natgillin/translations-raw huggingface dataset:
DEX 10 mg/ m2 oral, days 1-5; VCR 2 mg i. v., days 6, 13, 20; daunorubicin 45 mg/ m2 i. v., days 6-7, 13-14
3. - 5. dan; MTX 15 mg intratekalno, 1. dan; metilprednizolon 40 mg intratekalno, 1. dan DEX 10 mg/ m2 peroralno, 1. - 5. dan; CP 200 mg/ m2 i. v., 3. - 5. dan; MTX 15 mg intratekalno, 1. dan DEX 10 mg/ m2 peroralno, 1. - 5. dan; VCR 2 mg i. v., 6., 13., 20. dan; daunorubicin 45 mg/ m2 i. v., 6. - 7., 13. - 14. dan CP 1 g/ m2 i. v.
(1 h), days 26, 46; Ara-C 75 mg/ m2 i. v.
(1 ura), 26., 46. dan; Ara- C 75 mg/ m2 i. v.
(1 h), days 28-31, 35-38, 42-45; 6-MP 60 mg/ m2 oral, days 26-46
(1 ura), 28. - 31., 35. - 38., 42. - 45. dan; 6- MP 60 mg/ m2 peroralno, 26. - 46. dan DEX 10 mg/ m2 peroralno, 1. - 5. dan; vindezin 3 mg/ m2 i. v., 1. dan; MTX
Consolidation therapy Study AJP01
zdravljenje Študija AJP01 indukcijsko zdravljenje konsolidacijsko zdravljenje vzdrževanje Študija AUS01
DEX 10 mg/ m2 oral, days 1-5; vindesine 3 mg/ m2 i. v., day 1; MTX 1.5 g/ m2 i. v.
19 1, 5 g/ m2 i. v.
(24 h), day 1; etoposide 250 mg/ m2 i. v.
(24 ur), 1. dan; etopozid 250 mg/ m2 i. v.
(1 h) days 4-5; Ara- C 2x 2 g/ m2 i. v.
(1 ura) 4. - 5. dan; Ara- C 2x 2 g/ m2 i. v.
CP 1.2 g/ m2 i. v.
(3 ure, na 12 ur), 5. dan CP 1, 2 g/ m2 i. v.
(3 h), day 1; daunorubicin 60 mg/ m2 i. v.
(3 ure), 1. dan; daunorubicin 60 mg/ m2 i. v.
(1 h), days 1-3; vincristine 1.3 mg/ m2 i. v., days 1, 8, 15, 21; prednisolone 60 mg/ m2/ day oral
(1 ura), 1. - 3. dan; vinkristin 1, 3 mg/ m2 i. v., 1., 8., 15., 21. dan; prednizolon 60 mg/ m2/ dan peroralno izmenična kemoterapija: visokoodmerna kemoterapija z MTX 1 g/ m2 i. v.
(24 h), day 1, and Ara-C 2 g/ m2 i. v.
(24 ur), 1. dan in Ara- C 2 g/ m2 i. v.
VCR 1.3 g/ m2 i. v., day 1; prednisolone 60 mg/ m2 oral, days 1-5
(na 12 ur), 2. - 3. dan, v 4 ciklusih VCR 1, 3 g/ m2 i. v., 1. dan; prednizolon 60 mg/ m2 peroralno, 1. - 5. dan
Hyper-CVAD regimen:
hyper- CVAD shema:
(3 h, q 12 h), days 1-3; vincristine 2 mg i. v., days 4, 11; doxorubicine 50 mg/ m2 i. v.
(3 ure, na 12 ur), 1. - 3. dan; indukcijsko - vinkristin 2 mg i. v., 4., 11. dan; doksorubicin 50 mg/ m2 i. v.
(24 h), day 1, Ara-C 1 g/ m2 i. v.
(24 ur), konsolidacijsko 4. dan; DEX 40 mg/ dan 1. - 4. in 11. - 14. dan, izmenjaje z MTX 1 g/ m2 i. v. zdravljenje (24 ur), 1. dan, Ara- C 1 g/ m2 i. v.
