij supresije raka za rakaste celice.
Clinical efficacy and safety The efficacy and safety of Vidaza were studied in an international, multicenter, controlled, open-label, randomised, parallel-group, Phase 3 comparative study (AZA PH GL 2003 CL 001) in patients with: intermediate-2 and high-risk MDS according to the International Prognostic Scoring System (IPSS), refractory anaemia with excess blasts (RAEB), refractory anaemia with excess blasts in transformation (RAEB-T) and modified chronic myelomonocytic leukaemia (mCMML) according to the French American British (FAB) classification system.
MDS z vmesno stopnjo 2 in visoko stopnjo tveganja po Mednarodnem prognostičnem sistemu ocenjevanja (IPSS), refraktorno anemijo s presežkom blastov (RAEB - refractory anaemia with excess blasts), refraktorno anemijo s presežkom blastov v transformaciji (RAEB- T - refractory anaemia with excess blastsin transformation) in modificirano kronično mielomonocitno levkemijo (mKMMoL) po francosko- ameriško- britanskem (FAB) razvrstitvenem sistemu.
RAEB-T patients (21-30% blasts) are now considered to be AML patients under the current WHO classification system.
Bolniki z RAEB- T (21- 30% blastov) se sedaj obravnavajo kot bolniki z AML po sedanjem razvrstitvenem sistemu SZO.
Azacitidine plus best supportive care (BSC) (n = 179) was compared to conventional care regimens (CCR).
Azacitidin z najboljšo podporno oskrbo (NPO) (n = 179) je bil primerjan z običajnimi režimi oskrbe (CCR - conventional care regimens).
CCR consisted of BSC alone (n = 105), low-dose cytarabine plus BSC (n = 49) or standard induction chemotherapy plus BSC (n = 25).
CCR so obsegali samo NPO (n = 105), nizek odmerek citarabina in NPO (n = 49) ali standardno indukcijsko kemoterapijo in NPO (n = 25).
Patients were pre-selected by their physician to 1 of the 3 CCR prior to randomisation.
Zdravniki so bolnike pred naključno razvrstitvijo razporedili v eno od teh treh skupin CCR.
Patients received this pre-selected regimen if not randomised to Vidaza.
Bolniki so bili zdravljeni na predhodno izbrani način, če niso bili naključno razvrščeni v skupino, ki je prejemala zdravilo Vidaza.
The primary endpoint of the study was overall survival.
Primarna končna točka študije je bila celokupno preživetje.
Vidaza was administered at a subcutaneous dose of 75 mg/ m2 daily for 7 days, followed by a rest period of 21 days (28-day treatment cycle) for a median of 9 cycles
Bolniki so zdravilo Vidaza prejemali kot podkožni (s. c.) odmerek 75 mg/ m2 dnevno 7 dni, ki jim sledi 21- dnevno obdobje mirovanja (28 - dnevni cikel zdravljenja), z mediano 9 ciklov (razpon = 1- 39) in povprečjem 10, 2 ciklov.
Within the Intent to Treat population (ITT), the median age was 69 years (range 38 to 88 years).
V populaciji bolnikov, ki so jo nameravali zdraviti (namera zdravljenja = NZ), je bila mediana starosti 69 let (razpon 38 do 88 let).
In the ITT analysis of 358 patients (179 azacitidine and 179 CCR), Vidaza treatment was associated with a median survival of 24.46 months versus 15.02 months for those receiving CCR treatment, a difference of 9.4 months, with a stratified log-rank p-value of 0.0001.
8 V analizi skupine 358 bolnikov NZ (179 azacitidin in 179 CCR), je bilo zdravljenje z zdravilom Vidaza povezano z mediano preživetja 24, 46 mesecev v primerjavi s 15, 02 meseca v skupini, zdravljeni s CCR, kar predstavlja 9, 4 mesecev razlike, s stratificirano log- rank p- vrednostjo 0, 0001.
The hazard ratio for the treatment effect was 0.58 (95% CI:
Razmerje ogroženosti za ta učinek zdravljenja je bilo 0, 58 (95% IZ:
The two-year survival rates were 50.8% in patients receiving azacitidine versus 26.2% in patients receiving CCR (p < 0.0001).
Dvoletna stopnja preživetja je bila 50, 8% pri bolnikih, zdravljenih z azacitidinom, v primerjavi s 26, 2% pri bolnikih v skupini CCR (p < 0, 0001).
