natgillin/translations-raw huggingface dataset:
Common: dyspnoea, epistaxis Rare: pleural effusion, lung fibrosis
Občasni: tromboflebitis, hipertenzija, tromboza
Very rare*: cough, pulmonary hypertension
Zelo redki *: šok
Gastrointestinal disorders:
Bolezni dihal, prsnega koša in mediastialnega prostora:
Very common: nausea, vomiting, diarrhoea, mucosal inflammation, constipation, stomatitis, abdominal pain
Pogosti: dispneja, epistaksa Redki: plevralni izliv, pljučna fibroza
Common: dry mouth, mouth ulceration, melaena, dyspepsia
Zelo redki *: kašelj, pljučna hipertenzija
Hepatobiliary disorders:
Bolezni prebavil:
Very rare*: hepatic necrosis, hepatic encephalopathy
Zelo pogosti: slabost, bruhanje, diareja, vnetje sluznice,
8
8 zaprtje, stomatitis, bolečine v trebuhu
Skin and subcutaneous tissue disorders:
Pogosti: suha usta, rane v ustih, melena, dispepsija
Very common: alopecia Common: transient skin change, dry skin, exfoliative dermatitis, pruritis, rash, acne, transient and mild nail changes
Zelo redki *: obstrukcija črevesa, perforacija črevesa, psevdomembranski kolitis, ishemični kolitis, mezenterična tromboza, nekrotični enterokolitis, ezofagitis, ascites, akutni pankreatitis
Uncommon: changes in nail pigmentation or discoloration of nail bed
Bolezni jeter, žolčnika in žolčevodov:
Rare*: erythema
Bolezni kože in podkožja:
Very rare*:
Zelo pogosti: alopecija
Musculoskeletal and connective tissue disorders:
Pogosti: prehodne spremembe na koži, suha koža, eksfoliativni dermatitis, izpiščaj, osip, akne, prehodne in blage spremembe na nohtih
Very common: arthralgia, myalgia Common: bone pain, leg cramps, myasthenia, back pain
Občasni: spremembe v pigmentaciji nohtov ali spremembe barve nohtnega ležišča
Renal and urinary disorders:
Redki *: eritem
Common: dysuria
Zelo redki *:
General disorders and administration site conditions:
Bolezni mišično- skeletnega sistema in vezivnega tkiva:
Very common: asthenia, pain, oedema including peripheral and face
Zelo pogosti: artralgija, mijalgija Pogosti: bolečine v kosteh, krči v nogah, mijastenija, bolečine v križu
Common: mild injection site reactions (erythema, tenderness, skin discoloration or swelling, pain, extravasation, can result in cellulitis and skin ulceration), malaise, chest pain, chills, pyrexia
Zelo pogosti: astenija, bolečine, edem vključno z perifernim edemom in edemom lica Pogosti: blage reakcije na mestu injiciranja (eritem, občutljivost, spremembe barve kože ali otekline, bolečine, ekstravazacija, pa tudi celulitis in rane na koži), neugodje, bolečine v prsnem košu, mrzlica, pireksija
Combination therapy
9 Kombinirano zdravljenje
The following discussion refers to two major trials for the first-line chemotherapy of ovarian cancer (paclitaxel + cisplatin: over 1050 patients) and two Phase III trials for the treatment of advanced NSCLC (paclitaxel + cisplatin: over 360 patients) (see section 5.1).
Naslednja razprava se nanaša na dve večji preskušanji zdravljenja prvega izbora raka jajčnikov s kemoterapijo (paklitaksel + cisplatin: več kot 1050 bolnikov) in dve preskušanji faze III za zdravljenje napredovalega nedrobnoceličnega karcinoma pljuč (paklitaksel + cisplatin: več kot 360 bolnikov) (glejte poglavje 5. 1).
When administered as a 3 hour infusion for the first-line chemotherapy of ovarian cancer, neurotoxicity, arthralgia/ mayalgia, and hypersensitivity were reported as more frequent and severe by patients treated with paclitaxel followed by cisplatin than patients treated with cyclophosphamide followed by cisplatin.