(2 h, q 12 h), days 2-3 (total of 8 courses)
(2 uri, na 12 ur), 2. - 3. dan (skupno 8 kur)
VCR 2 mg i. v. monthly for 13 months; prednisolone 200 mg oral, 5 days per month for 13 months
VCR 2 mg i. v. mesečno v obdobju 13 mesecev; prednizolon 200 mg peroralno, 5 dni na mesec v obdobju 13 mesecev
Ara-C: cytosine arabinoside; CP: cyclophosphamide; DEX: dexamethasone; MTX: methotrexate; 6-MP:
Ara- C: citozin arabinozid; CP: ciklofosfamid; DEX: deksametazon; MTX: metotreksat; 6- MP:
Teniposide; VCR: vincristine; IDA: idarubicine; i. v.: intravenous
6 - merkaptopurin; VM26: tenipozid; VCR: vinkristin; IDA: idarubicin; i. v.: intravensko
Relapsed/ refractory Ph+ ALL:
Relaps/ neodzivna Ph+ ALL:
When imatinib was used as single agent in patients with relapsed/ refractory Ph+ ALL, it resulted, in the 53 out of 411 patients evaluable for response, in a haematological response rate of 30% (9% complete) and a major cytogenetic response rate of 23%.
Zdravljenje z imatinibom kot edinim zdravilom pri bolnikih z relapsom/ neodzivno Ph+ ALL je povzročilo pri 53 od 411 za oceno odziva primernih bolnikov stopnjo hematološkega odziva 30% (v 9% popolni hematološki odziv) in stopnjo pomembnega citogenetičnega odziva 23%.
(Of note, out of the 411 patients, 353 were treated in an expanded access program without primary response data collected.) The median time to progression in the overall population of 411 patients with relapsed/ refractory Ph+ ALL ranged from 2.6 to 3.1 months, and median overall survival in the 401 evaluable patients ranged from 4.9 to 9 months.
(V pojasnilo: od 411 bolnikov jih je bilo 353 zdravljenih v programu razširjenega dostopa brez zbranih podatkov o primarnem odzivu.) Mediani čas do napredovanja bolezni je bil pri vseh 411 bolnikih z relapsom/ neodzivno Ph+ ALL v obsegu od 2, 6 do 3, 1 meseca, mediano preživetje nasploh pa je bilo pri 401 za oceno primernih bolnikov v obsegu od 4, 9 do 9 mesecev.
Clinical studies in MDS/ MPD Experience with Glivec in this indication is very limited and is based on haematological and cytogenetic response rates.
Klinične študije pri MDS/ MPD Za to indikacijo so izkušnje z zdravilom Glivec zelo omejene in temeljijo na hematološki in citogenetični odzivnosti.
This study included 7 patients with MDS/ MPD who were treated with Glivec 400 mg daily.
Ta študija je vključevala 7 bolnikov z MDS/ MPD, ki so bili zdravljeni z odmerkom zdravila Glivec 400 mg na dan.
In addition a further 24 patients with MDS/ MPD were reported in 13 publications.
Poleg tega so v 13 publikacijah poročali o nadaljnjih 24 bolnikih z MDS/ MPD.
21 patients were treated with Glivec 400 mg daily, while the other 3 patients received lower doses.
21 bolnikov je prejemalo zdravilo Glivec v odmerku 400 mg na dan, drugi 3 bolniki pa so prejemali nižje odmerke.
The same publication reported long term follow-up data from 12 MDS/ MPD patients with PDGFR gene rearrangements (5 patients from study B2225).
V isti publikaciji poročajo o podatkih z dolgoročnih kontrolnih pregledov za 12 bolnikov z MDS/ MPD s preureditvijo gena za PDGFR (5 bolnikov iz študije B2225).
These patients received Glivec for a median of 47 months (range 24 days – 60 months).
Ti bolniki so prejemali zdravilo Glivec mediano 47 mesecev (od 24 dni do 60 mesecev).
Eleven patients achieved rapid CHR; ten had complete resolution of cytogenetic abnormalities and a decrease
11 bolnikov je doseglo hiter popolni hematološki odziv, pri desetih je prišlo do popolne normalizacije citogenetičnih nepravilnosti in zmanjšanja oziroma izginotja fuzijskih transkriptov, kot so izmerili z verižno reakcijo s polimerazo v realnem času (RT- PCR).
