natgillin/translations-raw huggingface dataset:
In a retrospective responder analysis based on change in walking distance, WHO functional class and dyspnoea of the 95 patients randomised to Tracleer 125 mg twice daily in the placebo-controlled trials, it was found that at week 8, 66 patients had improved, 22 were stable and 7 had deteriorated.
Za bolnike, ki so se odzvali na zdravljenje, je kasnejša retrospektivna analiza na podlagi spremembe prehojene razdalje, funkcijskega razreda po klasifikaciji Svetovne zdravstvene organizacije in dispneje pri 95 bolnikih, ki so v randomiziranih s placebom nadzorovanih preskušanjih jemali zdravilo Tracleer v odmerku 125 mg dvakrat na dan, pokazala, da je po 8 tednih pri 66 bolnikih prišlo do izboljšanja stanja, pri 22 bolnikih je bilo stanje stabilno, pri 7 bolnikih pa je prišlo do poslabšanja.
Of the 22 patients stable at week 8, 6 improved at week 12/16 and 4 deteriorated compared with baseline.
Od 22 v 8. tednu stabilnih bolnikov se je pri 6 bolnikih stanje izboljšalo v 12. / 16. tednu, pri 4 bolnikih pa se je stanje v primerjavi z izhodiščnim stanjem poslabšalo.
Of the 7 patients that deteriorated at week 8, 3 improved at week 12/16 and 4 deteriorated compared with baseline.
Od 7 bolnikov s poslabšanjem stanja v 8. tednu, se je pri 3 bolnikih stanje izboljšalo v 12. / 16. tednu, pri 4 bolnikih pa se je stanje v primerjavi z izhodiščnim stanjem poslabšalo.
Treatment with Tracleer led to a significant increase in cardiac index associated with a significant reduction in pulmonary artery pressure, pulmonary vascular resistance and mean right atrial pressure.
Zdravljenje z zdravilom Tracleer je povzročilo značilno povečanje srčnega indeksa, povezanega s pomembnim znižanjem pljučnega arterijskega tlaka, pljučnega žilnega upora in srednjega tlaka v desnem preddvoru.
A reduction in symptoms of pulmonary arterial hypertension was observed with Tracleer treatment.
Pri zdravljenju z zdravilom Tracleer so poročali o manj pogostih simptomih pljučne arterijske hipertenzije.
Dyspnoea measurement during walk tests showed an improvement in Tracleer-treated patients.
Meritve dispneje med preskusi s hojo so pokazale izboljšanje pri bolnikih, ki so jemali zdravilo Tracleer.
In the AC-052-352 trial, 92% of the 213 patients were classified at baseline as WHO functional class III and 8% as class IV.
V preskušanju AC- 052- 352 so 92% od 213 bolnikov izhodiščno opredelili v funkcijski razred III po klasifikaciji Svetovne zdravstvene organizacije, 8% pa v razred IV.
Treatment with Tracleer led to a WHO functional class improvement in 42.4% of patients (placebo 30.4%).
Zdravljenje z zdravilom Tracleer je pri 42, 4% bolnikov povzročilo izboljšanje funkcijskega razreda po klasifikaciji Svetovne zdravstvene organizacije (placebo 30, 4%).
The overall change in WHO functional class during both trials was significantly better among Tracleer-treated patients as compared with placebo-treated patients.
Skupna sprememba funkcijskega razreda po klasifikaciji Svetovne zdravstvene organizacije v obeh preskušanjih je bila značilno boljša med bolniki, ki so jemali zdravilo Tracleer, kot pri bolnikih, ki so prejemali placebo.
Treatment with Tracleer was associated with a significant reduction in the rate of clinical worsening compared with placebo at 28 weeks (10.7% vs 37.1%, respectively; p = 0.0015).
Zdravljenje z zdravilom Tracleer so v 28. tednu povezovali z značilnim zmanjšanjem stopnje kliničnega poslabšanja v primerjavi s placebom (10, 7% pri zdravilu Tracleer proti 37, 1% pri placebu, p = 0, 0015).