Pri uporabi v obliki 3 urne infuzije kot kemoterapija prvega izbora pri zdravljenju raka jajčnikov so pri bolnikih, ki so jih zdravili najprej s paklitakselom in nato s cisplatinom, poročali o pogostejši ter hujši nevrotoksičnosti, artralgiji/ mialgiji in preobčutljivosti kot pri bolnikih, ki so jih zdravili s ciklofosfamidom in nato s cisplatinom.
Myelosuppression appeared to be less frequent and severe with paclitaxel as a 3 hour infusion followed by cisplatin compared with cyclophosphamide followed by cisplatin.
Mielosupresija je bila pri uporabi paklitaksela v obliki 3 urne infuzije, ki ji je sledil cisplatin, redkejša in manj huda kot pri ciklofosfamidu, ki mu je sledil cisplatin.
Neurotoxicity, mainly peripheral neuropathy, appeared to be more frequent and severe with a 175 mg/ m2 3 hour infusion (85% neurotoxicity, 15% severe) than with a 135 mg/ m2 24 hour infusion (25% peripheral neuropathy, 3% severe) when paclitaxel was combined with cisplatin.
Pri kombinaciji paklitaksela in cisplatina je bila nevrotoksičnost, večinoma periferna nevropatija, pogostejša in hujša pri 3- urni infuziji 175 mg/ m2 (85% nevrotoksičnost, 15% huda) kot pri 24 urni infuziji 135 mg/ m2 (25% periferalna nevropatija, 3% huda).
9 In eight published clinical trials (8 Phase III trials) including 4735 patients with advanced ovarian cancer and in twelve published clinical trials (one large Phase II and eleven Phase III trials) including 4315 NSCLC patients treated with paclitaxel and platinum-containing regimens, similar undesirable effects were observed compared to single-agent paclitaxel treatment.
V osmih objavljenih kliničnih preskušanjih (8 preskušanjih faze III), v katerih je sodelovalo 4735 bolnis z napredovalim rakom jajčnikov, in v dvanajstih objavljenih kliničnih preskušanjih (eno veliko preskušanje faze II in enajst preskušanj faze III), v katerih je sodelovalo 4315 bolnikov z nedrobnoceličnim karcinomom pljuč, ki so jih zdravili s paklitakselom in pripravki, ki vsebujejo platino, so opazili podobne neželene učinke kot pri samostojnem zdravljenju s paklitakselom.
Additionally ileus, effects on creatinine clearance, abnormal electrolytes (e. g. hyponatremia, hypomagnesemia), hyperglycaemia, cough and pneumonia occurred very rarely.
Poleg tega so se ileus, učinki na očistek kreatinina, nenormalne koncentracije elektrolitov (npr. hiponatremija, hipomagnezemija), hiperglikemija, kašelj in pljučnica pojavili zelo redko.
Pneumonitis in patients receiving concomitant radiotherapy and/ or gemcitabine has been reported very rarely.
O pnevmonitisu so pri bolnikih, ki so prejemali sočasno zdravljenje z obsevanjem in/ ali gemcitabinom, poročali zelo redko.
AIDS related Kaposi’ s sarcoma
Kaposijev sarkom, povezan z aidsom:
The following undesirable effects relate to 107 AIDS-KS patients treated with 100 mg/ m2 Paxene administered as a 3 hour infusion as second-line chemotherapy in a clinical study, and were considered possibly or probably related to Paxene.
Navedeni neželeni učinki se nanašajo na 107 bolnikov z AIDS- KS, pri katerih so v klinični študiji kot kemoterapijo drugega izbora uporabili 100 mg/ m2 Paxena v obliki 3 urne infuzije, in za katere menijo, da so morebiti ali verjetno povezani s Paxenom.
Except for haematological and hepatic events (see below), generally the frequency and severity of undesirable effects in AIDS-KS patients were similar to those noted in patients with other solid tumours treated with paclitaxel monotherapy.