19 or disappearance of fusion transcripts as measured by RT-PCR.
Hematološki odzivi so ostali enaki mediano 49 mesecev (od 19 do 60),
Haematological and cytogenetic responses have been sustained for a median of 49 months (range 19-60) and 47 months (range 16-59), respectively.
20 citogenetični odzivi pa 47 mesecev (od 16 do 59).
Clinical studies in HES/ CEL One open-label, multicentre, phase II clinical trial (study B2225) was conducted testing Glivec in diverse populations of patients suffering from life-threatening diseases associated with Abl, Kit or PDGFR protein tyrosine kinases.
Klinične študije pri HES/ CEL V enem odprtem multicentričnem kliničnem preskušanju faze II (študija B2225) so preskušali zdravilo Glivec pri različnih populacijah bolnikov z življensko ogrožujočimi boleznimi v povezavi z Abl, Kit ali PDGFR protein tirozin kinazami.
In this study, 14 patients with HES/ CEL were treated with 100 mg to 1,000 mg of Glivec daily.
V tej študiji je 14 bolnikov s HES/ CEL prejemalo od 100 mg do 1. 000 mg zdravila Glivec na dan.
A further 162 patients with HES/ CEL, reported in 35 published case reports and case series received Glivec at doses from 75 mg to 800 mg daily.
Nadaljnjih 162 bolnikov s HES/ CEL, o katerih so poročali v 35 objavljenih opisih primerov in skupinah primerov, je prejemalo zdravilo Glivec v odmerkih od 75 mg do 800 mg na dan.
In 61 of these 117 patients FIP1L1-PDGFRα fusion kinase was identified.
Pri 61 od teh 117 bolnikov so odkrili FIP1L1- PDGFRα fuzijsko kinazo.
An additional four HES patients were found to be FIP1L1-PDGFRα - positive in other 3 published reports.
FIP1L1- PDGFRα pozitivni so bili še štirje bolniki s HES, ki so jih opisovali v drugih 3 objavljenih poročilih.
All 65 FIP1L1-PDGFRα fusion kinase positive patients achieved a CHR sustained for months (range from 1+ to 44+ months censored at the time of the reporting).
Vseh 65 bolnikov z dokazano FIP1L1- PDGFRα fuzijsko kinazo je doseglo popolni hematološki odziv in ga ohranilo mesece (od več kot 1 mesec do več kot 44 mesecev, ocenjeno v času poročanja).
Improvements were reported in cardiac, nervous, skin/ subcutaneous tissue, respiratory/ thoracic/ mediastinal, musculoskeletal/ connective tissue/ vascular, and gastrointestinal organ systems.
Navajali so izboljšanje na področju srca, živčevja, kože/ podkožnega tkiva, dihalnega/ torakalnega/ mediastinalnega organskega sistema, mišičnoskeletnega/ vezivnotkivnega/ žilnega organskega sistema in prebavil.
Clinical studies in GIST One phase II, open-label, randomised, uncontrolled multinational study was conducted in patients with unresectable or metastatic malignant gastrointestinal stromal tumours (GIST).
Klinične študije pri GIST Eno odprto, randomizirano, nekontrolirano, večnacionalno študijo druge faze so opravili pri bolnikih z neresektabilnimi ali metastatičnimi malignimi gastrointestinalnimi stromalnimi tumorji (GIST).
In this study 147 patients were enrolled and randomised to receive either 400 mg or 600 mg orally once daily for up to 36 months.
V to študijo so vključili 147 bolnikov, ki so bili razporejeni po metodi naključne izbire, da so dobivali bodisi po 400 mg bodisi po 600 mg peroralno enkrat dnevno do 36 mesecev dolgo.
These patients ranged in age from 18 to 83 years old and had a pathologic diagnosis of Kit-positive malignant GIST that was unresectable and/ or metastatic.
Ti bolniki so bili stari od 18 do 83 let in so imeli patološko diagnozo Kit- pozitivnega malignega GIST, ki je bil neresektabilen in/ ali metastatičen.
Immunohistochemistry was routinely performed with Kit antibody (A-4502, rabbit polyclonal antiserum, 1:100; DAKO Corporation, Carpinteria, CA) according to analysis by an avidin-biotin-peroxidase complex method after antigen retrieval.
