natgillin/translations-raw huggingface dataset:
Events reported during the infusion were primarily episodes of hypertension; events reported within 24 hours of finishing an infusion were headache and skin reactions (rash, urticaria).
Učinki, opisani med infuzijo, so bile predvsem epizode hipertenzije, učinki, opisani v 24 urah po koncu infundiranja, pa so bili glavobol in kožne reakcije (izpuščaj, urtikarija).
The rate of anaphylactic reactions (occurring in a total of 6/ 3,778 patients, 0.2%) was several fold higher with the 4 mg/ kg dose, compared to the 8 mg/ kg dose.
Delež anafilaktičnih reakcij (ki so se pojavile pri skupaj 6 od 3778 bolnikov, 0, 2%) je bil pri odmerku 4 mg/ kg nekajkrat večji kot pri odmerku 8 mg/ kg.
Clinically significant hypersensitivity reactions associated with tocilizumab and requiring treatment discontinuation were reported in a total of 13 out of 3,778 patients (0.3%) treated with tocilizumab during the controlled and open label clinical studies.
Klinično pomembne preobčutljivostne reakcije, ki so bile povezane z uporabo tocilizumaba in so zahtevale prekinitev zdravljenja, so zabeležili pri skupaj 13 od 3778 bolnikov (0, 3%), ki so v kontroliranih in odprtih kliničnih študijah dobivali tocilizumab.
These reactions were generally observed during the second to fifth infusions of tocilizumab (see section 4.4).
Te reakcije so se praviloma pojavile med drugo do peto infuzijo tocilizumaba (glejte poglavje 4. 4).
Immunogenicity A total of 2,876 patients have been tested for anti-tocilizumab antibodies in the controlled clinical trials.
Imunogenost V kontroliranih kliničnih preskušanjih so protitelesa proti tocilizumabu preverili pri skupaj 2876 bolnikih.
Of the 46 patients (1.6%) who developed anti-tocilizumab antibodies, 6 had an associated medically significant hypersensitivity reaction, of which 5 led to permanent discontinuation of treatment.
Od 46 bolnikov (1, 6%), pri katerih so se pojavila protitelesa proti tocilizumabu, jih je 6 imelo spremljajočo klinično pomembno preobčutljivostno reakcijo, ki je v 5 primerih vodila v ukinitev zdravljenja.
In 30 patients (1.1%) who developed neutralising antibodies, no apparent correlation to clinical response was observed.
Pri 30 bolnikih (1, 1%), pri katerih so se pojavila nevtralizacijska protitelesa, niso opazili povezave tega s kliničnim odzivom.
Haematological abnormalities Decreases in neutrophil counts below 1 x 109/ l occurred in 3.4% of patients on tocilizumab 8 mg/ kg plus DMARDs compared to < 0.1% of patients on placebo plus DMARDs.
Hematološke nepravilnosti Število nevtrofilcev se je zmanjšalo pod 1 x 109/ l pri 3, 4% bolnikov, ki so dobivali 8 mg/ kg tocilizumaba v kombinaciji z imunomodulirajočimi antirevmatičnimi zdravili, in pri < 0, 1% bolnikov, ki so dobivali placebo v kombinaciji z imunomodulirajočimi antirevmatičnimi zdravili.
Approximately half of the patients who developed an ANC < 1 x 109/ l did so within 8 weeks after starting therapy.
Med bolniki, ki se jim je absolutno število nevtrofilcev zmanjšalo na < 1 x 109/ l, se je to pri približno polovici zgodilo v 8 tednih po začetku zdravljenja.
Decreases below 0.5 x 109/ l were reported in 0.3% patients receiving tocilizumab 8 mg/ kg plus DMARDs.
O zmanjšanju pod 0, 5 x 109/ l so poročali pri 0, 3% bolnikov, ki so dobivali 8 mg/ kg tocilizumaba v kombinaciji z imunomodulirajočimi antirevmatičnimi zdravili.
There was no clear association between decreases in neutrophils and the occurrence of serious infections.
Med zmanjšanjem števila nevtrofilcev in pojavljanjem resnih okužb ni bilo jasne povezanosti.
Decreases in platelet counts below 100 x 103/ μ l occurred in 1.7% of patients on tocilizumab 8 mg/ kg plus DMARDs compared to < 1% on placebo plus DMARDs.