Razen hematoloških učinkov in učinkov na jetra (glejte spodaj), sta bili pogostost in resnost neželenih učinkov pri bolnikih z AIDS- KS podobni kot pri bolnikih z drugimi trdnimi tumorji, ki so jih samostojno zdravili s paklitakselom.
Bone marrow suppression was the major dose-limiting toxicity of Paxene.
Supresija kostnega, ozga je glavna toksičnost, ki omejuje velikost odmerka Paxena.
Severe neutropenia (< 500 cells/ mm3) occurred in 20% and 39% of patients during the first course of treatment and the entire treatment period respectively.
Huda nevtropenija (< 500 celic/ mm3) se je v prvem krogu zdravljenja pojavila pri 20% bolnikov, med celotnim zdravljenjem pa pri 39% bolnikov.
Neutropenia was present for > 7 days in 41% and for 30-35 days in 8% of patients.
Nevtropenijo je 41% bolnikov imelo manj kot 7 dni, 8% bolnikov pa 30- 35 dni.
The incidence of Grade 4 neutropenia lasting 7 days or more was 22%.
Incidenca nevtropenije 4. stopnje, ki je trajala sedem dni ali več, je bila 22- odstotna.
Neutropenic fever related to Paxene was reported in 14% of patients.
O nevtropenični mrzlici, povezani s Paxenom, so poročali pri 14% bolnikov.
There were three septic episodes (2.8%) during Paxene administration related to the medicinal product that proved fatal.
Med dajanjem Paxena je zaradi uporabe tega zdravila prišlo do treh usodnih septičnih epizod (2, 8%).
Thrombocytopenia was observed in 50% of patients, and was severe (< 50,000 cells/ mm3) in 9%.
Trombocitopenijo so opazili pri 50% bolnikov, pri 9% teh bolnikov pa je bila huda (< 50. 000 celic/ mm3).
Bleeding episodes related to Paxene were reported in < 3% of patients and bleeding was localised.
O krvavitvah, povezanih z uporabo Paxena, so poročali pri manj kot 3% bolnikov, krvavitve pa so bile lokalne.
Anaemia (Hb < 11 g/ dL) was observed in 61% of patients and was severe (Hb < 8 g/ dL) in 10%.
Anemijo (Hb < 11 g/ dl) so opazili pri 61% bolnikov, pri 10% teh bolnikov pa je bila anemija huda (Hb < 8 g/ dl).
Red cell transfusions were required in 21% of patients.
Pri 21% bolnikov je bila potrebna transfuzija rdečih krvnih celic.
Among patients (> 50% on protease inhibitors) with normal baseline liver function, 28%, 43% and 44% had elevations in bilirubin, alkaline phosphatase and AST (SGOT), respectively.
Med bolniki (> 50% jih je prejemalo zaviralce proteaz) z normalno izhodiščno jetrno funkcijo, je 28% bolnikov imelo povišan bilirubin, 43% povišano alkalno fosfatazo in 44% povišane vrednosti AST (SGOT).
For each of these parameters, the increases were severe in 1% of cases.
Do hujšega povečanja pri vsakem od teh parametrov je prišlo v 1% primerov.
4.9 Overdose
10 4. 9 Preveliko odmerjanje
Antineoplastic agents (taxanes), ATC code:
Farmakoterapevtska skupina: zdravila z delovanjem na novotvorbe (taksani), Oznaka ATC:
Metastatic breast cancer:
Metastatski rak dojke:
10 The efficacy and safety of Paxene (175 mg/ m² over 3 hours at 3-week intervals) in refractory metastatic breast cancer were investigated in 172 women in a multicentre, open-label Phase III trial.
Varnost in učinkovitost zdravila Paxene (175 mg/ m² aplicirano v 3 urah vsake 3 tedne) pri neodzivnem metastatskem raku dojke so preučevali pri 172 ženskah v multicentričnem, odprtem preskušanju III. faze.
