natgillin/translations-raw huggingface dataset:
Metabolism and nutrition disorders
anoreksija
hypophosphataemia
dehidracija
anorexia
Psihiatrične motnje
hyponatraemia dehydration
depresija
depression
periferna senzorna nevropatija
Nervous system disorders Ear and labyrinth disorders
reverzibilna posteriorna levkoencefalopatija *
peripheral sensory neuropathy tinnitus
Ušesne bolezni, vključno z motnjami labirinta
reversible posterior leukoencephalopathy*
zvonjenje v ušesih
myocardial ischaemia and infarction* congestive heart failure*
miokardna ishemija in infarkt * kongestivno srčno popuščanje *
haemorrhage (inc. gastrointestinal*, respiratory tract* and cerebral haemorrhage*) hypertension
krvavitev (vključno s krvavitvami v prebavilih * in dihalih * ter možganske krvavitve) * hipertenzija
hypertensive crisis*
hipertenzijske krize *
rhinorrhoea
rinoreja
Gastrointestinal disorders Hepatobiliary disorders
Bolezni prebavil
diarrhoea nausea vomiting
gastroezofagealni
constipation stomatitis (including dry mouth and glossodynia) dyspepsia dysphagia
stomatitis (suha usta in glosodinija) dispepsija disfagija
gastro oesophageal reflux disease pancreatitis gastritis gastrointestinal perforations* increase in bilirubin and jaundice cholecystitis cholangitis
refluks vnetje trebušne slinavke gastritis gastrointestinalne perforacije *
8 System organ class
8 Organski sistem Bolezni jeter, žolčnika in žolčevodov
≥ 1/ 1,000, < 1/ 100
Občasno ≥ 1/ 1000, < 1/ 100 zvečanje vrednosti bilirubina in zlatenica holecistitis holangitis
Skin and subcutaneous tissue disorders
izpuščaji Bolezni kože in podkožja
rash alopecia hand foot syndrome** erythema pruritus
multiformni eritem
dry skin dermatitis exfoliative acne skin desquamation
dermatitis
eczema erythema multiforme minor keratoacanthoma/ squamous cell cancer of the skin
ploščatocelični karcinom kože
arthralgia myalgia
erekcijske motnje
Renal and urinary disorders
Splošne težave in
renal failure
slabotnost
Reproductive system and breast disorders
bolečine (v ustih,
erectile dysfunction
zvišana telesna
gynaecomastia
aplikacije
General disorders and administration site conditions
trebuhu in kosteh,
fatigue pain (including mouth, abdominal, bone, tumour pain and headache)
bolečina v predelu tumorja in glavobol)
asthenia fever influenza like illness
gripi podobno bolezensko stanje
increased amylase increased lipase
zvečanje vrednosti
weight decreased transient increase in transaminases
mase prehodno zvečanje vrednosti transaminaz
transient increase in blood alkaline phosphatase, INR abnormal, prothrombin level abnormal
vrednosti alkalne fosfataze v krvi nenormalna vrednost INR nenormalna vrednost protrombina
* The adverse reactions may have a life-threatening or fatal outcome. ** hand foot syndrome corresponds to palmar plantar erythrodysaesthesia syndrome in MedDRA
* Neželeni učinki lahko ogrozijo življenje ali povzročijo smrt ** Sindrom dlani in podplatov ustreza sindromu palmarno- plantarne eritrodisestezije po MedDRA.
Laboratory test abnormalities Increased lipase and amylase were very commonly reported.
Nenormalne vrednosti laboratorijskih preiskav Zelo pogosto so poročali o zvečanih vrednostih lipaze in amilaz.
CTCAE Grade 3 or 4 lipase elevations occurred in 11% and 9% of patients in the Nexavar group in study 1 (RCC) and study 3 (HCC), respectively, compared to 7% and 9% of patients in the placebo group.