Število trombocitov se je zmanjšalo pod 100 x 103/ µl pri 1, 7% bolnikov, ki so dobivali 8 mg/ kg tocilizumaba v kombinaciji z imunomodulirajočimi antirevmatičnimi zdravili, in pri < 1% tistih, ki so
8 Hepatic transaminase elevations Transient elevations in ALT/ AST > 3 x ULN were observed in 2.1% of patients on tocilizumab 8 mg/ kg compared to 4.9% of patients on MTX and in 6.5% of patients who received 8 mg/ kg tocilizumab plus DMARDs compared to 1.5% of patients on placebo plus DMARDs.
Zvišanje jetrnih transaminaz Prehodno zvišanje ALT/ AST na > 3- kratno ZMN so zabeležili pri 2, 1% bolnikov, ki so dobivali 8 mg/ kg tocilizumaba, pri 4, 9% bolnikov, ki so dobivali metotreksat, pri 6, 5% bolnikov, ki so dobivali 8 mg/ kg tocilizumaba v kombinaciji z imunomodulirajočimi antirevmatičnimi zdravili, ter pri 1, 5% tistih, ki so dobivali placebo v kombinaciji z imunomodulirajočimi antirevmatičnimi zdravili.
MTX) to tocilizumab monotherapy resulted in increased frequency of these elevations.
Če so monoterapiji s tocilizumabom dodali potencialno hepatotoksična zdravila (npr. metotreksat), se je pogostnost teh zvišanj povečala.
Elevations of ALT/ AST > 5 x ULN were observed in 0.7% of tocilizumab monotherapy patients and 1.4% of tocilizumab plus DMARD patients, the majority of whom were discontinued permanently from tocilizumab treatment.
Zvišanje ALT/ AST na > 5- kratno ZMN so opažali pri 0, 7% bolnikov, ki so dobivali tocilizumab v monoterapiji, in pri 1, 4% bolnikov, ki so tocilizumab dobivali v kombinaciji z imunomodulirajočimi antirevmatičnimi zdravili; pri večini teh so zdravljenje s tocilizumabom ukinili.
Lipid parameters During the six month controlled trials, increases of lipid parameters such as total cholesterol, triglycerides, LDL cholesterol, and/ or HDL cholesterol have been reported commonly.
Vrednosti lipidov Med šestmesečnimi kontroliranimi preskušanji je bil pogosto opisan porast vrednosti lipidov, npr. celotnega holesterola, trigliceridov, holesterola LDL in/ ali holesterola HDL.
Approximately 24% of patients receiving RoActemra in clinical trials experienced sustained elevations in total cholesterol ≥ 6.2 mmol/ l, with 15% experiencing a sustained increase in LDL to ≥ 4.1 mmol/ l.
Pri približno 24% bolnikov, ki so v kliničnih preskušanjih dobivali zdravilo RoActemra, se je pojavilo dolgotrajno zvišanje celotnega holesterola na ≥ 6, 2 mmol/ l, pri 15% pa dolgotrajno zvišanje LDL na ≥ 4, 1 mmol/ l.
Malignancies The clinical data are insufficient to assess the potential incidence of malignancy following exposure to tocilizumab.
Malignomi Kliničnih podatkov za oceno možne incidence malignomov po izpostavljenosti tocilizumabu ni dovolj.
One case of accidental overdose was reported in which a patient with multiple myeloma received a single dose of 40 mg/ kg.
Opisan je en primer naključnega prevelikega odmerjanja, pri katerem je bolnik z multiplim mielomom dobil 40 mg/ kg v enem odmerku.
No serious adverse reactions were observed in healthy volunteers who received a single dose up to 28 mg/ kg, although dose limiting neutropenia was observed.
Pri zdravih prostovoljcih, ki so dobili posamične odmerke do 28 mg/ kg, ni bilo resnih neželenih učinkov, opazili pa so nevtropenijo, ki je omejila odmerek.
Immunosupressants, Interleukin inhibitors; ATC code:
Farmakoterapevtska skupina: zdravila za zaviranje imunske odzivnosti, zaviralci interlevkinov; oznaka ATC:
Mechanism of action Tocilizumab binds specifically to both soluble and membrane-bound IL-6 receptors (sIL-6R and mIL-6R).
Mehanizem delovanja Tocilizumab se specifično veže na topne in membransko vezane receptorje za IL- 6 (sIL- 6R in mIL - 6R).
Tocilizumab has been shown to inhibit sIL-6R and mIL-6R-mediated signalling.