The clinical response rate was 18.5%, median time to progression was 2.8 months (CI:
Klinični delež odgovorov je bil 18, 5%, mediana časa do napredovanja bolezni je bila 2, 8 meseca (CI:
2.1 - 3.3 months) and the median survival time was 9.9 months (CI:
2, 1 – 3, 3 meseca), mediana preživetja pa je bila 9, 9 meseca (CI:
7.8 - 13.1 months).
7, 8 - 13, 1 meseca).
Advanced ovarian cancer (first-line treatment):
Napredovali rak jajčnikov (zdravljenje prvega izbora):
The efficacy and safety of paclitaxel were evaluated in two major, randomised, controlled trials (vs. cyclophosphamide 750 mg/ m2/ cisplatin 75 mg/ m2).
Učinkovitost in varnost paklitaksela so ocenili v dveh večjih randomiziranih, nadzorovanih preskušanjih (v primerjavi s 750 mg/ m2 ciklofosfamida/ 75 mg/ m2 cisplatina).
In the first trial, over 650 patients with stage IIb-c, III or IV primary ovarian cancer received a maximum of 9 treatment courses of paclitaxel (175 mg/ m2 over 3 hours) followed by cisplatin (75 mg/ m2) or control.
V prvem preskušanju je več kot 650 bolnic s primarnim rakom jajčnikov faze IIb- c, III ali IV prejelo največ 9 krogov zdravljenja s paklitakselom (175 mg/ m2 v 3 urah) in nato cisplatin (75 mg/ m2) ali kontrolo.
The second major trial evaluated a maximum of 6 courses of either paclitaxel (135 mg/ m² over 24 hours) followed by cisplatin (75 mg/ m²) or control in over 400 patients with stage III/ IV primary ovarian cancer, with a > 1 cm residual disease after staging laparotomy, or with distant metastases.
V drugem večjem preskušanju so pri več kot 400 bolnicah s primarnim rakom jajčnikov faze III/ IV, z a > 1 - centimetrsko osnovno boleznijo po lapratomiji ali z oddaljenimi metastazami, ocenili do 6 krogov zdravljenja s paklitakselom (135 mg/ m2 v 24 urah) in nato cisplatinom (75 mg/ m2) ali kontrolo.
Although the two different paclitaxel posologies were not compared with each other directly, in both trials patients treated with paclitaxel in combination with cisplatin had a significantly longer time to progression (Study 1: median 15.3 months vs 11.5 months, p < 0.001; Study 2: median 17 months vs 13 months, p < 0.001), and longer survival time (Study 1: median 36 months vs 26 months, p= 0.0016; Study 2: median 36 months vs 24 months, p < 0.001), and in Study 1 a significantly higher response rate (Study 1:
Čeprav teh dveh odmerjanj paklitaksela niso neposredno primerjali med seboj, je bil pri obeh preskušanjih pri bolnikih, ki so jih zdravili s paklitakselom v kombinaciji s cisplatinom, čas do progresije daljši (študija 1: mediana 15, 3 meseca v primerjavi z 11, 5 meseca, p < 0, 001; študija 2: mediana 17 mesecev v primerjavi s 13 meseci, p < 0, 001), in obdobje preživetja je bilo daljše (študija 1: mediana 36 mesecev v primerjavi s 26 meseci, p = 0, 0016; študija 2: mediana 36 mesecev v primerjavi s 24 meseci, p < 0, 001), v študiji 1 pa je bila stopnja odzivnosti značilno večja (študija 1:
59% vs 45%, p= 0.014; Study 2:
59% v primerjavi 45%, p = 0, 014; študija 2:
60% vs 50%, NS), when compared with standard therapy.
60% v primerjavi s 50%, NS) v primerjavi s standardnim zdravljenjem.
Increased neurotoxicity, arthralgia/ myalgia but reduced myelosuppression were observed in advanced ovarian cancer patients administered 3 hour infusion paclitaxel/ cisplatin as compared to patients who received cyclophosphamide/ cisplatin.