Imunohistokemijo so rutinsko opravljali s protitelesi Kit (A- 4502, kunčji poliklonalni antiserum, 1: 100; DAKO Corporation, Carpinteria, CA) v skladu z analizo z metodo avidin- biotin- peroksidaznega kompleksa po ponovni pridobitvi antigena.
Best tumour response in trial STIB2222 (GIST)
Najboljši tumorski odziv v preskušanju STIB2222
All doses (n=147) 400 mg (n=73) 600 mg (n=74)
Vsi odmerki (n=147) 400 mg (n=73) 600 mg (n=74)
Best response Complete response
najboljši odziv popoln odziv delni odziv stabilna bolezen
n (%) 1 (0.7)
n (%) 1 (0, 7) 98 (66, 7) 23 (15, 6)
Partial response Stable disease Progressive disease Not evaluable Unknown
napredujoča bolezen ni možno oceniti neznano
98 (66.7) 23 (15.6) 18 (12.2) 5 (3.4) 2 (1.4)
18 (12, 2) 5 (3, 4) 2 (1, 4)
patients who had stable disease at the time of the interim analysis achieved a partial response with longer treatment (median follow-up 31 months).
Pomembno število bolnikov, ki so imeli v času vmesne analize stabilno bolezen, je doseglo pri daljšem zdravljenju delni odziv (mediano obdobje spremljanja je bilo 31 mesecev).
12– 23).
Mediani čas do odziva je bil 13 tednov (95- odstotni interval zaupanja 12– 23).
Median time to treatment failure in responders was 122 weeks (95% C. I 106– 147), while in the overall study population it was 84 weeks (95% C. I 71– 109).
Mediani čas do neuspeha zdravljenja pri odzivnih bolnikih je bil 122 tednov (95- odstotni interval zaupanja 106– 147), medtem ko je bil pri celotni populaciji študije 84 tednov (95- odstotni interval zaupanja 71– 109).
The Kaplan-Meier estimate for survival after 36-month follow-up is 68%.
Kaplan- Meierjeva ocena za preživetje po 36- mesečnem spremljanju je 68%.
20 In two clinical studies (study B2222 and an intergroup study S0033) the daily dose of Glivec was escalated to 800 mg in patients progressing at the lower daily doses of 400 mg or 600 mg.
21 V dveh kliničnih študijah (študija B2222 in študija med skupinami S0033) so pri bolnikih, pri katerih je pri manjših dnevnih odmerkih 400 mg ali 600 mg, bolezen napredovala zvečali dnevni odmerek zdravila Glivec na 800 mg.
The daily dose was escalated to 800 mg in a total of 103 patients; 6 patients achieved a partial response and 21 stabilisation of their disease after dose escalation for an overall clinical benefit of 26%.
Dnevni odmerek so zvečali na 800 mg pri vsega skupaj 103 bolnikih; po zvečanju odmerka je 6 bolnikov doseglo delni odziv, 21 pa stabilizacijo svoje bolezni, kar je pomenilo celotno klinično koristnost 26%.
Clinical studies in DFSP One phase II, open label, multicentre clinical trial (study B2225) was conducted including 12 patients with DFSP treated with Glivec 800 mg daily.
Klinične študije pri protuberantnem dermatofibrosarkomu (DFSP) Eno odprto, multicentrično klinično preskušanje faze II (študija B2225) je vključevalo 12 bolnikov z DFSP, zdravljenih z zdravilom Glivec 800 mg na dan.
The median duration of therapy in study B2225 was 6.2 months, with a maximum duration of 24.3 months.
Mediano trajanje zdravljenja v študiji B2225 je bilo 6, 2 meseca z najdaljšim trajanjem 24, 3 mesece.
The adult patients reported in the published literature were treated with either 400 mg (4 cases) or 800 mg (1 case) Glivec daily.
Odrasli bolniki, o katerih so pisali v objavljeni literaturi, so bili zdravljeni z odmerki bodisi 400 mg (v 4 primerih) ali pa 800 mg (v 1 primeru) zdravila Glivec dnevno.