Ugotovljeno je, da tocilizumab zavira signaliziranje prek sIL- 6R in mIL- 6R.
IL-6 is a pleiotropic pro-inflammatory cytokine produced by a variety of cell types including T- and B-cells, monocytes and fibroblasts.
IL- 6 je pleiotropen proinflamatoren citokin, ki nastaja v različnih vrstah celic, med drugim v celicah T in B, monocitih in fibroblastih.
IL-6 is involved in diverse physiological processes such as T-cell activation, induction of immunoglobulin secretion, induction of hepatic acute phase protein synthesis and stimulation of haemopoiesis.
IL- 6 je vpleten v različna fiziološka dogajanja, npr. aktiviranje celic T, indukcijo sekrecije imunoglobulinov, indukcijo jetrne sinteze beljakovin akutne faze in stimulacijo hematopoeze.
IL-6 has been implicated in the pathogenesis of diseases including inflammatory diseases, osteoporosis and neoplasia.
IL- 6 je domnevno vpleten v patogenezo nekaterih bolezni, med drugim vnetnih bolezni, osteoporoze in neoplazem.
Increases in haemoglobin levels were observed, through tocilizumab decreasing the IL-6 driven effects on hepcidin production to increase iron availability.
Opažali so povečanje koncentracije hemoglobina, ker tocilizumab zmanjša učinke IL- 6 na nastajanje hepcidina
9 Clinical efficacy The efficacy of tocilizumab in alleviating the signs and symptoms of RA was assessed in five randomised, double-blind, multi-centre studies.
Pri bolnikih, ki so dobivali tocilizumab, so ugotovili zmanjšanje koncentracije CRP v normalno območje že 2. teden, ohranilo pa se je ves čas zdravljenja.
Studies I-V enrolled patients ≥ 18 years of age with active RA diagnosed according to the American College of Rheumatology (ACR) criteria and who had at least eight tender and six swollen joints at baseline.
Študije od I do V so zajele bolnike, stare ≥ 18 let, ki so imeli aktiven revmatoidni artritis, diagnosticiran po merilih Ameriškega revmatološkega združenja ACR (American College of Rheumatology) in so imeli izhodiščno vsaj osem bolečih in šest oteklih sklepov.
The primary endpoint for each of the five studies was the proportion of patients who achieved an ACR 20 response at week 24.
Primarni opazovani dogodek petih študij je bil delež bolnikov, ki so po 24 tednih dosegli odziv ACR 20.
The majority (67%) of patients were MTX-naïve.
Večina bolnikov (67%) dotlej še ni dobivala metotreksata.
Doses of 8 mg/ kg of tocilizumab were given every four weeks as monotherapy.
Tocilizumab so uporabljali kot monoterapijo v odmerku 8 mg/ kg na štiri tedne.
The comparator group was weekly MTX (dose titrated from 7.5 mg to a maximum of 20 mg weekly over an eight week period).
Primerjalna skupina so bili bolniki, ki so tedensko dobivali metotreksat (odmerek so jim prilagajali od 7, 5 mg do največ 20 mg na teden v obdobju osmih tednov).
Study II, a two year study with planned analyses at week 24 and week 52, evaluated 1196 patients who had an inadequate clinical response to MTX.
Študija II je bila dveletna študija z načrtovano analizo v 24. in 52. tednu, ocenila je 1196 bolnikov z nezadostnim kliničnim odzivom na metotreksat.
Doses of 4 or 8 mg/ kg of tocilizumab or placebo were given every four weeks as blinded therapy for 52 weeks in combination with stable MTX (10 mg to 25 mg weekly).
Odmerke 4 ali 8 mg/ kg tocilizumaba ali placebo so dobivali 52 tednov na štiri tedne kot slepljeno terapijo v kombinaciji s stabilnim odmerkom metotreksata (od 10 do 25 mg na teden).
The primary endpoint at week 24 was the proportion of patients who achieved an ACR 20 response.
Primarna končna točka v 24. tednu je bil delež bolnikov, ki so dosegli odziv ACR 20.
At week 52 the co-primary endpoints were prevention of joint damage and improvement in physical function.
Po 52 tednih sta bili soprimarni končni točki preprečitev okvare sklepov in izboljšanje funkcionalne zmogljivosti.
Doses of 4 or 8 mg/ kg tocilizumab or placebo were given every four weeks, in combination with stable MTX (10 mg to 25 mg weekly).