Pri bolnicah z napredovalim rakom jajčnikov, ki so jim dajali 3 urno infuzijo paklitaksela/ cisplatina, so v primerjavi z bolniki, ki so prejemali ciklofosfamid/ cisplatin, opazili povečano nevrotoksičnost in artralgijo/ mialgijo ter zmanjšano mielosupresijo.
Metastatic ovarian cancer (second-line treatment):
Metastatski rak jajčnika (zdravljenje drugega izbora):
The efficacy and safety of Paxene (175 mg/ m² over 3 hours repeated at 3-week intervals) in advanced metastatic ovarian cancer were investigated in 120 women in a multicentre, open-label extended Phase II trial.
Varnost in učinkovitost zdravila Paxene (175 mg/ m² aplicirano v 3 urah vsake 3 tedne) pri napredovalem metastatskem raku jajčnika so preučevali pri 120 ženskah v multicentričnem, odprtem preskušanju III. faze.
The clinical response rate was 21.7% (CI:
Klinični delež odgovorov je bil 21, 7% (CI:
14.7 - 31.1%), median time to progression was 4.1 months (CI:
14, 7 - 31, 1%), mediana časa do napredovanja bolezni je bila 4, 1 meseca (CI:
3.3 - 4.9 months) and the median survival time was 13.4 months (CI:
3, 3 - 4, 9 mesecev), mediana čas preživetja pa je bila 13, 4 meseca (CI:
11.5 - 15.0 months).
11, 5 - 15, 0 mesecev).
Advanced non-small cell lung carcinoma:
11 Napredovali nedrobnocelični karcinom pljuč:
Efficacy of paclitaxel/ cisplatin combination has been demonstrated in two randomised, controlled trials in patients with locally advanced or metastatic NSCLC.
Učinkovitost kombinacije paklitaksela in cisplatina so pokazali pri bolnikih z lokalno napredovalimi ali metastaziranimi nedrobnoceličnim karcinomom pljuč v dveh randomiziranih, nadzorovanih preskušanjih.
There was no advantage in survival (9.5 vs.
V prvi študiji so naključno razporedili 332 bolnikov z lokalno napredovalim ali metastaziranim nedrobnoceličnim karcinomom pljuč tako, da so prejemali cisplatin (80 mg/ m2) v kombinaciji s tenipozidom (100 mg/ m2; n= 166), ali cisplatin (80 mg/ m2) in paklitaksel (175 mg/ m2; n= 166).
5.0 months) with cisplatin/ paclitaxel vs cisplatin/ tenoposide.
Pri primerjavi cisplatina/ paklitaksela in cisplatina/ tenopozida ni bilo prednosti pri preživetju (9, 5 v primerjavi z 9, 9 meseca) ali preživetja brez progresije (5, 1 v primerjavi s 5, 0 meseci).
26%), lesser overall side effects and improved short term QoL with cisplatin/ paclitaxel vs cisplatin/ tenoposide were considered important results in a palliative population.
Vendar so večja stopnja odzivnosti (37% v primerjavi s 26%), manjši skupni neželeni učinki in izboljšana kratkoročna kakovost življenja pri cisplatinu/ paklitakselu kot pri cisplatinu/ tenopozidu pomembni rezultati pri paliativni populaciji.
6%).
Periferna nevrotoksičnost 2. in 3. stopnje je bila pri cisplatinu/ paklitakselu pogostejša (29% v primerjavi s 6%).
In the second study, 599 patients with stage IIIB or IV disease were randomised to receive cisplatin (75 mg/ m2) and etoposide (100 mg/ m2; n= 200), or cisplatin (75 mg/ m2) and low-dose paclitaxel (135 mg/ m2; n= 198), or cisplatin (75 mg/ m2) and high-dose paclitaxel (250 mg/ m2) with G-CSF (n= 201).
V drugi študiji so naključno razporedili 599 bolnikov s stopnjo bolezni IIIB ali IV tako, da so prejemali cisplatin (75 mg/ m2) in etopozid (100 mg/ m2; n= 200), ali cisplatin (75 mg/ m2) ter majhne odmerke paklitaksela (135 mg/ m2; n= 198) ali pa cisplatin (75 mg/ m2) in velike odmerke paklitaksela (250 mg/ m2) z G- CSF (n= 201).