In a randomised, double-blind, multi-centre, placebo-controlled trial (AC-052-364; EARLY),185 PAH patie nts in WHO functional class II (mean baseline 6-minute walk distance of 435 metres) received bosentan 62.5 mg b.i.d. for 4 weeks followed by 125 mg b.i.d.
V randomiziranem, dvojno slepem, multicentričnem, s placebom nadziranem preskušanju (AC- 052- 364; EARLY) je 185 bolnikov s PAH II. funkcijskega razreda po SZO (srednja izhodiščna vrednost 435 metrov prehojenih v 6 minutah) prejemalo bosentan 62, 5 mg dvakrat na dan 4 tedne in nato 125 mg dvakrat na teden (n = 93), ali placebo (n = 92) 6 mesecev.
The co-primary endpoints were percentage change from baseline in PVR and change from baseline in 6-minute walk distance to Month 6 versus placebo.
Dodatne primarne končne točke so bile spremembe od izhodiščne vrednosti od izhodišča pri pljučno- žilnem uporu (PŽU) in sprememba prehojene razdalje v 6 minutah hoje od izhodiščne vrednosti do 6. meseca proti placebu.
The table below illustrates the pre- specified protocol analyses.
Spodnja tabela kaže predspecificirane analize protokola.
PVR (dyn.sec/cm5)
PŽU (din. s/ cm5)
802 (365) 128 (465)
Bosentan (n = 86)
95% CL
95% Cl
Treatment with bosentan was associated with a reduction in the rate of clinical worsening, defined as a composite of symptomatic progression, hospitalisation for PAH and death, compared with placebo (proportional risk reduction 77%, 95% CI 20%–94%, p = 0.0114).
Zdravljenje z bosentanom so povezali z zmanjšanjem stopnje kliničnega poslabšanja, opredeljeno kot sklop simptomatičnega napredovanja, hospitalizacije zaradi PAH in smrti v primerjavi s placebom (sorazmerno zmanjšanje tveganja 77%, 95% CI 20% – 94%, p = 0, 0114).
There was one hospitalisation related to PAH worsening in the bosentan group and 3 hospitalisations in the placebo group.
V zvezi s poslabšanjem PAH je bila hospitalizirana ena oseba iz skupine z bosentanom in 3 osebe iz skupine s placebom.
Only one death occurred in each treatment group during the 6-month double-blind study period, therefore no conclusion can be drawn on survival.
V vsaki skupini je v času 6- mesečnega obdobja dvojno slepe študije umrla po ena oseba, zato o preživetju ni mogoče sklepati.
In a prospective, multi-centre, randomized, double-blind, placebo-controlled study (BREATHE-5), patients with pulmonary arterial hypertension WHO functional Class III and Eisenmenger physiology associated with congenital heart disease received Tracleer 62.5 mg bid for 4 weeks, then 125 mg b.i.d. for a further 12 weeks (n = 37), or placebo (n = 17).
14 V prospektivni multicentrični randomizirani dvojno slepi s placebom nadzorovani študiji (BREATHE- 5) so bolniki s PAH razreda III po klasifikaciji WHO in Eisenmengerjevo fiziologijo, povezanim s kongenitalno srčno boleznijo, 4 tedne prejemali zdravilo Tracleer 62, 5 mg dvakrat na dan, nato pa nadaljnjih 12 tednov 125 mg dvakrat na dan (n = 37) ali placebo (n = 17).
The primary objective was to show that Tracleer did not worsen hypoxaemia.
Primarni cilj je bil pokazati, da zdravilo Tracleer ni poslabšalo hipoksemije.