The paediatric patient received 400 mg/ m2/ daily, subsequently increased to 520 mg/ m2/ daily.
Pediatrični bolniki so prejemali po 400 mg/ m2/ dan, kasneje pa zvečan odmerek 520 mg/ m2/ dan.
The translocation t(17:22)[(q22: q13)], or its gene product, was present in nearly all responders to Glivec treatment.
Translokacija t( 17: 22) [(q22: q13)] oziroma njen genski produkt sta bila prisotna pri skoraj vseh bolnikih z odzivom na zdravljenje z zdravilom Glivec.
Pharmacokinetics of Glivec The pharmacokinetics of Glivec have been evaluated over a dosage range of 25 to 1,000 mg.
Farmakokinetika zdravila Glivec Farmakokinetiko zdravila Glivec so ovrednotili v območju odmerjanja od 25 do 1. 000 mg.
Absorption Mean absolute bioavailability for the capsule formulation is 98%.
Absorpcija Povprečna absolutna biološka uporabnost za zdravilo v obliki kapsul je 98%.
When given with a high-fat meal, the rate of absorption of imatinib was minimally reduced (11% decrease in Cmax and prolongation of tmax by 1.5 h), with a small reduction in AUC (7.4%) compared to fasting conditions.
Če so imanitib dajali z zelo mastnim obrokom, se je obseg njegove absorpcije minimalno zmanjšal (Cmax se je zmanjšala za 11%, tmax pa se je podaljšala za 1, 5 ure), AUC pa se je v primerjavi z razmerami na tešče malo zmanjšala (7, 4%).
Distribution At clinically relevant concentrations of imatinib, binding to plasma proteins was approximately 95% on the basis of in vitro experiments, mostly to albumin and alpha-acid-glycoprotein, with little binding to lipoprotein.
Porazdelitev Pri klinično pomembnih koncentracijah imatiniba je bila vezava na plazemske beljakovine na podlagi poskusov in vitro približno 95- odstotna, večina imatiniba se je vezala na albumine in kisli glikoprotein alfa, malo pa na lipoproteine.
Metabolism The main circulating metabolite in humans is the N-demethylated piperazine derivative, which shows similar in vitro potency to the parent.
Presnova Poglavitni po krvi krožeči presnovek pri ljudeh je N- demetilirani piperazinov derivat, ki kaže podobno potenco in vitro kot sama učinkovina.
The plasma AUC for this metabolite was found to be only 16% of the AUC for imatinib.
Ugotovili so, da je plazemska AUC tega presnovka samo 16% AUC imatiniba.
The plasma protein binding of the N-demethylated metabolite is similar to that of the parent compound.
Vezava N- demetiliranega presnovka na plazemske beljakovine je podobna kot pri izhodni spojini.
Imatinib and the N-demethyl metabolite together accounted for about 65% of the circulating radioactivity (AUC(0-48h)).
Imatinib in N- demetilirani presnovek sta skupaj prispevala okrog 65% radioaktivnosti v krvi (AUC( 0 - 48h)).
Of a panel of potential comedications (acetaminophen, aciclovir, allopurinol, amphotericin, cytarabine, erythromycin, fluconazole, hydroxyurea, norfloxacin, penicillin V) only erythromycin (IC50 50 µM) and fluconazole (IC50 118 µM) showed inhibition of imatinib metabolism which could have clinical relevance.
Od skupine možnih zdravil za sočasno uporabo (paracetamol, aciklovir, alopurinol, amfotericin, citarabin, eritromicin, flukonazol, hidroksisečnina, norfloksacin, penicilin V) sta samo eritromicin (IC50 50 µM) in flukonazol (IC50 118 µM) pokazala inhibicijo presnove imatiniba,
21 Imatinib was shown in vitro to be a competitive inhibitor of marker substrates for CYP2C9, CYP2D6 and CYP3A4/ 5.
In vitro so pokazali, da je imatinib kompetitiven inhibitor markerskih substratov za CYP2C9, CYP2D6 in CYP3A4/ 5.
Ki values in human liver microsomes were 27, 7.5 and 7.9 µmol/ l, respectively.
Vrednosti Ki v mikrosomih človeških jeter so bile 27, 7, 5 oziroma 7, 9 µmol/ l.
