natgillin/translations-raw huggingface dataset:
The most commonly reported adverse drug reactions associated with Gemzar treatment include: nausea with or without vomiting, raised liver transaminases (AST/ALT) and alkaline phosphatase, reported in approximately 60% of patients; proteinuria and haematuria reported in approximately 50% patients; dyspnoea reported in 10-40% of patients (highest incidence in lung cancer patients); allergic skin rashes occur in approximately 25% of patients and are associated with itching in 10% of patients.
Najpogosteje poročani neželeni učinki povezani z zdravilom Gemzar vključujejo: navzeo z ali brez bruhanja, zvišane jetrne transaminaze (AST/ ALT) in alkalna fosfataza, o katerih so poročali pri približno 60% bolnikov; proteinurija in hematurija, o katerih so poročali pri približno 50% bolnikov; dispneja, o kateri so poročali pri 10- 40% bolnikov (z najvišjo incidenco pri bolnikih s karcinomom pljuč); alergijski izpuščaji so se pojavili pri približno 25% bolnikov, pri 10% bolnikov so ti izpuščaji srbeči.
The frequency and severity of the adverse reactions are affected by the dose, infusion rate and intervals between doses (see section 4.4).
Na pogostnost in hudost neželenih učinkov vplivajo odmerek, hitrost infuzije in intervali med odmerki (glejte poglavje 4. 4).
Dose-limiting adverse reactions are reductions in thrombocyte, leucocyte and granulocyte counts (see section 4.2).
Neželeni učinki, zaradi katerih je treba odmerek omejiti, so znižanja koncentracij trombocitov, levkocitov in granulocitov (glejte poglavje 4. 2).
Very common (≥1/10), Common (≥1/100 to < 1/10), Uncommon (≥1/1000 to < 1/100), Rare (≥1/10,000 to < 1/1000), Very Rare (< 1/10,000).
Podatki iz kliničnih preskušanj Pogostnosti so določene kot: zelo pogosto (≥ 1/ 10), pogosto (≥ 1/ 100 do < 1/ 10), občasno (≥ 1/ 1. 000 do < 1/ 100), redko (≥ 1/ 10. 000 do < 1/ 1. 000), zelo redko (< 1/ 10. 000).
System Organ Class Blood and lymphatic system disorders
Razred organskega sistema Bolezni krvi in limfatičnega sistema
Bone-marrow suppression is usually mild to moderate and mostly affects the granulocyte count (see section 4.2) • Thrombocytopaenia • Anaemia
Skupina pogostnosti Zelo pogosto • Levkopenija (nevtropenija 3. stopnje = 19, 3%; 4. stopnje = 6%) Zaviranje kostnega mozga je običajno blago do zmerno in prizadane zlasti koncentracijo granulocitov (glejte poglavje 4. 2) • Trombocitopenija • Anemija
Common • Febrile neutropaenia Very rare • Thrombocytosis
Pogosto • Febrilna nevtropenija.
Immune system disorders
24 Zelo redko • Trombocitoza Bolezni imunskega sistema
Common • Headache • Insomnia • Somnolence
Pogosto • Glavobol • Zaspanost • Nespečnost
24 System Organ Class Respiratory, thoracic and mediastinal disorders
Bolezni dihal, prsnega koša in mediastinalnega prostora
Frequency grouping Very common • Dyspnoea –usually mild and passes rapidly without treatment
Zelo pogosto • Dispneja - zlasti blaga in mine hitro brez zdravljenja
Common • Cough • Rhinitis
Pogosto • Kašelj • Rinitis
Uncommon • Interstitial pneumonitis (see section 4.4) • Bronchospasm –usually mild and transient but may require parenteral treatment Gastrointestinal disorders
Občasno • Interstiticijski pnevmonitis • Bronhospazem - zlasti blag in prehoden, vendar bo morda potrebno peroralno zdravljenje
Very common • Vomiting • Nausea
Bolezni prebavil
Hepatobiliary disorders
Zelo pogosto • Bruhanje • Navzea
Common • Increased bilirubin
Pogosto • Diareja • Stomatitis in razjede v ustih • Zaprtje
Very common • Allergic skin rash frequently associated with pruritus • Alopecia
Zelo pogosto • Zvišane jetrne transaminaze (AST in ALT) in alkalna fosfataza
Common • Itching • Sweating
Pogosto • Zvišan bilirubin
Ulceration Vesicle and sore formation Scaling
Redko • Zvišana gama- glutamil transferaza (GGT) Bolezni kože in podkožja
Very rare • Severe skin reactions, including desquamation and bullous skin eruptions Musculoskeletal and connective tissue disorders
Zelo pogosto • Alergijski srbenjem
Common • Back pain • Myalgia
kožni izpuščaj, pogosto s
System Organ Class Renal and urinary disorders
Alopecija
Frequency grouping Very Common • Haematuria • Mild proteinuria
Pogosto • Srbenje • Znojenje
General disorders and administration site conditions
Redko • Tvorba razjed • Tvorba mehurjev in ran • Luščenje
Cough, rhinitis, malaise, perspiration and sleeping difficulties have also been reported. • Oedema/peripheral oedema- including facial oedema.