After 16 weeks, the mean oxygen saturation was increased in the bosentan group by 1.0% (95% CI –0.7; 2.8%) as compared to the placebo group, showing that
Po 16 tednih je bila v skupini, ki je prejemala bosentan, povprečna saturacija s kisikom za 1, 0% (95% IZ– 0, 7; 2, 8%) večja kot pri skupini, ki je prejemala placebo, kar je dokazalo, da bosentan ni poslabšal hipoksemije.
After 16 weeks, the mean placebo-corrected increase in 6-minute walk distance was 53 meters (p = 0.0079) reflecting improvement of exercise capacity.
Po 16 tednih je bilo povprečje s placebom korigiranega podaljšanja razdalje, prehojene v 6 minutah, 53 metrov (p = 0, 0079), kar je kazalo izboljšanje zmogljivosti bolnikov za telesno vadbo.
An open label, non-comparative study (AC-052-362; BREATHE-4) was performed in 16 patients with WHO Class III PAH associated with HIV infection.
V odprti, neprimerjalni študiji (AC- 052- 362; BREATHE- 4) je sodelovalo šestnajst bolnikov s PAH (razreda III po klasifikaciji WHO), povezanim z okužbo HIV.
Patients were treated with Tracleer 62.5 mg bid for 4 weeks followed by 125 mg bid for a further 12 weeks.
Štiri tedne so prejemali zdravilo Tracleer 62, 5 mg dvakrat na dan, nato pa nadaljnjih 12 tednov 125 mg dvakrat na dan.
After 16 weeks treatment, there were significant improvements from baseline in exercise capacity: mean increase in 6-minute walk test: +91.4 meters from 332.6 meters on average at baseline (p < 0.001).
91, 4 metra s povprečne izhodiščne razdalje 332, 6 metra (p < 0, 001).
As part of the safety assessment, the effect of bosentan on the antiretroviral therapy (i.e. reduced systemic concentrations of the co- administered antiretroviral agents with a potential negative impact on the efficacy of the antiretroviral therapy) was assessed through CD4 cell counts and HIV-1 RNA titers.
Pri oceni varnosti so učinek bosentana na protiretrovirusno zdravljenje (tj. zmanjšane sistemske koncentracije sočasno uporabljenega antiretrovirusnega zdravila z morebitnimi negativnimi vplivi na učinek protiretrovirusnega zdravljenja) ocenili s spremljanjem koncentracije celic CD4 in titrov RNA HIV- 1.
Given the limitations of the study (small number of patients, non-standardized pharmacokinetic investigation of antiretroviral drugs, heterogeneity of drug regimens), no formal conclusion can be drawn regarding the effects of bosentan on antiretroviral drug efficacy.
Glede na omejitve študije (majhno število bolnikov, nestandardizirane farmakokinetične preiskave protiretrovirusnih zdravil, heterogenost režima zdravljenja) ni bilo mogoče sklepati o učinkih bosentana na učinkovitost protiretrovirusnih zdravil.
An increase in HIV viral load was observed in 5 patients (see also Section 4.4).
Pri 5 bolnikih so opazili povečanje koncentracije virusa HIV (glejte tudi poglavje 4. 4).
No clinical data are available after 16 weeks from this study.
16 tednov po tej študiji ni na voljo nobenih kliničnih podatkov.
There are no studies to demonstrate beneficial effects on survival of treatment with Tracleer.
Raziskav, s katerimi bi pokazali koristne učinke zdravljenja z zdravilom Tracleer na preživetje bolnikov, ni.
However, long-term vital status was recorded for all 235 patients who were treated with bosentan in the two pivotal placebo-controlled trials (AC-052-351 and AC-052-352) and/or their two uncontrolled, open- label extensions.
Vendar so v dveh ključnih s placebom nadzorovanih preskušanjih (AC- 052- 351 in AC- 052- 352) in/ ali njunih dveh nekontroliranih podaljšanjih z znanim zdravilom pri vseh 235 bolnikih, ki so jih zdravili z bosentanom, dolgoročno spremljali vitalno stanje.