Median survival for each paclitaxel-containing arm was not significantly different compared to etoposide/ cisplatin (p= 0.097 and 0.090 for high-dose paclitaxel and low-dose paclitaxel, respectively).
Mediana preživetja v vseh skupinah, ki so prejemale paklitaksel, ni bila značilno različna od tistih, ki so prejemale etopozid/ cisplatin (p= 0, 097 za skupino, ki je prejemala velik odmerek paklitaksela, in 0, 090 za skupino, ki je prejemala majhen odmerek paklitaksela).
With respect to progression free survival, highly statistically significant results were noted for the high-dose paclitaxel arm compared to etoposide/ cisplatin (p= 0.007).
Pri preživetju brez progresije so pri skupini, ki je prejemala paklitaksel, v primerjavi s skupino, ki je prejemala etopozid/ cisplatin, opazili statistično zelo značilne rezultate (p= 0, 007).
Response rates strongly favoured the paclitaxel-containing arms [13%, 30% and 26% for the etoposide/ cisplatin, high-dose paclitaxel (p < 0.001 vs etoposide/ cisplatin) and low-dose paclitaxel regimens (p= 0.003 vs
Stopnje odzivnosti so bile bistveno boljše pri skupinah, ki so prejemale paklitaksel [13% pri skupini, ki je prejemala etopozid/ cisplatin, 30% pri skupini, ki je prejemala velike odmerke paklitaksela (p < 0, 001 v primerjavi s skupino, ki je prejemala etopozid/ cisplatin), in 26% pri skupini, ki je prejemala majhne odmerke paklitaksela (p= 0, 003 v primerjavi s skupino, ki je prejemala etopozid/ cisplatin)].
21%).
Vendar je nevrotoksičnost 3. stopnje bila značilno pogostejša pri skupini, ki je prejemala velike odmerke paklitaksela (40%), kot pri skupini, ki je prejemala etopozid/ cisplatin (21%).
AIDS-related Kaposi’ s sarcoma:
Kaposijev sarkom, povezan z aidsom:
The efficacy and safety of Paxene were investigated in a single, non-comparative study in 107 patients with advanced KS, previously treated with systemic chemotherapy.
Učinkovitost in varnost Paxena so raziskovali v eni sami, neprimerjalni študiji na 107 bolnikih z napredovalim Kaposijevim sarkomom, ki so se prej zdravili s sistemsko kemoterapijo.
In the study, the majority of patients were administered granulocyte colony stimulating factor (G-CSF).
V študiji so večini bolnikov dali granulocitne kolonije stimulirajoči faktor (G- CSF).
Patients were given a 3 hour infusion of Paxene 100 mg/ m² administered every 14 days.
Bolniki so vsakih 14 dni prejeli 3- urno infuzijo Paxena 100 mg/ m2.
The overall success rate (complete or partial response) after 15 cycles of treatment was 57% (CI 44 – 70%) in liposomal anthracycline-resistant patients.
Skupna stopnja uspešnosti (popoln ali delni odziv) po 15 krogih zdravljenja pri bolnikih, odpornih proti liposomskim antraciklinom, je bila 57- odstotna (CI 44 – 70%).
In liposomal anthracycline-resistant patients, the response rates were comparable for patients who had never received a protease inhibitor (55.6%) and those who received one at least 2 months prior to treatment with Paxene (60.9%).
Pri bolnikih, odpornih proti liposomskim antraciklinom, so bile stopnje odzivnosti primerljive s stopnjami pri tistih bolnikih, ki niso nikoli prejemali proteaznih inhibitorjev (55, 6%), in pri tistih, ki so ga prejeli vsaj dva meseca pred zdravljenjem s Paxenom (60, 9%).
The median time to progression in the core population was 468 days (95% CI 257-NE).
Srednja vrednost do stopnjevanja pri glavni populaciji je bila 468 dni (95% CI 257- NE).