Odmerke 4 ali 8 mg/ kg tocilizumaba ali placebo so dobivali na štiri tedne v kombinaciji s stabilnim odmerkom metotreksata (od 10 do 25 mg na teden).
Doses of 8 mg/ kg tocilizumab or placebo were given every four weeks in combination with stable DMARDs.
Odmerke 8 mg/ kg tocilizumaba ali placebo so dobivali na štiri tedne v kombinaciji s stabilnimi odmerki imunomodulirajočih antirevmatičnih zdravil.
Doses of 4 or 8 mg/ kg tocilizumab or placebo were given every four weeks in combination with stable MTX (10 mg to 25 mg weekly).
Odmerke 4 ali 8 mg/ kg tocilizumaba ali placebo so dobivali na štiri tedne v kombinaciji s stabilnim odmerkom metotreksata (od 10 do 25 mg na teden).
Clinical response In all studies, patients treated with tocilizumab 8 mg/ kg had statistically significant higher ACR 20, 50, 70 response rates at 6 months compared to control (Table 2).
Klinični odziv V vseh študijah so bili deleži odzivov ACR 20, 50 in 70 po 6 mesecih statistično značilno večji med bolniki, ki so dobivali 8 mg/ kg tocilizumaba kot med bolniki v kontrolnih skupinah (preglednica 2).
In study I, superiority of tocilizumab 8 mg/ kg was demonstrated against the active comparator MTX.
V študiji I so dokazali superiornost 8 mg/ kg tocilizumaba nad primerjalno učinkovino metotreksatom.
Continued durable responses were seen for over 24 months in the ongoing open label extension studies I, III, IV and V.
Neprekinjene trajne odzive prek 24 mesecev so opazili v odprtih podaljšanih študijah I, III, IV in V, ki še potekajo.
In patients treated with tocilizumab 8 mg/ kg, significant improvements were noted on all individual components of the ACR response including: tender and swollen joint counts; patients and physician global assessment; disability index scores; pain assessment and CRP compared to patients receiving placebo plus MTX or other DMARDs in all studies.
V vseh študijah so med zdravljenjem z 8 mg/ kg tocilizumaba v primerjavi z uporabo placeba v kombinaciji z metotreksatom ali drugimi imunomodulirajočimi antirevmatičnimi zdravili zabeležili
Patients in studies I – V had a mean Disease Activity Score (DAS28) of 6.5 – 6.8 at baseline.
10 značilno izboljšanje vseh posameznih elementov odziva ACR, vključno s številom bolečih in oteklih sklepov, bolnikovo in zdravnikovo oceno bolezni, kazalci preostalih sposobnosti, oceno bolečine in CRP.
Significant reduction in DAS28 from baseline (mean improvement) of 3.1– 3.4 were observed in tocilizumab-treated patients compared to control patients (1.3-2.1).
Bolniki v študijah I– V so imeli povprečno izhodiščno oceno aktivnosti bolezni DAS28 (Disease Activity Score) od 6, 5 do 6, 8.
The proportion of patients achieving a DAS28 clinical remission (DAS28 < 2.6) was significantly higher in patients receiving
Pri bolnikih, zdravljenih s tocilizumabom, so ugotovili značilno znižanje (povprečno izboljšanje) DAS28 za 3, 1 do 3, 4 od izhodišča v primerjavi s kontrolnimi bolniki (1, 3 do 2, 1).
10 tocilizumab (28 – 34%) compared to 1– 12% of control patients at 24 weeks.
Delež bolnikov, ki so dosegli klinično remisijo glede na DAS28 (DAS28 < 2, 6), je bil po 24 tednih značilno večji med bolniki, ki so dobivali tocilizumab (28– 34%), kot med kontrolnimi bolniki (1– 12%).
In study II, 47% of patients achieved a DAS28 < 2.6 at 52 weeks compared to 33% of patients at week 24.
V študiji II je po 52 tednih doseglo DAS28 < 2, 6 47% bolnikov v primerjavi s 33% bolnikov po 24 tednih.
In a pooled analysis of studies II, III and IV, the proportion of patients achieving an ACR 20, 50 and 70 response was significantly higher (59% vs.
V kumulativni analizi študij II, III in IV je bil delež bolnikov, ki so dosegli odziv ACR 20, 50 in 70, značilno večji med prejemniki 8 mg/ kg tocilizumaba skupaj z imunomodulirajočimi antirevmatičnimi zdravili kot med prejemniki 4 mg/ kg tocilizumaba skupaj z imunomodulirajočimi antirevmatičnimi zdravili (ACR 20:
50%, 37% vs.