V študiji 1 (karcinom ledvičnih celic) so se vrednosti lipazezvečale na 3. ali 4. stopnjo CTCAE pri 11% prejemnikov Nexavarja in 7% prejemnikov placeba, v študiji 3 (karcinom jetrnih celic) pa pri 9% prejemnikov Nexavarja in 9% prejemnikov placeba.
CTCAE Grade 3 or 4 amylase elevations were reported in 1% and 2% of patients in the Nexavar group in study 1 and study 3, respectively, compared to 3% of patients in each placebo group.
Vrednosti amilaz so se v študiji 1 zvečale na 3. ali 4. stopnjo CTCAE pri 1% prejemnikov Nexavarja in pri 3% prejemnikov placeba, v študiji 3 pa pri 2% prejemnikov Nexavarja in 3% prejemnikov placeba.
Clinical pancreatitis was reported in 2 of 451 Nexavar treated patients (CTCAE Grade 4) in study 1, 1 of 297 Nexavar treated patients in study 3 (CTCAE Grade 2), and 1 of 451 patients (CTCAE Grade 2) in the placebo group in study 1.
Klinični pankreatitis se je v študiji 1 pojavil pri dveh od 451 bolnikov, ki so dobivali Nexavar (4. stopnje po CTCAE), v študiji 3 pri enem od 297 bolnikov, ki so dobivali Nexavar (2. stopnje po CTCAE), in v študiji 1 pri enem od 451 bolnikov, ki so prejemali placebo (2. stopnje po CTCAE).
Hypophosphataemia was a very common laboratory finding, observed in 45% and 35% of Nexavar treated patients compared to 12% and 11% of placebo patients in study 1 and study 3, respectively.
9 Laboratorijsko so zelo pogosto ugotovili hipofosfatemijo: v študiji 1 se je pojavila pri 45% prejemnikov Nexavarja in 12% prejemnikov placeba, v študiji 3 pa pri 35% prejemnikov Nexavarja in 11% prejemnikov placeba.
CTCAE Grade 3 hypophosphataemia (1 – 2 mg/ dl) in study 1 occurred in 13% of Nexavar treated patients and 3% of patients in the placebo group, in study 3 in 11% of Nexavar treated patients and 2% of patients in the placebo group.
Hipofosfatemija 3. stopnje po CTCAE (1 do 2 mg/ dl) se je v študiji 1 pojavila pri 13% prejemnikov Nexavarja in 3% prejemnikov placeba, v študiji 3 pa pri 11% prejemnikov Nexavarja in 2% prejemnikov placeba.
There were no cases of CTCAE Grade 4 hypophosphataemia (< 1 mg/ dl) reported in either Nexavar or placebo patients in study 1, and 1 case in the placebo group in study 3.
V študiji 1 v nobeni skupini bolnikov ni bilo hipofosfatemije 4. stopnje po CTCAE (< 1 mg/ dl), v študiji 3 pa se je pojavila pri 1 bolniku v skupini, ki je prejemala placebo.
The aetiology of hypophosphataemia associated with Nexavar is not known.
Etiologija hipofosfatemije, povezane z uporabo Nexavara, ni znana.
CTCAE Grade 3 or 4 laboratory abnormalities occurring in ≥ 5% of Nexavar treated patients included lymphopenia and neutropenia.
Med laboratorijskimi nepravilnostmi 3. ali 4. stopnje po CTCAE, ki so se pojavile pri ≥ 5% bolnikov, zdravljenih z Nexavarjem, sta bili limfopenija in nevtropenija.
The highest dose of sorafenib studied clinically is 800 mg twice daily.
Pri prevelikem odmerjanju z Nexavarom specifičnega zdravljenja ni. V kliničnih preskušanjih je bil največji odmerek sorafeniba 800 mg dvakrat na dan.
The adverse events observed at this dose were primarily diarrhoea and dermatological events.
Neželeni učinki, ki so se pojavili po zaužitju tolikšnega odmerka, so bili predvsem driska in kožne spremembe.