Maximal plasma concentrations of imatinib in patients are 2– 4 µmol/ l, consequently an inhibition of CYP2D6 and/ or CYP3A4/ 5-mediated metabolism of co-administered drugs is possible.
Največje koncentracije imatiniba v plazmi bolnikov so 2– 4 µmol/ l, zato je možna inhibicija sočasno uporabljanih zdravil s presnovo, ki poteka preko CYP2D6 in/ ali CYP3A4/ 5.
Imatinib did not interfere with the biotransformation of 5-fluorouracil, but it inhibited paclitaxel metabolism as a result of competitive inhibition of CYP2C8 (Ki = 34.7 µM).
Imatinib ni oviral biotransformacije 5- fluorouracila, je pa zaviral presnovo paklitaksela zaradi kompetitivne inhibicije CYP2C8 (Ki = 34, 7 µM).
This Ki value is far higher than the expected plasma levels of imatinib in patients, consequently no interaction is expected upon co- administration of either 5-fluorouracil or paclitaxel and imatinib.
Ta vrednost Ki je mnogo večja kot pričakovane plazemske koncentracije imatiniba pri bolnikih, zato po sočasnem dajanju bodisi 5- fluorouracila ali paklitaksela in imatiniba ni pričakovati medsebojnega delovanja.
Elimination Based on the recovery of compound(s) after an oral 14C-labelled dose of imatinib, approximately 81% of the dose was recovered within 7 days in faeces (68% of dose) and urine (13% of dose).
Izločanje iz telesa Na podlagi prestrezka spojin( e) po peroralnem odmerku imatiniba, označenega s 14C, se je približno 81% odmerka odstranilo iz telesa v 7 dneh z blatom (68% odmerka) in urinom (13% odmerka).
Unchanged imatinib accounted for 25% of the dose (5% urine, 20% faeces), the remainder being metabolites.
Nespremenjeni imatinib je predstavljal 25% odmerka (5% v urinu, 20% v blatu), preostanek pa so predstavljali presnovki.
Plasma pharmacokinetics Following oral administration in healthy volunteers, the t½ was approximately 18 h, suggesting that once-daily dosing is appropriate.
Plazemska farmakokinetika Po peroralnem dajanju zdravim prostovoljcem je bil t1/ 2 približno 18 ur, kar kaže na ustreznost enega odmerka na dan.
The increase in mean AUC with increasing dose was linear and dose proportional in the range of 25– 1,000 mg imatinib after oral administration.
Zvečevanje povprečne AUC z večanjem odmerka je bilo po peroralnem dajanju linearno in sorazmerno odmerku v območju 25– 1. 000 mg imatiniba.
There was no change in the kinetics of imatinib on repeated dosing, and accumulation was 1.5– 2.5-fold at steady state when dosed once daily.
Pri ponovnem odmerjanju se kinetika imatiniba ni spreminjala, kopičenje pa je bilo pri enem odmerku na dan v stanju dinamičnega ravnovesja 1, 5– 2, 5- kratno.
Pharmacokinetics in GIST patients In patients with GIST steady-state exposure was 1.5-fold higher than that observed for CML patients for the same dosage (400 mg daily).
Farmakokinetika pri bolnikih z GIST Pri bolnikih z GIST je bila izpostavljenost v stanju dinamičnega ravnovesja 1, 5- krat večja od tiste, ki je bila opazovana pri bolnikih s CML pri enakem odmerjanju (400 mg na dan).
Decreased values of albumin caused a reduced clearance (CL/ f); and higher levels of WBC led to a reduction of CL/ f.
Zmanjšane vrednosti albumina so povzročile zmanjšan očistek (CL/ f); višje koncentracije WBC pa so povzročile zmanjšanje CL/ f.
This change is not thought to be clinically significant.
Populacijska farmakokinetika Na podlagi analize populacijske farmakokinetike pri bolnikih s CML so ugotovili majhen učinek starosti na volumen porazdelitve (12- odstotno povečanje pri bolnikih, starejših od 65 let), vendar ta sprememba ni klinično pomembna.