59% v prim. s 50%, ACR 50:
27%, 18% vs.
37% v prim. s 27%, ACR 70:
11%, respectively) in the tocilizumab 8 mg/ kg plus DMARD vs. the tocilizumab 4 mg/ kg plus DMARD group (p < 0.03).
18% v prim. z 11%; p < 0, 03).
16% respectively) in patients receiving tocilizumab 8 mg/ kg plus DMARD than in patients receiving tocilizumab 4 mg/ kg plus DMARD (p < 0.0001).
Podobno je dosegel remisijo glede na DAS28 (DAS28 < 2, 6) značilno večji delež bolnikov, ki so dobivali 8 mg/ kg tocilizumaba skupaj z imunomodulirajočimi antirevmatičnimi zdravili, kot bolnikov, ki so dobivali 4 mg/ kg tocilizumaba skupaj z imunomodulirajočimi antirevmatičnimi zdravili (31% v prim. s 16%; p < 0, 0001).
ACR responses in placebo-/ MTX-/ DMARDs-controlled studies (% patients)
Odzivi ACR v študijah, kontroliranih s placebom/ metotreksatom/ imunomodulirajočimi antirevmatičnimi zdravili (% bolnikov).
Study IV
Študija IV
Study V
Študija V
Week
teden
MTX TCZ PBO TCZ PBO TCZ PBO + TCZ
MTX
TCZ MTX TCZ
TCZ
PBO TCZ PBO TCZ
placebo TCZ placebo
PBO TCZ PBO TCZ
placebo
TCZ MTX TCZ PBO TCZ PBO TCZ
TCZ
PBO +
placebo
8 +
8 mg/ kg + MTX
mg/ kg + MTX MTX
+
8 mg/ kg + MTX + MTX
MTX 8 mg/ kg + MTX + MTX
8 mg/ kg DMARD + DMARD
8 mg/ kg + DMARD
mg/ kg MTX
mg/ kg + MTX
N= 286
n= 286
N= 284
n= 284
N= 398
n= 398
N= N= N= 393 205 204 ACR 20
n= n= n= 393 205 204 ACR 20
N= 803
n= 803
N= 413
n= 413
N= 170
n= 170
N= 158
n= 158
52
MTX - metotreksat TCZ - tocilizumab DMARD * ** ***
PBO + MTX/ DMARD
- imunomodulirajoče antirevmatično zdravilo (Disease modifying anti- rheumatic drug) - p < 0, 05, tocilizumab v primerjavi s placebom + metotreksatom/ imunomodulirajočim antirevmatičnim zdravilom - p < 0, 01, tocilizumab v primerjavi s placebom + metotreksatom/ imunomodulirajočim antirevmatičnim zdravilom - p < 0, 0001, tocilizumab v primerjavi s placebom + metotreksatom/ imunomodulirajočim antirevmatičnim zdravilom
Radiographic response In Study II, in patients with an inadequate response to MTX, inhibition of structural joint damage was assessed radiographically and expressed as change in modified Sharp score and its components, the erosion score and joint space narrowing score.
Okvaro so izrazili kot spremembo ocene po modificiranem Sharpu in njenih elementov: ocene erozij in ocene zožitve sklepne špranje.
Inhibition of joint structural damage was shown with significantly less radiographic progression in patients receiving tocilizumab compared to control (Table 3).
Pri bolnikih, ki so dobivali tocilizumab so potrdili zavrtje strukturne okvare sklepov, saj je bilo na rentgenskih posnetkih značilno manj znakov napredovanja bolezni kot pri bolnikih v kontrolni skupini (preglednica 3).
11 Table 3.
11 Preglednica 3.
PBO + MTX
(+
= 393 1.13 0.71
Placebo + MTX TCZ od 24. tedna) n = 393
= 398 0.29* 0.17*
TCZ 8 mg/ kg + MTX n = 398
- Placebo - Methotrexate - Tocilizumab - Joint space narrowing
Celotna ocena Sharp- Genant Ocena erozij Ocena zožitve sklepne špranje MTX - metotreksat TCZ - tocilizumab
0.12**
1, 13 0, 71 0, 42
- p≤ 0.0001, TCZ vs.