In the event of suspected overdose Nexavar should be withheld and supportive care instituted where necessary.
V primeru suma na preveliko odmerjanje je treba zdravljenje z Nexavarom prekiniti in uvesti ustrezno podporno zdravljenje, če je potrebno.
Protein kinase inhibitors, ATC code:
Farmakoterapevtska skupina: zaviralec proteinkinaze, oznaka ATC:
Sorafenib is a multikinase inhibitor which has demonstrated both anti-proliferative and anti- angiogenic properties in vitro and in vivo.
Sorafenib je multikinazni zaviralec, ki in vitro ter in vivo deluje antiproliferacijsko in antiangiogeno.
Mechanism of action and pharmacodynamic effects Sorafenib is a multikinase inhibitor that decreases tumour cell proliferation in vitro.
Mehanizen delovanja in farmakodinamični učinki Sorafenib je multikinazni zaviralec, ki zmanjša proliferacijo tumorske celice in vitro.
Sorafenib inhibits the activity of targets present in the tumour cell (CRAF, BRAF, V600E BRAF, c-KIT, and FLT-3) and in the tumour vasculature (CRAF, VEGFR-2, VEGFR-3, and PDGFR-ß).
Sorafenib zavira dejavnost različnih tarč v tumorski celici (CRAF, BRAF, V600E BRAF, c- KIT in FLT- 3) in tumorskem žilju (CRAF, VEGFR- 2, VEGFR- 3 in PDGFR- ß).
RAF kinases are serine/ threonine kinases, whereas c-KIT, FLT-3, VEGFR-2, VEGFR-3, and PDGFR-ß are receptor tyrosine kinases.
Kinaze RAF so serin/ treonin kinaze, medtem ko so c- KIT, FLT- 3, VEGFR- 2, VEGFR- 3 in PDGFR- ß receptorji tirozinkinaze.
The clinical safety and efficacy of Nexavar have been studied in patients with hepatocellular carcinoma (HCC) and in patients with advanced renal cell carcinoma (RCC).
Klinična učinkovitost Klinično varnost in učinkovitost Nexavarja so raziskali pri bolnikih s karcinomom jetrnih celic in bolnikih z napredovalim karcinomom ledvičnih celic.
Hepatocellular carcinoma Study 3 (study 100554) was a Phase III, international, multi-centre, randomised, double blind, placebo-controlled study in 602 patients with hepatocellular carcinoma.
10 Karcinom jetrnih celic Študija 3 (študija 100554) je bila mednarodna, multicentrična, randomizirana, dvojno slepa, s placebom kontrolirana študija III. faze pri 602 bolnikih s karcinomom jetrnih celic.
Demographics and baseline disease characteristics were comparable between the Nexavar and the placebo group with regard to ECOG status (status 0:
Demografske značilnosti in izhodiščne značilnosti bolezni so bile med skupino, ki se je zdravila z Nexavarjem in skupino, ki je dobivala placebo primerljive glede na stanje po ECOG (stanje 0:
54%; status 1:
54% v prim. s 54%; status 1:
39%; status 2:
38% v prim. z 39%; stanje 2:
7%), TNM stage (stage I: < 1% vs. < 1%; stage II:
8% v prim. s 7%), stadij TNM (stadij I: < 1% v prim. z < 1%; stadij II:
8.3%; stage III:
10, 4% v prim. z 8, 3%; stadij III:
43.6%; stage IV:
37, 8% v prim. s 43, 6%; stadij IV:
46.9%), and BCLC stage (stage B:
50, 8% v prim. s 46, 9%) in stadij BCLC (stadij B:
16.8%; stage C:
18, 1% v prim. s 16, 8%; stadij C:
83.2%; stage D: < 1% vs.
81, 6% v prim. s 83, 2%; stadij D: < 1% v prim.