Log-Rank p = 0.0001 HR = 0.58 [95% CI:
Log- rank p = 0, 0001 RO 0, 58 [95% IZ:
0.43-0.77] Deaths:
0, 43 - 0, 77] Smrti:
AZA = 82, CCR = 113 Proportion Surviving
AZA = 82, CCR = 113 Sorazmerno preživetje
Time (months) from Randomization # at risk
Čas (meseci) od naključne razvrstitve # ob tveganju
AZA = azacitidine; CCR = conventional care regimens; CI = confidence interval; HR = hazard ratio
AZA = azacitidin; CCR = običajni režimi zdravljenja; IZ = interval zaupanja; RO = razmerje ogroženosti
The survival benefits of Vidaza were consistent regardless of the CCR treatment option (BSC alone, low-dose cytarabine plus BSC or standard induction chemotherapy plus BSC) utilised in the control arm.
Izboljšanje preživetja z zdravilom Vidaza je bilo dosledno, ne glede na izbrano skupino CCR (samo NPO, nizek odmerek citarabina in NPO ali standardna indukcijska kemoterapija in NPO) v kontrolni skupini.
Vidaza treatment was associated with a median time to death or transformation to AML of 13.0 months versus 7.6 months for those receiving CCR treatment, an improvement of 5.4 months with a stratified log-rank p-value of 0.0025.
Zdravljenje z zdravilom Vidaza je bilo povezano z mediano časa do smrti ali pretvorbo v AML 13, 0 mesecev v primerjavi s 7, 6 meseci za bolnike, zdravljene s CCR, kar predstavlja izboljšanje za 5, 4 mesece s stratificirano log- rank p- vrednostjo 0, 0025.
Of the patients in the azacitidine group who were RBC transfusion dependent at baseline, 45.0% of these patients became RBC transfusion independent during the treatment period, compared with 11.4% of the patients in the combined CCR groups (a statistically significant (p < 0.0001) difference of 33.6% (95% CI:
Pri bolnikih v skupini z azacitidinom, ki so bili na izhodišču odvisni od transfuzije eritrocitov, jih je 45, 0% postalo neodvisnih od transfuzije eritrocitov med obdobjem zdravljenja, v primerjavi z 11, 4% bolnikov v kombiniranih skupinah CCR (statistično značilna (p < 0, 0001) razlika 33, 6% (95% IZ:
9 Response was assessed by the investigator or by the Independent Review Committee (IRC).
9 Odziv je ocenil raziskovalec ali neodvisni odbor za pregled (Independent Review Committee - IRC).
Overall response (complete remission [CR] + partial remission [PR]) as determined by the investigator was 29% in the azacitidine group and 12% in the combined CCR group (p = 0.0001).
Celokupni odziv (popolna remisija [CR] + delna remisija [PR]), ki ga je ugotovil raziskovalec, je bil 29% v skupini z azacitidinom in 12% v kombinirani skupini CCR (p = 0, 0001).
Overall response (CR + PR) as determined by the IRC in AZA PH GL 2003 CL 001 was 7% (12/ 179) in the azacitidine group compared with 1% (2/ 179) in the combined CCR group (p = 0.0113).
Celokupni odziv (CR + PR), ki ga je ugotovil IRC v študiji AZA PH GL 2003 CL 001, je bil 7% (12/ 179) v skupini z azacitidinom v primerjavi z 1% (2/ 179) v kombinirani skupini CCR (p = 0, 0113).
The differences between the IRC and investigator assessments of response were a consequence of the International Working Group (IWG) criteria requiring improvement in peripheral blood counts and maintenance of these improvements for a minimum of 56 days.
Razlike med ocenami odziva IRC in raziskovalca so bile posledica kriterijev Mednarodne delovne skupine (IWG - International Working Group), ki so zahtevali izboljšanje vrednosti periferne krvi in vzdrževanje teh izboljšanj vsaj 56 dni.
A survival benefit was also demonstrated in patients that had not achieved a complete/ partial response following azacitidine treatment.
Tudi pri bolnikih, kjer ni bil dosežen popolni/ delni odziv po zdravljenju z azacitidinom, je bilo dokazano izboljšanje preživetja.
Haematological improvement (major or minor) as determined by the IRC was achieved in 49% of patients receiving azacitidine compared with 29% of patients treated with combined CCR (p < 0.0001).