Zelo redko • Hude kožne reakcije, vključno z luščenjem in buloznimi kožnimi vzbrstmi Bolezni mišično- skeletnega sistema in vezivnega tkiva
Common • Fever • Asthenia • Chills
Pogosto • Bolečine v hrbtu • Mialgija
Rare
Bolezni sečil
•
Splošne težave in spremembe na mesta aplikacije
Injection site reactions-mainly mild in nature
Edem je običano revezibilen po prekinitvi zdravljenja.
Injury, poisoning, and procedural Complications
Pogosto • Vročina • Astenija • Mrzlica
Radiation toxicity (see section 4.5).
Obsevalna toksičnost (glejte poglavje 4. 5).
Postmarketing experience (spontaneous reports) frequency not known (can’t be estimated from the available data)
Izkušnje v obdobju trženja zdravila (spontana poročila) katerih pogostnost ni znana (ocena iz danih podatkov ni možna)
Cardiac disorders Arrythmias, predominantly supraventricular in nature Heart failure
26 Srčne bolezni Aritmije, zlasti supraventrikularne Srčno popuščanje
Respiratory, thoracic and mediastinal disorders Pulmonary oedema Adult respiratory distress syndrome (see section 4.4)
Bolezni dihal, prsnega koša in mediastinalnega prostora Pljučni edem Sindrom dihalne stiske pri odraslem (glejte poglavje 4. 4)
Gastrointestinal disorders Ischaemic colitis
Bolezni prebavil Ishemični kolitis
Skin and subcutaneous tissue disorders Severe skin reactions, including desquamation and bullous skin eruptions, Lyell’s Syndrome, Steven- Johnson Syndrome
Bolezni kože in podkožja Hude kožne reakcije, vključno z luščenjem in buloznimi kožnimi vzbrstmi, Lyellov sindrom, Steven - Johnsonov sindrom
26 Renal and urinary disorders Renal failure (see section 4.4) Haemolytic uraemic syndrome (see section 4.4)
Bolezni sečil Ledvično popuščanje (glejte poglavje 4. 4) Hemolitično uremični sindrom (glejte poglavje 4. 4)
Combination use in breast cancer The frequency of grade 3 and 4 haematological toxicities, particularly neutropaenia, increases when gemcitabine is used in combination with paclitaxel.
27 Kombinirana uporaba za karcinom dojke Pogostnost 3. in 4. stopnje hematološke toksičnosti, zlasti nevtropenije je povečana, kadar se gemcitabin uporablja v kombinaciji s paklitakselom.
Grade 3 and 4 Adverse Events Paclitaxel versus gemcitabine plus paclitaxel
Neželeni učinki 3. in 4. stopnje Paklitaksel proti gemcitabinu s paklitakselom
Number (%) of Patients
Število (%) bolnikov
Paclitaxel arm
Veja s paklitakselom (N=259)
Gemcitabine plus
Veja z gemcitabinom in paklitakselom (N=262)
Laboratory
Laboratorijski
Grade 4 Grade 3
3. stopnja 4. stopnja 3. stopnja
Grade 4
4.