The study was stopped after a planned interim analysis of OS had crossed the prespecified efficacy boundary.
Študija je bila ustavljena po načrtovani vmesni analizi celotnega preživetja, ker je bila presežena vnaprej določena meja učinkovitosti.
This OS analysis showed a statistically significant advantage for Nexavar over placebo for OS (HR:
Kar zadeva celotno preživetje, je analiza pokazala statistično značilno prednost Nexavarja pred placebom (razmerje ogroženosti:
0.69, p = 0.00058, see Table 4).
0, 69, p = 0, 00058, glejte preglednico 4).
In the prespecified stratification factors (ECOG status, presence or absence of macroscopic vascular invasion and/ or extrahepatic tumour spread) the hazard ratio consistently favoured Nexavar over placebo.
Pri vnaprej določenih stratifikacijskih faktorjih (stanje po ECOG, prisotnost ali odsotnost makroskopske žilne prizadetosti in/ ali širjenja tumorja zunaj jeter) je bilo razmerje ogroženosti dosledno v prid Nexavarju v primerjavi s placebom.
The descriptive subgroup analysis suggested a potentially less pronounced treatment effect for the subgroups of patients below 65 years of age and those with metastatic disease.
Opisna analiza podskupin je nakazala, da bi bil učinek zdravljenja morda lahko manj izraziti v podskupinah bolnikov, mlajših od 65 let, in bolnikov z metastatsko boleznijo.
There are limited data from this study in patients with Child Pugh B liver impairment and only one patient with Child Pugh C had been included.
Iz te študije je na voljo le malo podatkov o bolnikih z okvaro jeter stopnje B po Child Pughu, medtem ko je bil z okvaro stopnje C po Child Pughu vključen le en bolnik.
10 Table 4:
Preglednica 4:
Efficacy Results from study 3 (study 100554) in hepatocellular carcinoma
Rezultati učinkovitosti iz študije 3 (študija 100554) pri karcinomu jetrnih celic.
Nexavar (N=299)
Nexavar (n = 299)
Placebo (N=303)
Placebo (n = 303)
HR (95% CI)
RO (95% IZ)
Overall Survival (OS) [median, weeks (95% CI)]
Celotno preživetje [mediana, tedni (95% IZ)]
Time to Progression (TTP) [median, weeks (95% CI)]**
Čas do napredovanja [mediana, tedni (95% IZ)] **
CI=Confidence interval, HR=Hazard ratio (Nexavar over placebo) *statistically significant as the p-value was below the prespecified O’ Brien Fleming stopping boundary of 0.0077 **independent radiological review
IZ = interval zaupanja, RO = razmerje ogroženosti (Nexavar proti placebu) * statistično značilno, ker je bila vrednost p pod vnaprej določeno vrednostjo O’ Brien- Flemingove ustavitvene meje 0, 0077. ** neodvisen radiološki pregled
Renal cell carcinoma The safety and efficacy of Nexavar in the treatment of advanced renal cell carcinoma (RCC) were investigated in two clinical studies:
Karcinom ledvičnih celic Varnost in učinkovitost Nexavarja za zdravljenje napredovalega karcinoma ledvičnih celic so preučevali v dveh kliničnih študijah:
Study 1 (study 11213) was a Phase III, multi-centre, randomised, double blind, placebo-controlled study in 903 patients.
Študija 1 (študija 11213) je bila multicentrična, randomizirana, dvojno slepa, s placebom kontrolirana študija III. faze, v katero so bili vključeni 903 bolniki.
Only patients with clear cell renal carcinoma and low and intermediate risk MSKCC (Memorial Sloan Kettering Cancer Center) were included.
Vključeni so bili samo bolniki s svetloceličnim karcinomom ledvičnih celic in z majhnim ali zmernim tveganjem po MSKCC (Memorial Sloan Kettering Cancer Center).
The primary endpoints were overall survival and progression-free survival (PFS).
PFS (Progression- free Survival).