The effect of bodyweight on the clearance of imatinib is such that for a patient weighing 50 kg the mean clearance is expected to be 8.5 l/ h, while for a patient weighing 100 kg the clearance will rise to 11.8 l/ h.
Vpliv telesne mase na očistek imatiniba je takšen, da je pri bolniku, ki tehta 50 kg, pričakovani povprečni očistek 8, 5 l/ h, pri bolniku, ki tehta 100 kg, pa se očistek poveča na 11, 8 l/ h.
Pharmacokinetics in children As in adult patients, imatinib was rapidly absorbed after oral administration in paediatric patients in both phase I and phase II studies.
Farmakokinetika pri otrocih Tako kot pri odraslih bolnikih, se je pri pediatričnih bolnikih v študijah tako prve kot druge faze imatinib po peroralni uporabi hitro absorbiral.
Dosing in children at 260 and 340 mg/ m2/ day achieved the same exposure, respectively, as doses of 400 mg and 600 mg in adult patients.
Odmerek 260 oziroma 340 mg/ m2 pri otrocih je dosegel enako izpostavljenost kot odmerek 400 mg oziroma 600 mg pri odraslih bolnikih.
The comparison of AUC(0-24) on day 8 and day 1 at the 340 mg/ m2/ day dose level revealed a 1.7-fold drug accumulation after repeated once-daily dosing.
Primerjava AUC( 0 - 2 24) 8. dne in 1. dne ob odmerku 340 mg/ m je pokazala 1, 7- kratno kopičenje zdravila po ponavljajočem se odmerjanju enkrat na dan.
Organ function impairment Imatinib and its metabolites are not excreted via the kidney to a significant extent.
Moteno delovanje organov Imatinib in njegovi presnovki se skozi ledvice ne izločajo v pomembni meri.
The increase is approximately 1.5- to 2-fold, corresponding to a 1.5-fold elevation of plasma AGP, to which imatinib binds strongly.
Gre za približno 1, 5 do 2- kratno zvišanje, ki ustreza 1, 5- kratnemu zvišanju alfa kislega proteina v plazmi, na katerega se imatinib močno veže.
The free drug clearance of imatinib is probably similar between patients with renal impairment and those with normal renal function, since renal excretion represents only a minor elimination pathway for imatinib (see sections 4.2 and 4.4).
Očistek nevezane učinkovine je pri imatinibu verjetno podoben pri bolnikih z okvaro ledvic in pri tistih z normalnim delovanjem ledvic, saj predstavlja izločanje skozi ledvice manj pomemben način izločanja za imatinib (glejte poglavji 4. 2 in 4. 4).
Although the results of pharmacokinetic analysis showed that there is considerable inter-subject variation, the mean exposure to imatinib did not increase in patients with varying degrees of liver dysfunction as compared to patients with normal liver function (see sections 4.2, 4.4 and 4.8).
23 Čeprav so rezultati farmakokinetične analize pokazali, da so razlike med posamezniki precejšnje, se povprečna izpostavljenost imatinibu pri bolnikih z različnimi stopnjami disfunkcije jeter v primerjavi z bolniki z normalno funkcijo jeter ni povečala (glejte poglavja 4. 2, 4. 4 in 4. 8).
22 5.3 Preclinical safety data
5. 3 Predklinični podatki o varnosti
Multiple dose toxicity studies revealed mild to moderate haematological changes in rats, dogs and monkeys, accompanied by bone marrow changes in rats and dogs.
Pri podganah in psih so jih spremljale spremembe v kostnem mozgu.
Mild to moderate increases in transaminases and slight decreases in cholesterol, triglycerides, total protein and albumin levels were observed in both species.
Pri obeh živalskih vrstah so opazili blago do zmerno zvišanje transaminaz in rahlo znižanje koncentracij holesterola, trigliceridov, celotnih beljakovin in albuminov.
In rats, hyperplasia of the transitional epithelium in the renal papilla and in the urinary bladder was observed at doses ≥ 6 mg/ kg in the 13-week study, without changes in serum or urinary parameters.
Pri podganah so v 13- tedenski študiji pri odmerkih ≥ 6 mg/ kg našli hiperplazijo prehodnega epitela v ledvični papili in v sečnem mehurju, brez sprememb serumskih ali urinskih parametrov.