5 (1.9) 0
stopnja
1 (0.4) 15 (5.7) 0 14 (5.3)
Anemija Trombocitopenija Nevtropenija Ne- laboratorijski
3 (1.1) 1 (0.4)
5 (1, 9) 1 (0, 4) 15 (5, 7) 0 0 14 (5, 3) 11 (4, 2) 17 (6, 6) * 82 (31, 3)
3 (1.2)
3 (1, 1) 1 (0, 4) 45 (17, 2) *
12 (4.6)
Febrilna nevtropenija Utrujenost Diareja Motorična nevtropenija Senzorna nevtropenija
3 (1.2) 5 (1.9)
3 (1, 2) 0 12 (4, 6) 3 (1, 2) 1 (0, 4) 15 (5, 7) 5 (1, 9) 0 8 (3, 1) 2 (0, 8) 0 6 (2, 3) 9 (3, 5) 0 14 (5, 3)
1 (0.4) 0
1 (0, 4) 2 (0, 8) 0 1 (0, 4) 1 (0, 4)
0.8) 0
* Nevtropenija 4. stopnje, ki je trajala več kot 7 dni, se je pojavila pri 12, 6% bolnikov v veji s kombinacijo in pri 5, 0% bolnikov v veji z paklitakselom.
27 Combination use in bladder cancer
Kombinirana uporaba za karcinom sečnega mehurja
MVAC (methotrexate, vinblastine, doxorubicin and cisplatin) arm (N=196)
Veja z MVAC (metotreksat, vinblastin,
Laboratory
doksorubicin in cisplatin) (N=196)
Grade 3
Laboratorijski
Anaemia Thrombocytopaenia Non-laboratory
Anemija Trombocitopenija Ne- laboratorijski
4(2) 47(24) 25(13) 57(29)
30 (16) 4 (2) 47 (24) 15 (8) 25 (13) 57 (29)
Nausea and vomiting Diarrhoea Infection Stomatitis
Navzea in bruhanje Diareja Vnetje Stomatitis
3(2) 44(22) 1(1) 6(3) 10(5) 4(2) 8(4) 2(1)
37 (19) 3 (2) 44 (22) 15 (8) 1 (1) 6 (3) 19 (10) 10 (5) 4 (2) 34 (18) 8 (4) 2 (1)
Combination use in ovarian cancer
28 Kombinirana uporaba za karcinom jajčnika
Grade 3 and 4 Adverse Events Carboplatin versus Gemcitabine plus carboplatin Number (%) of Patients
Neželeni učinki 3. in 4. stopnje Karboplatin proti gemcitabinu s karboplatinom Število (%) bolnikov
Carboplatin arm (N=174)
Veja s karboplatinom (N=174)
Gemcitabine plus carboplatin arm (N=175)
Veja z gemcitabinom in karboplatinom (N=175)
Grade 3
3.
Grade 4 Grade 3
stopnja 4. stopnja 3. stopnja
Anaemia
stopnja
10(5.7)
Anemija
39(22.3)
10 (5, 7) 4 (2, 3) 39 (22, 3)
9(5.1)
9 (5, 1)
Neutropaenia
Nevtropenija Trombocitopenija Levkopenija
19(10.9)
19 (10, 9) 18 (10, 3) 11 (6, 3)
2(1.1)
2 (1, 1) 2 (1, 1) 1 (0, 6)
Thrombocytopaenia
73 (41, 7) 53 (30, 3) 84 (48, 0)
18(10.3)
50 (28, 6) 8 (4, 6) 9 (5, 1)
53(30.3)
Ne- laboratorijski
Leucopaenia
Hemoragija Febrilna nevtropenija
84(48.0)
0 (0, 0) 0 (0, 0)
9 (5.1)
0 (0) 0 (0)
(0.0)
(0, 0) (0. 0)
Febrile neutropaenia
Infekcija brez nevtropenije
Sensory neuropathy was also more frequent in the combination arm than with single agent carboplatin
Senzorna nevropatija je bila tudi bolj pogosta v veji kombinacije kot pri samostojnemu karboplatinu.
Doses as high as 5700 mg/m2 have been administered by intravenous infusion over 30-minutes every 2 weeks with clinically acceptable toxicity.
Odmerki do 5. 700 mg/ m2 površine telesa dani z intravensko infuzijo v 30 minutah vsake 2 tedna imajo klinično sprejemljivo toksičnostjo.