Approximately half of the patients had an ECOG performance status of 0, and half of the patients were in the low risk MSKCC prognostic group.
Približno polovica bolnikov je imela oceno stanja zmogljivosti ECOG 0 in polovica jih je bila po kriterijih MSKCC (Memorial Sloan Kettering Cancer Center) razvrščena v prognostično slabšo skupino.
PFS was evaluated by blinded independent radiological review using RECIST criteria.
11 PFS je bilo ovrednoteno z neodvisnim slepim kontrolnim pregledom radioloških posnetkov v skladu z merili RECIST.
The median PFS was 167 days for patients randomised to Nexavar compared to 84 days for placebo patients (HR = 0.44; 95% CI:
Srednja vrednost PFS je bila pri bolnikih, ki so se zdravili z Nexavarom 167 dni in pri tistih, ki so dobivali placebo 84 dni (HR = 0, 44; 95- odstotni interval zaupanja:
0.35 - 0.55; p < 0.000001).
0, 35 – 0, 55; p < 0, 000001).
Age, MSKCC prognostic group, ECOG PS and prior therapy did not affect the treatment effect size.
Starost, MSKCC prognostična skupina, ECOG PS in predhodno zdravljenje niso vplivali na obseg terapevtskega učinka.
The nominal alpha value for this analysis was 0.0094.
Nominalna alfa vrednost te analize je bila 0, 0094.
The median survival was 19.3 months for patients randomised to Nexavar compared to 15.9 months for placebo patients (HR = 0.77; 95% CI:
Srednja vrednost preživetja je bila 19, 3 mesecev pri bolnikih, ki so dobivali Nexavar in 15, 9 mesecev pri tistih, ki so dobivali placebo (HR = 00, 77; 95% CI:
At the time of this analysis, about 200 patients had crossed-over to sorafenib from the placebo group.
V tem času je približno 200 bolnikov iz skupine, ki je dobivala placebo prešlo na zdravljenje s sorafenibom.
Study 2 was a Phase II, discontinuation study in patients with metastatic malignancies, including RCC.
Študija 2 je bila izključitvena študija II. faze, v katero so bili vključeni bolniki z različnimi vrstami metastatskega raka, tudi s KLC.
Patients with stable disease on therapy with Nexavar were randomised to placebo or continued Nexavar therapy.
Bolniki, ki so imeli ob zdravljenju z Nexavarom stabilno bolezen so bili randomizirani v skupino, ki je dobivala placebo ali skupino, ki je nadaljevala zdravljenje z Nexavarom.
Progression-free survival in patients with RCC was significantly longer in the Nexavar group (163 days) than in the placebo group (41 days) (p = 0.0001, HR = 0.29).
Pri bolnikih s KCL, ki so jemali Nexavar, je bilo preživetje brez napredovanja bolezni (PFS) značilno daljše (163 dni), kot pri tistih, ki so prejemali placebo (41 dni) (p = 0, 0001, HR = 0, 29).
After administration of Nexavar tablets the mean relative bioavailability is 38 - 49% when compared to an oral solution.
Absorpcija in porazdelitev Srednja relativna biološka uporabnost tablet Nexavar je v primerjavi s peroralno raztopino 38 - do 49 - odstotna.
Following oral administration sorafenib reaches peak plasma concentrations in approximately 3 hours.
Po peroralni uporabi je plazemska koncentracija sorafeniba največja v približno treh urah.
When given with a high-fat meal sorafenib absorption was reduced by 30% compared to administration in the fasted state.
Če se ga zaužije z zelo mastno hrano, se njegova absorpcija v primerjavi s tisto po zaužitju na tešče zmanjša za 30%.
Mean Cmax and AUC increased less than proportionally beyond doses of 400 mg administered twice daily.
Pri odmerkih več kot 400 mg dvakrat na dan, se srednja Cmax in AUC nista zvečala sorazmerno z odmerki.