3.3 years] and patients were observed for a mean of 2.0 ± 0.6 years.
Povprečno trajanje izpostavljenosti bosentanu je bilo 1, 9 let ± 0, 7 let [najmanj 0, 1 let, največ 3, 3 let], bolnike pa so opazovali povprečno 2, 0 ± 0, 6 let.
The majority of patients were diagnosed as PPH (72%) and were in WHO functional class III (84%).
Pri večini bolnikov so ugotovili PPH (72%), bili pa so v III. funkcijskem razredu po merilih SZO (84%).
In this total population, Kaplan-Meier estimates of survival were 93% and 84% after 1 and 2 years after the start of treatment with Tracleer, respectively.
V tej skupni populaciji je bila po 1 letu zdravljenja z zdravilom Tracleer ocena preživetja po metodi Kaplan- Meier 93 - odstotna, po 2 letih zdravljenja pa 84- odstotna.
The estimates may have been influenced by the initiation of epoprostenol treatment in 43/235 patients.
Pri 43/ 235 bolnikih je na oceno morda vplivalo zdravljenje z epoprostenolom.
Study performed in children with pulmonary arterial hypertension One study has been conducted in children with pulmonary hypertension.
Študije pri otrocih s pljučno arterijsko hipertenzijo Pri otrocih s pljučno hipertenzijo so opravili eno študijo.
Tracleer has been evaluated in an open-label non-controlled study in 19 paediatric patients with pulmonary arterial hypertension (AC-052-356, BREATHE-3: primary pulmonary hypertension 10 patients, and pulmonary arterial hypertension related to congenital heart diseases 9 patients).
10 bolnikov s primarno pljučno hipertenzijo in 9 bolnikov s pljučno arterijsko hipertenzijo, povezano s prirojenimi boleznimi srca).
This study was primarily designed as a pharmacokinetic study (see section 5.2).
Ta študija je bila zasnovana predvsem kot farmakokinetična študija (glejte poglavje 5. 2).
Patients were divided into and dosed according to three body- weight groups (see section 4.2) for 12 weeks.
Bolnike so razvrstili v tri skupine glede na telesno maso (glejte poglavje 4. 2) in jim glede na razvrstitev določili odmerek, ki so ga prejemali 12 tednov.
Half of the patients in each group were already being treated with intravenous epoprostenol and the dose of epoprostenol remained constant for the duration of the trial.
Polovica bolnikov v vsaki skupini je že prejemala epoprostenol intravensko, odmerek epoprostenola je med trajanjem preskušanja ostal nespremenjen.
The age range was 3–15 years.
Bolniki so bili stari od 3 do 15 let.
Patients were in WHO functional class II (N = 15 patients, 79%) or class III (N = 4 patients, 21%) at baseline.
Bolniki so bili izhodiščno po klasifikaciji Svetovne zdravstvene organizacije v funkcijskem razredu II (n = 15 bolnikov, 79%) ali razredu III (n = 4 bolniki, 21%).
The mean increase from baseline in cardiac index was 0.5 l/min/m2, the mean decrease in mean pulmonary arterial pressure was 8 mmHg, and the mean decrease in pulmonary vascular resistance was 389 dyn·sec·cm-5.
Povprečno povečanje srčnega indeksa od izhodiščne vrednosti je bilo 0, 5 l/ min/ m2, povprečno znižanje povprečnega pljučnega arterijskega tlaka je bilo 8 mm Hg in povprečno zmanjšanje pljučnega žilnega upora 389 din· s· cm- 5.
Combination with epoprostenol The combination of Tracleer and epoprostenol has been investigated in two studies:
15 Kombinacija z epoprostenolom Kombinacijo zdravila Tracleer in epoprostenola so raziskovali v dveh študijah:
AC-052-355 (BREATHE-2) and AC-052-356 (BREATHE-3).
AC- 052- 355 (BREATHE- 2) in AC- 052- 356 (BREATHE- 3).