Pharmacotherapeutic group: pyrimidine analogues ATC code:
Farmakoterapevtska skupina: analogi pirimidinskih baz, oznaka ATC:
Cytotoxic activity in cell cultures Gemcitabine shows significant cytotoxic effects against a variety of cultured murine and human tumour cells.
Citotoksična aktivnost v celičnih kulturah Gemcitabin kaže značilne citotoksične učinke proti številnim kulturam glodalskih in humanih tumorskih celic.
Its action is phase-specific such that gemcitabine primarily kills cells that are undergoing DNA synthesis (S-phase) and, under certain circumstances, blocks the progression of cells at the junction of the G1/S phase boundary.
Njegovo delovanje je fazno- specifično, tako da gemcitabin primarno ubija celice, ki so v fazi sinteze DNK (S- fazi) in, pod določenimi pogoji blokira razvoj celic v stiku med mejo G1/ S faze.
Antitumoral activity in preclinical models In animal tumour models, antitumoural activity of gemcitabine is schedule-dependent.
Protitumorska aktivnost v predkliničnih modelih V živalskih modelih tumorjev je protitumorska aktivnost gemcitabina odvisna od sheme zdravljenja.
If, however, gemcitabine is given every third or fourth day, it can be administered in non- lethal doses with substantial antitumoural activity against a broad spectrum of mouse tumours.
Če pa gemcitabin dajemo vsak tretji ali četrti dan, ga lahko dajemo v neletalnih odmerkih z znatno protitumorsko aktivnostjo proti širokemu spektru mišjih tumorjev.
Mechanism of action Cellular metabolism and mechanism of action:
Mehanizem delovanja Celična presnova in mehanizem delovanja:
Gemcitabine (dFdC), which is a pyrimidine antimetabolite, is metabolised intracellularly by nucleoside kinase to the active diphosphate (dFdCDP) and triphosphate (dFdCTP) nucleosides.
Gemcitabin (dFdC), ki je pirimidinski antipresnovek, znotrajcelično presnavlja nukleozidna kinaza do aktivnih difosfatnih (dFdCDP) - in trifosfatnih (dFdCTP) nukleozidov.
The cytotoxic effect of gemcitabine is due to inhibition of DNA synthesis by two mechanisms of action by dFdCDP and dFdCTP.
Citotoksični učinek gemcitabina je posledica zaviranja sinteze DNK z dvema mehanizmoma
Second, dFdCTP competes with dCTP for incorporation into DNA (self-potentiation).
Nato dFdCTP tekmuje z dCTP za vgrajevanje v DNK (samo- ojačitev).
Clinical data Bladder cancer A randomised phase III study of 405 patients with advanced or metastatic urothelial transitional cell carcinoma showed no difference between the two treatment arms, gemcitabine/cisplatin versus methotrexate/vinblastine/adriamycin/cisplatin (MVAC), in terms of median survival (12.8 and 14.8 months respectively, p=0.547), time to disease progression (7.4 and 7.6 months respectively, p=0.842) and response rate (49.4% and 45.7% respectively, p=0.512).
Klinični podatki Karcinom sečnega mehurja Randomizirana študija faze III s 405 bolniki z napredovalim ali metastatskim urotelijskim karcinomom tranzicijskih celic ni pokazala nobene razlike med dvema vejama zdravljenja, gemcitabin/ cisplatin proti metotreksat/ vinblastin/ adriamicin/ cisplatin (MVAC) glede povprečnega preživetja (12, 8 in oziroma 14, 8 mesecev, p=0, 547), časa do napredovanja bolezni (7, 4 in oziroma 7, 6 mesecev, p=0, 842) ter stopnje odziva (49, 4% in 45, 7%, p=0, 512).
Pancreatic cancer In a randomised phase III study of 126 patients with advanced or metastatic pancreatic cancer, gemcitabine showed a statistically significant higher clinical benefit response rate than 5-fluorouracil (23.8% and 4.8% respectively, p=0.0022).
Karcinom trebušne slinavke V randomizirani študiji faze III s 126 bolniki z napredovalim ali metastatskim karcinomom trebušne slinavke, je gemcitabin pokazal značilno višjo stopnjo odziva klinične koristi kot 5- fluorouracil (23, 8% in oziroma 4, 8%, p=0, 0022).