In vitro binding of sorafenib to human plasma proteins is 99.5%.
In vitro se na humane plazemske beljakovine veže 99, 5% sorafeniba.
Multiple dosing of Nexavar for 7 days resulted in a 2.5- to 7-fold accumulation compared to single dose administration.
Po sedem dnevnem večkratnem odmerjanju Nexavara se je pojavilo 2, 5 do 7- kratno kopičenje v primerjavi z enkratnim odmerkom.
Steady state plasma sorafenib concentrations are achieved within 7 days, with a peak to trough ratio of mean concentrations of less than 2.
Sorafenib doseže koncentracijo stanja dinamičnega ravnovesja v sedmih dneh s povprečnim razmerjem » peak to trough « manj kot 2.
The elimination half-life of sorafenib is approximately 25 - 48 hours.
Presnova in izločanje Razpolovna doba izločanja sorafeniba traja približno 25 do 48 ur.
Sorafenib is metabolised primarily in the liver and undergoes oxidative metabolism, mediated by CYP 3A4, as well as glucuronidation mediated by UGT1A9.
Sorafenib se presnovi predvsem v jetrih, in sicer z oksidacijsko presnovo, pri kateri posreduje CYP3A4, in glukuronizacijo, pri kateri posreduje UGT1A9.
Sorafenib accounts for approximately 70 - 85% of the circulating analytes in plasma at steady state.
V stanju dinamičnega ravnovesja kroži v plazmi približno 70 do 85% presnovkov sorafeniba.
The main circulating metabolite of sorafenib in plasma, the pyridine N-oxide, shows in vitro potency similar to that of sorafenib.
Moč glavnega krožečega presnovka sorafeniba v plazmi, piridin N- oksida, je in vitro podobna sorafenibovi.
This metabolite comprises approximately 9 - 16% of circulating analytes at steady state.
Ta presnovek predstavlja približno 9 do 16% presnovkov v stanju dinamičnega ravnovesja, ki krožijo.
Following oral administration of a 100 mg dose of a solution formulation of sorafenib, 96% of the dose was recovered within 14 days, with 77% of the dose excreted in faeces, and 19% of the dose excreted in urine as glucuronidated metabolites.
Po peroralnem zaužitju 100- miligramskega odmerka raztopine sorafeniba so po 14 dneh zbrali 96% odmerka, 77% se ga je izločilo z blatom, 19% pa s sečem v obliki glukuronidnih presnovkov.
Unchanged sorafenib, accounting for 51% of the dose, was found in faeces but not in urine, indicating that biliary excretion of unchanged drug might contribute to the elimination of sorafenib.
51% odmerka, so odkrili v blatu, ne pa tudi v seču, kar kaže na to, da se sorafenib izloča z žolčem.
Pharmacokinetics in special populations:
Farmakokinetika pri posebnih skupinah:
Analyses of demographic data suggest that there is no relationship between pharmacokinetics and age (up to 65 years) gender or body weight.
Analize demografskih podatkov kažejo, da ni povezave med farmakokinetiko in bolnikovo starostjo (do 65 let), spolom ali telesno maso.
Paediatric Population:
Otroci:
No studies have been conducted to investigate the pharmacokinetics of sorafenib in paediatric patients.
Študij o farmakokinetičnih lastnostih sorafeniba pri otrocih ni bilo.
Renal impairment:
12 Ledvična okvara:
In four Phase I clinical trials, steady state exposure to sorafenib was similar in patients with mild or moderate renal impairment compared to the exposures in patients with normal renal function.
V štirih kliničnih preskušanjih I. faze je bila uravnotežena izpostavljenost sorafenibu pri bolnikih z blago ali zmerno hudo ledvično okvaro podobna kot pri bolnikih z normalnim delovanjem ledvic.
In a clinical pharmacology study (single dose of 400 mg sorafenib), no relationship was observed between sorafenib exposure and renal function in subjects with normal renal function, mild, moderate or severe renal impairment.