AC-052-355 was a multi-centre, randomised, double-blind, parallel-group trial of Tracleer versus placebo in 33 patients with severe pulmonary arterial hypertension who were receiving concomitant epoprostenol therapy.
AC- 052- 355 je bila randomizirana multicentrična dvojno slepa študija, v kateri so s pomočjo vzporedne skupine primerjali zdravilo Tracleer s placebom pri 33 bolnikih s hudo pljučno arterijsko hipertenzijo, ki so sočasno prejemali epoprostenol.
AC-052-356 was an open-label, non-controlled trial; 10 of the 19 paediatric patients were on concomitant Tracleer and epoprostenol therapy during the 12-week trial.
AC- 052- 356 je bilo nenandzorovano preskušanje z znanim zdravilom; 10 od 19 pediatričnih bolnikov je v času 12- tedenskega preskušanja sočasno jemalo zdravilo Tracleer in epoprostenol.
15 Systemic sclerosis with digital ulcer disease Two randomised, double-blind, multi-centre, placebo-controlled trials have been conducted in 122 (Study AC-052-401, RAPIDS-1) and 190 (Study AC-052-331, RAPIDS-2) adult patients with systemic sclerosis and digital ulcer disease (either ongoing digital ulcers or a history of digital ulcers within the last year).
Sistemska skleroza z boleznijo razjed prstov Opravili so dve randomizirani dvojno slepi multicentrični s placebom nadzorovani študiji in sicer pri 122 (študija AC- 052- 401, RAPIDS- 1) in 190 (študija AC- 052- 331, RAPIDS- 2) odraslih bolnikih s sistemsko sklerozo in boleznijo razjed prstov (bodisi dolgotrajnimi razjedami prstov ali z anamnezo razjed prstov v zadnjem letu).
In study AC-052-331, patients had to have at least one digital ulcer of recent onset, and across the two studies 85% of patients had ongoing digital ulcer disease at baseline.
V študiji AC- 052- 331 so bolniki morali imeti vsaj eno razjedo na prstih, ki je nastopila nedavno in v obeh študijah je 85% bolnikov imelo dolgotrajno bolezen razjed prstov.
After 4 weeks of Tracleer 62.5 mg twice daily, the maintenance doses studied in both these trials were 125 mg twice daily.
Po 4 tednih jemanja zdravila Tracleer v odmerku 62, 5 mg dvakrat na dan so bili vzdrževalni odmerki, preučevani v teh preskušanjih, 125 mg dvakrat na dan.
The duration of double-blind therapy was 16 weeks in study AC-052-401, and 24 weeks in study AC-052-331.
Dvojno slepa terapija je v študiji AC- 052- 401 trajala 16 tednov in v študiji AC- 052- 331 24 tednov.
The number of new digital ulcers from baseline to study endpoint was a primary endpoint in both studies.
Primarna končna točka obeh študij je bila število novih razjed prstov od osnove do končne točke študije.
Treatment with Tracleer resulted in fewer new digital ulcers for the duration of therapy, compared with placebo.
Zdravljenje z zdravilom Tracleer je v primerjavi s placebom pripeljalo do manj novih razjed prstov med trajanjem terapije.
2.7 new digital ulcers in the placebo group (p = 0.0042).
V študiji AC- 052- 401 so bolniki v skupini, zdravljeni z bosetanom, med 16- tedensko dvojno slepo terapijo razvili povprečno 1, 4 nove razjede na prstih nasproti 2, 7 novim razjedam v skupini, zdravljeni s placebom (p = 0, 0042).
2.7 new digital ulcers, respectively (p = 0.0351).
V študiji AC- 052- 331 so bile ustrezne številke med 24- tedensko dvojno slepo terapijo 1, 9 proti 2, 7 novih razjed prstov v enakem zaporedju (p = 0, 0351).
Limited data in patients show that the exposure to bosentan in adult pulmonary arterial hypertension patients is approximately 2-fold greater than in healthy adult subjects.