Also, a statistically significant prolongation of the time to progression from 0.9 to 2.3 months (log-rank p < 0.0002) and a statistically significant prolongation of median survival from 4.4 to 5.7 months (log-rank p < 0.0024) was observed in patients treated with gemcitabine compared to patients treated with 5-fluorouracil.
Pri bolnikih, zdravljenih z gemcitabinom so v primerjavi z bolniki, zdravljenimi s 5 - fluorouracilom opazili tudi značilno podaljšanje časa do napredovanja bolezni od 0, 9 do 2, 3 mesecev (logaritemska stopnja p < 0, 0002) ter statistično značilno podaljšanje povprečnega preživetja od 4, 4 do 5, 7 mesecev (logaritemska stopnja p < 0, 0024).
29 Non small cell lung cancer In a randomised phase III study of 522 patients with inoperable, locally advanced or metastatic NSCLC, gemcitabine in combination with cisplatin showed a statistically significant higher response rate than cisplatin alone (31.0% and 12.0%, respectively, p < 0.0001).
Nedrobnocelični karcinom pljuč V randimizirani študiji faze III s 522 bolnikov z neoperabilnim, lokalno napredovalim ali metastatskim nedrobnoceličnim karcinomom pljuč, je gemcitabin s cisplatinom pokazal statistično značilno višjo stopnjo odziva kot sam cisplatin (31, 0% in oziroma 12, 0%, p < 0, 0001).
A statistically significant prolongation of the time to progression, from 3.7 to 5.6 months (log-rank p < 0.0012) and a statistically significant prolongation of median survival from 7.6 months to 9.1 months (log-rank p < 0.004) was observed in patients treated with gemcitabine/cisplatin compared to patients treated with cisplatin.
Pri bolnikih, zdravljenih z gemcitabinom/ cisplatinom so v primerjavi z bolniki, zdravljenimi s cisplatinom opazili statistično značilno podaljšanje časa do napredovanja bolezni od 3, 7 do 5, 6 mesecev (logaritemska stopnja p < 0, 0012) ter statistično značilno podaljšanje povprečnega preživetja od 7, 6 mesecev do 9, 1 mesecev (logaritemska stopnja p < 0, 004).
In another randomised phase III study of 135 patients with stage IIIB or IV NSCLC, a combination of gemcitabine and cisplatin showed a statistically significant higher response rate than a combination of cisplatin and etoposide (40.6% and 21.2%, respectively, p=0.025).
V drugi randomizirani študiji faze III s 135 bolniki s stopnjo IIIB ali IV nedrobnoceličnega karcinoma pljuč je kombinacija gemcitabina in cisplatina pokazala statistično značilno višjo stopnjo odziva kot kombinacija cisplatina in etopozida (40, 6% in oziroma 21, 2%, p=0, 025).
A statistically significant prolongation of the time to progression, from 4.3 to 6.9 months (p=0.014) was observed in patients treated with gemcitabine/cisplatin compared to patients treated with etoposide/cisplatin.
Pri bolnikih, zdravljenih z gemcitabinom/ cisplatinom so v primerjavi z bolniki, zdravljenimi z etopozidom/ cisplatinom opazili ststistično značilno podaljšanje časa do napredovanja bolezni od 4, 3 do 6, 9 mesecev (p=0, 014).
Ovarian carcinoma In a randomised phase III study, 356 patients with advanced epithelial ovarian carcinoma who had relapsed at least 6 months after completing platinum based therapy were randomised to therapy with gemcitabine and carboplatin (GCb), or carboplatin (Cb).
Karcinom jajčnika V randomizirani študiji faze III s 365 bolniki z napredovalim epitelijskim karcinomom jajčnika, ki so imeli relaps najmanj 6 mesecev po zaključeni terapiji na osnovi platine, so bili randomizirani na terapijo z gemcitabinom in karboplatinom (GCb) ali karboplatinom (Cb).
A statistically significant prolongation of the time to progression of disease, from 5.8 to 8.6 months (log-rank p= 0.0038) was observed in the patients treated with GCb compared to patients treated with Cb.