Median survival for Paxene could not be computed, but the lower 95% bound was 617 days in core patients.
Srednje vrednosti preživetja pri uporabi Paxena ni bilo mogoče določiti, sicer pa je bila pri glavni skupini bolnikov spodnja meja 95- odstotna, torej 617 dni.
Based on in vitro studies, the degree of plasma protein binding has been reported to range from 88 to 98%.
12 Na osnovi študij in vitro so poročali, da je stopnja vezave na plazemske beljakovine med 88 in 98%.
Pharmacokinetic parameters of paclitaxel at 175 mg/ m2 given over 3 hours in 13 patients with breast cancer were as follows: maximum concentration (Cmax) was 3,890 ng/ ml, area under the plasma concentration vs. time curve (AUClast) was 14,090 ng·h/ ml and clearance (CL) was 13.3 l/ h/ m2.
Farmakokinetični parametri paklitaksela pri odmerku 175 mg/ m2, apliciranem v 3 urah 13 bolnicam z rakom dojke, so bili naslednji: največja koncentracija (Cmax) je bila 3. 890 ng/ ml, površina pod krivuljo plazemskih koncentracij v odvisnosti od časa (AUClast) je bila 14. 090 ng· h/ ml, očistek (CL) pa 13, 3 l/ h/ m2.
Metastatic breast or ovarian cancer:
Metastatski rak dojke ali jajčnika:
Pharmacokinetic parameters of paclitaxel at 175 mg/ m2 given over 3 hours in 5 patients with breast cancer and 3 patients with ovarian cancer were as follows: maximum concentration (Cmax) was 4,213 ng/ ml, area under the plasma concentration vs. time curve (AUClast) was 12,603 ng·h/ ml and clearance (CL) was 20.4 l/ h/ m2.
Farmakokinetični parametri paklitaksela pri odmerku 175 mg/ m2, apliciranem v 3 urah 5 bolnicam z rakom dojke in 3 bolnicam z rakom jajčnika, so bili naslednji: največja koncentracija (Cmax) je bila 4. 213 ng/ ml, površina pod krivuljo plazemskih koncentracij v odvisnosti od časa (AUClast) je bila 12. 603 ng· h/ ml, očistek (CL) pa 20, 4 l/ h/ m2.
Renal excretion plays a minor role in the elimination of paclitaxel, less than 10% of the dose has been reported to be excreted in the urine as unchanged drug.
Ekskrecija preko ledvic igra pri izločanju paklitaksela majhno vlogo; poročali so, da se manj kot 10% odmerka izloči v nespremenjeni obliki z urinom.
The major elimination pathway is metabolism followed by biliary excretion; in six patients 39% to 87% of an intravenous dose (175 mg/ m2) was excreted in faeces and, on average, only 10% of the dose was excreted as unchanged paclitaxel.
Pri šestih bolnikih se je 39% do 87% intravenskega odmerka (175 mg/ m2) izločilo z blatom, samo 10% odmerka pa se je v povprečju izločilo v obliki nespremenjenega paklitaksela.
Several metabolites have been detected, but only three of them have been identified:
Zaznali so več presnovkov, od katerih so identificirali le tri:
6 alpha-hydroxypaclitaxel, 3’ -para-hydroxypaclitaxel and 6 alpha, 3’ -para-dihydroxypaclitaxel.
6 alfa- hidroksipaklitaksel, 3 '- para- hidroksipaklitaksel in 6 alfa- 3' - para- dihidroksipaklitaksel.
6 alpha-hydroxypaclitaxel is the major component excreted in faeces.
6 alfa- hidroksipaklitaksel je glavna spojina, ki se izloča z blatom.
In vitro studies have shown that CYP2C8 and 3A4 are involved in the formation of 6 alpha-hydroxypaclitaxel and 3’ -para-dihydroxypaclitaxel, respectively.
Študije in vitro so pokazale, da pri tvorbi 6 alfa- hidroksipaklitaksela sodeluje CYP2C8, pri tvorbi 3 '- para- hidroksipaklitaksela pa CYP3A4.