V študiji klinične farmakologije (posamezen odmerek 400 mg sorafeniba) niso povezanosti med izpostavljenostjo sorafenibu in delovanjem ledvic opazili niti pri bolnikih z normalnim delovanjem ledvic niti pri tistih z blago, zmerno ali hudo ledvično okvaro.
No data is available in patients requiring dialysis.
Za bolnike, ki potrebujejo dializo, ni podatkov.
In hepatocellular carcinoma patients with mild or moderate hepatic impairment, exposure values were comparable and within the range of exposures observed in patients without hepatic impairment.
Pri bolnikih s hepatocelularnim karcinomom z blago ali zmerno hudo jetrno okvaro so bile vrednosti izpostavljenosti primerljive in v okviru tistih, ki so jih ugotovili pri bolnikih brez jetrne okvare.
There are no data for patients with Child-Pugh C (severe) hepatic impairment.
Podatkov o bolnikih s hudo jetrno okvaro (Child- Pugh C) ni.
Sorafenib is mainly eliminated via the liver, and exposure might be increased in this patient population.
Sorafenib se izloča v glavnem skozi jetra, zaradi česar se izpostavljenost teh bolnikov sorafenibu lahko zveča.
The preclinical safety profile of sorafenib was assessed in mice, rats, dogs and rabbits.
Predklinično varnost sorafeniba so ocenjevali pri miših, podganah, psih in kuncih.
Repeat-dose toxicity studies revealed changes (degenerations and regenerations) in various organs at exposures below the anticipated clinical exposure (based on AUC comparisons).
V študijah o toksičnosti pri ponavljajočih se odmerkih so odkrili spremembe (degeneracije in regeneracije) različnih organov, kadar je bila izpostavljenost manjša od pričakovane klinične (temelji na primerjavi AUC).
After repeated dosing to young and growing dogs effects on bone and teeth were observed at exposures below the clinical exposure.
Po ponavljajočem se odmerjanju sorafeniba mladim psom v razvoju so opazili vpliv na kosti in zobe, kadar je bila izpostavljenost manjša od klinične.
Changes consisted in irregular thickening of the femoral growth plate, hypocellularity of the bone marrow next to the altered growth plate and alterations of the dentin composition.
Spremembe so bile povezane z nepravilno rastjo stegenskega rastnega hrustanca, hipocelularnostjo kostnega mozga pri spremenjenem rastnem hrustancu in s spremembami strukture zobnega dentina.
The standard program of genotoxicity studies was conducted and positive results were obtained as an increase in structural chromosomal aberrations in an in vitro mammalian cell assay (Chinese hamster ovary) for clastogenicity in the presence of metabolic activation was seen.
Rezultat je bil v poskusu in vitro na celicah sesalcev (jajčniki samic kitajskega hrčka) pozitiven v smislu zvečanega števila strukturnih kromosomskih aberacij, v navzočnosti presnovne aktivacije je bila ugotovljena klastogenost.
One intermediate in the manufacturing process, which is also present in the final drug substance (< 0.15%), was positive for mutagenesis in an in vitro bacterial cell assay (Ames test).
V in vitro bakterijskem testu (Amesov test) je bil eden od vmesnih produktov sinteze sorafeniba, ki se nahaja tudi v končni učinkovini (< 0, 15%) pozitiven na mutagenezo.
Furthermore, the sorafenib batch tested in the standard genotoxicity battery included 0.34% PAPE.
Poleg tega je v skupini standardnega genotoksičnega testiranja sorafeniba vključeval 0, 34% PAPE.
Carcinogenicity studies have not been conducted with sorafenib.
Študij o karcinogenem delovanju sorafeniba ni bilo.
12 No specific studies with sorafenib have been conducted in animals to evaluate the effect on fertility.
Posebnih študij za oceno vpliva na razmnoževanje pri živalih ni bilo.