Pri bolnikih, zdravljenih z GCb so v primerjavi z bolniki, zdravljenimi z Cb opazili statistično značilno podaljšanje časa do napredovanja bolezni od 5, 8 do 8, 6 mesecev (logaritemska stopnja p=0, 0038).
Differences in response rate of 47.2% in the GCb arm versus 30.9% in the Cb arm (p=0.0016) and median survival 18 months (GCb) versus 17.3 (Cb) (p=0.73) favoured the GCb arm.
Razlike v stopnji odziva v veji GCb 47, 2% proti veji Cb 30, 9% (p=0, 0016) ter povprečnega preživetja 18 mesecev (GCb) proti 17, 3 (Cb) (p=0, 73) so bile v korist veje GCb.
Breast cancer In a randomised phase III study of 529 patients with inoperable, locally recurrent or metastatic breast cancer with relapse after adjuvant/neoadjuvant chemotherapy, gemcitabine in combination with paclitaxel showed a statistically significant prolongation of time to documented disease progression from 3.98 to 6.14 months (log-rank p=0.0002) in patients treated with gemcitabine/paclitaxel compared to patients treated with paclitaxel.
30 Karcinom dojke V randomizirani študiji faze III s 529 bolniki z neoperabilnim, lokalno ponavljajočim ali metastatskim karcinomom dojke z relapsom po dopolnilni/ novi dopolnilni kemoterapiji je gemcitabin v kombinaciji s paklitakselom pri bolnikih zdravljenih s gemcitabin/ paklitaksel v primerjavi z bolniki, zdravljenimi s paklitakselom pokazal statistično značilno podaljšanje časa do dokumentiranega napredovanja bolezni od 3, 98 do 6, 14 mesecev (logaritemska stopnja p=0, 0002).
After 377 deaths, the overall survival was 18.6 months versus 15.8 months (log rank p=0.0489, HR 0.82) in patients treated with gemcitabine/paclitaxel compared to patients treated with paclitaxel and the overall response rate was 41.4% and 26.2% respectively (p= 0.0002).
Po 377 smrtih je bilo pri bolnikih, zdravljenih z gemcitabin/ paklitaksel v primerjavi z bolniki, zdravljenimi s paklitakselom celotno preživetje 18, 6 mesecev proti 15, 8 mesecev (logaritemska stopnja p=0, 0489, HR 0, 82,) ter celotna stopnja odziva 41, 4% in oziroma 26, 2% (p=0, 0002).
Of these patients, approximately 45% had non-small cell lung cancer and 35% were diagnosed with pancreatic cancer.
Od teh bolnikov jih je približno 45% imelo nedrobnocelični karcinom pljuč in 35% karcinom trebušne slinavke.
The following pharmacokinetic parameters were obtained for doses ranging from 500 to 2,592 mg/m2 that were infused from 0.4 to 1.2 hours.
Naslednje farmakokinetične parametre so pridobili iz odmerkov v razponu med 500 in 2. 592 mg/ m2 površine telesa, ki so bili infundirani med 0, 4 in 1, 2 ure.
Peak plasma concentrations (obtained within 5 minutes of the end of the infusion) were 3.2 to 45.5 µg/ml.
Najvišje plazemske koncentracije (dosežene v 5 minutah po koncu infuzije) so bile 3, 2 in 45, 5 µg/ ml.
Plasma concentrations of the parent compound following a dose of 1,000 mg/m2/30-minutes are greater than 5 µg/ml for approximately 30-minutes after the end of the infusion, and greater than 0.4 µg/ml for an additional hour.
Plazemske koncentracije osnovne učinkovine po odmerku 1. 000 mg/ m2 površine telesa/ 30- minut so višje kot 5 µg/ ml približno 30 minut po koncu infuzije ter višje kot 0, 4 µg/ ml v nadaljnji uri.
Distribution The volume of distribution of the central compartment was 12.4 l/m2 for women and 17.5 l/m2 for men (inter-individual variability was 91.9%).
Porazdelitev Volumen porazdelitve osrednjega dela je bil 12, 4 l/ m2 površine telesa za ženske in 17, 5 l/ m2 površine telesa za moške.
The volume of distribution of the peripheral compartment was 47.4 l/m2.