Omejeni podatki, ki so na voljo za bolnike, kažejo, da je izpostavljenost bosentanu pri odraslih bolnikih s pljučno arterijsko hipertenzijo približno 2- krat večja kot pri zdravih odraslih.
At higher oral doses Cmax and AUC increase less than proportionally to the dose.
Pri višjih peroralnih odmerkih se Cmax in AUC povečujeta manj kot bi bilo sorazmerno odmerku.
In healthy subjects the absolute bioavailability of bosentan is approximately 50% and is not affected by food.
Pri zdravih osebah je absolutna biološka uporabnost bosentana približno 50% in ni odvisna od hrane.
The maximum plasma concentrations are attained within 3–5 hours.
Maksimalne plazemske koncentracije dosega v 3– 5 urah.
Bosentan is highly bound (> 98%) to plasma proteins, mainly albumin.
Bosentan se v veliki meri veže (> 98%) na plazemske beljakovine, zlasti na albumine.
16 Upon multiple dosing, plasma concentrations of bosentan decrease gradually to 50%–65% of those seen after single dose administration.
16 Biotransformacija in eliminacija
Steady-state conditions are reached within 3–5 days.
Stanje dinamičnega ravnovesja se vzpostavi v 3– 5 dneh.
Less than 3% of an administered oral dose is recovered in urine.
Manj kot 3% danega peroralnega odmerka se izloči v urinu.
Bosentan is an inducer of CYP2C9 and CYP3A4 and possibly also of CYP2C19 and the P-glycoprotein.
Bosentan je induktor izoencimov CYP2C9 in CYP3A4 ter morebiti tudi CYP2C19 in P- glikoproteina.
No kinetic data are available in children under 3 years.
Za otroke, mlajše od 3 let, farmakokinetičnih podatkov ni.
Children The pharmacokinetics of single and multiple oral doses were studied in paediatric patients with pulmonary arterial hypertension who were dosed on the basis of body weight (see sections 4.2 and 5.1).
Otroci Farmakokinetiko enkratnega in večkratnih peroralnih odmerkov so preučevali pri pediatričnih bolnikih s pljučno arterijsko hipertenzijo, katerih odmerki so določili na podlagi telesne mase (glejte poglavji 4. 2 in 5. 1).
The exposure to bosentan decreased with time in a manner consistent with the known auto- induction properties of bosentan.
Izpostavljenost bosentanu se je manjšala s časom na način, ki se je ujemal z znanimi samoindukcijskimi lastnostmi bosentana.
The mean AUC (CV%) values of bosentan in paediatric patients treated with 31.25, 62.5 or 125 mg b.i.d. were 3496 (49), 5428 (79), and 6124 (27) ng·h/ml, respectively, and were lower than the value of 8149 (47) ng·h/ml observed in adult patients with pulmonary arterial hypertension receiving 125 mg b.i.d.
Srednja vrednost AUC (CV%) bosentana pri pediatričnih bolnikih, ki so prejemali 31, 25 mg bosentana dvakrat na dan, je bila 3496 (49) ng· h/ ml, pri 62, 5 mg dvakrat na dan 5428 (79) ng· h/ ml ter pri 125 mg dvakrat na dan 6124 (27) ng· h/ ml, in so bile nižje kot vrednost 8149 (47) ng· h/ ml, izmerjena pri odraslih bolnikih s pljučno arterijsko hipertenzijo, ki so jemali 125 mg dvakrat na dan.
At steady state the systemic exposure in paediatric patients weighing 10–20 kg, 20–40 kg and > 40kg were 43%, 67% and 75%, respectively, of the adult systemic exposure.
Sistemska izpostavljenost pri pediatričnih bolnikih, ki so tehtali 10– 20 kg, 20– 40 kg in > 40 kg, je bila v stanju dinamičnega ravnovesja 43%, 67% oziroma 75% sistemske izpostavljenosti pri odraslih.