Hematološko izboljšanje (bistveno ali manjše), določeno po IRC, je bilo doseženo pri 49% bolnikov, ki so prejemali azacitidin, v primerjavi z 29% bolnikov, ki so bili zdravljeni v kombinirani skupini CCR (p < 0, 0001).
Minor cytogenetic response was statistically significantly (p = 0.0015) higher in the azacitidine group (34%) compared with the combined CCR group (10%).
Manjši citogenetski odziv je bil statistično značilno (p = 0, 0015) višji v skupini z azacitidinom (34%) v primerjavi s kombinirano skupino CCR (10%).
The pharmacokinetics of azacitidine were studied following single 75 mg/ m2 doses given by subcutaneous and intravenous administration.
Farmakokinetika azacitidina je bila preučena po enojnem odmerku 75 mg/ m2, apliciranem podkožno in intravensko.
Absorption Azacitidine was rapidly absorbed after subcutaneous administration with peak plasma azacitidine concentrations of 750 ± 403 ng/ ml occurring at 0.5 h (the first sampling point) after dosing.
Absorpcija Azacitidin se po podkožnem apliciranju hitro absorbira z najvišjo koncentracijo azacitidina v plazmi 750 ± 403 ng/ ml, ki se pojavi 0, 5 ure (prva točka vzorčenja) po apliciranju.
The absolute bioavailability of azacitidine after subcutaneous relative to intravenous administration was approximately 89% based on area under the curve (AUC).
Absolutna biološka razpoložljivost azacitidina, apliciranega podkožno, v primerjavi z intravensko apliciranim azacitidinom je bila približno 89%, merjeno na površini pod krivuljo (area under the curve - AUC).
Distribution Following intravenous administration, the mean volume of distribution was 76 ± 26 l, and systemic clearance was 147 ± 47 l/ h.
Porazdelitev Po intravenskem apliciranju je bil povprečni porazdelitveni volumen 76 ± 26 l in sistemski očistek 147 ± 47 l/ h.
Metabolism Based on in vitro data, azacitidine metabolism does not appear to be mediated by cytochrome P450 isoenzymes (CYPs), UDP-glucuronosyltransferases (UGTs), sulfotransferases (SULTs), and glutathione transferases (GSTs).
Presnova Na podlagi podatkov in vitro kaže, da na presnovo azacitidina ne vplivajo izoencimi citokroma P450 (CYPs), glukuronoziltransferaze UDP (UGTs), sulfotransferaze (SULTs) in glutation transferaze (GSTs).
Metabolism of azacitidine is by spontaneous hydrolysis and by deamination mediated by cytidine deaminase.
Presnova azacitidina poteka s spontano hidrolizo in z deaminacijo, ki jo katalizira citidin deaminaza.
In human liver S9 fractions, formation of metabolites was independent of NADPH implying any metabolism would be catalysed by cytosolic enzymes.
V S9 frakcijah človeških jeter je bilo nastajanje presnovkov neodvisno od NADPH, kar pomeni, da presnove ne katalizirajo citosolni encimi.
In vitro studies of azacitidine with cultured human hepatocytes indicate that at concentrations of 1.0 µM to 100 µM (i. e. up to approximately 30-fold higher than clinically achievable concentrations), azacitidine does not induce cytochrome P450 isoenzymes (CYP) 1A2, 2C19, or 3A4 or 3A5.
Študije azacitidina in vitro z gojenimi humanimi hepatociti kažejo, da pri koncentraciji 1, 0 µM do 100 µM (t. j. do približno 30- krat višje kot klinično dosegljiva koncentracija) azacitadin ne inducira izoencimov citokroma P450 (CYP) 1A2, 2C19, 3A4 ali 3A5.
In a study to assess inhibition of a series of P450 isoenzymes (CYP 1A2, 2C9, 2C19, 2D6, 2E1 and 3A4) incubated with 100 µM azacitidine, IC50 values could not be determined, therefore, enzyme inhibition by azacitidine at clinically achievable plasma concentrations is unlikely.
V študiji za ocenitev zaviranja vrste izoencimov P450 (CYP 1A2, 2C9, 2C19, 2D6, 2E1 in 3A4), inkubiranih z 100 µM, vrednosti azacitidina IC50 ni bilo mogoče določiti, zato ni verjetno, da bi azacitidin zaviral encime pri klinično dosegljivih koncentracijah v plazmi.