(variabilnost med posamezniki je bila 91, 9%).
The volume of the peripheral compartment was not sensitive to gender.
Volumen porazdelitve perifernega dela je bila 47, 4 l/ m2 površine telesa.
Half-life:
Razpolovni čas:
This ranged from 42 to 94 minutes depending on age and gender.
V razponu od 42 in 94 minut, odvisno od starosti in spola.
30 Metabolism Gemcitabine is rapidly metabolised by cytidine deaminase in the liver, kidney, blood and other tissues.
Presnova Gemcitabin se hitro presnavlja s citidinsko aminazo v jetrih, ledvicah, krvi in drugih tkivih.
The primary metabolite, 2'-deoxy-2', 2'-difluorouridine (dFdU), is not active and is found in plasma and urine.
Primarni presnovek 2 '- dezoksi- 2', 2 '- difluoruridin (dFdU) ni aktiven in ga najdemo v plazmi in urinu.
Excretion Systemic clearance ranged from 29.2 l/hr/m2 to 92.2 /hr/m2 depending on gender and age (inter-individual variability was 52.2%).
Izločanje Sistemski očistek je bil v razponu od 29, 2 l/ h/ m2 površine telesa do 92, 2 l/ h/ m2 površine telesa, odvisno od spola in starosti (variabilnost med posamezniki je bila 52, 2%).
Clearance for women is approximately 25% lower than the values for men.
Očistek pri ženskah je bil približno 25% nižji kot vrednosti pri moških.
For the recommended gemcitabine dose of 1000 mg/m2 given as a 30-minute infusion, lower clearance values for women and men should not necessitate a decrease in the gemcitabine dose.
Pri priporočenem odmerku gemcitabina 1. 000 mg/ m2 površine telesa, danega kot 30- minutna infuzija, zmanjšan očistek gemcitabina pri ženskah in moških ne zahteva znižanja odmerka gemcitabina.
Less than 10% is excreted as unchanged drug.
Izločanje z urinom: manj kot 10% se izloči v obliki nespremenjenega zdravila.
Renal clearance was 2 to 7 l/hr/m2.
Ledvični očistek je bil 2 do 7 l/ h/ m2 površine telesa.
During the week following administration, 92 to 98% of the dose of gemcitabine administered is recovered, 99% in the urine, mainly in the form of dFdU and 1% of the dose is excreted in faeces.
V tednu po dajanju gemcitabina se izloči 92 do 98% odmerka gemcitabina, 99% z urinom, zlasti v obliki dFdU in 1% z blatom.
dFdCTP kinetics This metabolite can be found in peripheral blood mononuclear cells and the information below refers to these cells.
31 Farmakokinetika dFdCTP Ta presnovek najdemo v enojedrnih celicah periferne krvi in spodnji podatki se nanašajo na te celice.
Intracellular concentrations increase in proportion to gemcitabine doses of 35-350 mg/ m2/30-minutes, which give steady state concentrations of 0.4-5 µg/ml.
Znotrajcelične koncentracije naraščajo skladno z odmerki gemcitabina 35 do 350 mg/ m2 površine telesa/ 30- minut, kar daje koncentracije v stanju dinamičnega ravnovesja 0, 4- 5 µg/ ml.
At gemcitabine plasma concentrations above 5 µg/ml, dFdCTP levels do not increase, suggesting that the formation is saturable in these cells.
Pri plazemskih koncentracijah gemcitabina nad 5 µg/ ml, se raven dFdCTP ne zviša, kar kaže, da v teh celicah lahko pride do nasičenja.
Half-life of terminal elimination:
Končni razpolovni čas izločanja:
0.7-12 hours.
0, 7 - 12 ur.
dFdU kinetics Peak plasma concentrations (3-15 minutes after end of 30-minute infusion, 1000 mg/m2):
Farmakokinetika dFdU Najvišje plazemske koncentracije (3- 15 minut po koncu 30- minutne infuzije, 1. 000 mg/ m2 površine telesa):
Trough concentration following once weekly dosing:
Najnižja koncentracija po odmerjanju enkrat tedensko:
0.07-1.12 µg/ml, with no apparent accumulation.
0, 07- 1, 12 µg/ ml, brez očitnega kopičenja.