The reason for this difference is unclear and possibly related to an increased hepatic metabolism and excretion.
Razlog za to razliko ni jasen, morda je povezan z okrepljeno presnovo v jetrih in povečanim izločanjem.
The consequences of these findings regarding hepatotoxicity are unknown.
Posledice teh najdb glede toksičnosti za jetra niso znane.
Gender and the concomitant use of intravenous epoprostenol had no significant effect on the pharmacokinetics of bosentan.
Spol in sočasna uporaba intravenskega epoprostenola nista pomembno vplivala na farmakokinetiko bosentana.
Hepatic impairment In patients with mildly impaired liver function (Child-Pugh class A) no relevant changes in the pharmacokinetics have been observed.
Okvarjeno delovanje jeter Pri bolnikih z blago okvarjenim delovanjem jeter (Child- Pugh razred A) niso opazili kakih pomembnih sprememb v farmakokinetiki.
The steady state AUC of bosentan was 9% higher and the AUC of the active metabolite, Ro 48-5033, was 33% higher in patients with mild hepatic impairment than in healthy volunteers.
V stanju dinamičnega ravnovesja je bila vrednost AUC bosentana za 9% večja in vrednost AUC za aktivni presnovek, Ro 48- 5033, za 33% večja pri bolnikih z blago okvarjenim delovanjem jeter kot pri zdravih prostovoljcih.
The pharmacokinetics of bosentan have not been studied in patients with Child- Pugh class B or C hepatic impairment and Tracleer is contra-indicated in this patient population (see section 4.3).
Farmakokinetike bosentana pri bolnikih z okvarjenim delovanjem jeter razreda B in C po klasifikaciji Child- Pugh niso raziskali, zato je zdravilo Tracleer pri tej skupini bolnikov kontraindicirano (glejte poglavje 4. 3).
Renal impairment In patients with severe renal impairment (creatinine clearance 15–30 ml/min), plasma concentrations of bosentan decreased by approximately 10%.
Okvarjeno delovanje ledvic Pri bolnikih s hudo okvarjenim delovanjem ledvic (očistek kreatinina 15– 30 ml/ min) so se plazemske koncentracije bosentana znižale za približno 10%.
No dose adjustment is required in patients with renal impairment.
Pri teh bolnikih so se plazemske koncentracije
17 5.3 Preclinical safety data
17 presnovkov bosentana povišale za približno 2- krat v primerjavi z osebami z normalnim ledvičnim delovanjem.
A 2-year carcinogenicity study in mice showed an increased combined incidence of hepatocellular adenomas and carcinomas in males, but not in females, at plasma concentrations about 2 to 4 times the plasma concentrations achieved at the therapeutic dose in humans.
Dvoletna študija kancerogenosti pri miših je pokazala povečanje incidence hepatocelularnih adenomov in karcinomov pri samcih, ne pa pri samicah, pri plazemskih koncentracijah, približno 2 - do 4- krat višjih od plazemskih koncentracij, doseženih pri ljudeh po terapevtskih odmerkih.
In rats, oral administration of bosentan for 2 years produced a small, significant increase in the combined incidence of thyroid follicular cell adenomas and carcinomas in males, but not in females, at plasma concentrations about 9 to 14 times the plasma concentrations achieved at the therapeutic dose in humans.
Pri podganah je peroralno dajanje bosentana preko obdobja dveh let povzročilo majhno, a pomembno povečanje incidence adenomov in karcinomov ščitničnih folikularnih celic pri samcih, ne pa pri samicah, pri plazemskih koncentracijah, približno 9 - do 14- krat višjih od plazemskih koncentracij, doseženih pri ljudeh po terapevtskih odmerkih.
There was evidence for a mild thyroid hormonal imbalance induced by bosentan in rats.
Pri podganah so dokazali, da bosentan povzroča blago hormonsko neravnovesje v ščitnici.