0, 29 * 0, 17 * 0, 12 **
PBO + MTX
* - p ≤ 0, 0001, tocilizumab v primerjavi s placebom + metotreksatom ** - p < 0, 005, tocilizumab v primerjavi s placebom + metotreksatom
Health-related and quality of life outcomes Tocilizumab-treated patients reported an improvement in all patient-reported outcomes (Health Assessment Questionnaire Disability Index - HAQ-DI), Short Form-36 and Functional Assessment of Chronic Illness Therapy questionnaires.
Izidi, povezani s splošnim zdravstvenim stanjem in kakovostjo življenja S tocilizumabom zdravljeni bolniki so dosegli izboljšanje vseh izidov po navedbi bolnikov: vprašalniki HAQ- DI (Health Assessment Questionaire- Disability Index), SF- 36 (Short Form- 36) in FACIT (Functional Assessment of Chronic Illness Therapy).
Statistically significant improvements in HAQ-DI scores were observed in patients treated with RoActemra compared with patients treated with DMARDs.
Pri bolnikih, zdravljenih z zdravilom RoActemra, so v primerjavi s tistimi, ki so dobivali imunomodulirajoča zdravila, ugotovili statistično značilno izboljšanje ocen po HAQ- DI.
Haemoglobin levels Statistically significant improvements in haemoglobin levels were observed with tocilizumab compared with DMARDs (p < 0.0001) at week 24.
Koncentracija hemoglobina Po 24 tednih so pri tocilizumabu v primerjavi z imunomodulirajočimi antirevmatičnimi zdravili ugotovili statistično značilno izboljšanje koncentracije hemoglobina (p < 0, 0001).
Mean haemoglobin levels increased by week 2 and remained within normal range through to week 24.
5. 2 Farmakokinetične lastnosti
The pharmacokinetics of tocilizumab were determined using a population pharmacokinetic analysis on a database composed of 1,793 RA patients treated with a one-hour infusion of 4 and 8 mg/ kg tocilizumab every 4 weeks for 24 weeks.
Farmakokinetiko tocilizumaba so proučili s populacijsko farmakokinetično analizo podatkov 1793 bolnikov z revmatoidnim artritisom, ki so 24 tednov na 4 tedne dobivali enourno infuzijo 4 in 8 mg/ kg tocilizumaba.
The following parameters (predicted mean ± SD) were estimated for a dose of 8 mg/ kg tocilizumab given every 4 weeks: steady-state area under curve (AUC) = 35000 ± 15500 h µg/ ml, trough concentration (Cmin) = 9.74 ± 10.5 μ g/ ml and maximum concentration (Cmax) = 183 ± 85.6 µg/ ml, and. the accumulation ratios for AUC and Cmax were small, 1.22 and 1.06, respectively.
Za tocilizumab, uporabljen v odmerku 8 mg/ kg vsake 4 tedne, so bili ocenjeni naslednji parametri (napovedano povprečje ± standardni odklon): površina pod krivuljo (AUC) v stanju dinamičnega ravnovesja = 35. 000 ± 15. 500 h µg/ ml, najmanjša koncentracija (Cmin) = 9, 74 ± 10, 5 μg/ ml in največja koncentracija (Cmax) = 183 ± 85, 6 µg/ ml; deleža kopičenja sta bila majhna (1, 22 za AUC in 1, 06 za Cmax).
The accumulation ratio was higher for Cmin (2.35), which was expected based on the non-linear clearance contribution at lower concentrations.
Delež je bil večji za Cmin (2, 35), kar je pričakovano glede na nelinearen prispevek očistka pri nižjih koncentracijah.
Distribution In RA patients the central volume of distribution was 3.5 l, the peripheral volume of distribution was 2.9 l resulting in a volume of distribution at steady state of 6.4 l.
Porazdelitev Pri bolnikih z revmatoidnim artritisom je bil centralni volumen porazdelitve 3, 5 l in periferni volumen porazdelitve 2, 9 l, tako da je volumen porazdelitve v stanju dinamičnega ravnovesja 6, 4 l.
Elimination Following intravenous administration, tocilizumab undergoes biphasic elimination from the circulation.
Izločanje Po intravenski uporabi se tocilizumab iz obtoka odstrani v dveh fazah.
The linear clearance was estimated as a parameter in the population pharmacokinetic analysis and was 12.5 ml/ h.
Linearni očistek so ocenili kot parameter v analizi populacijske farmakokinetike, znašal je 12, 5 ml/ h.
The t1/ 2 of tocilizumab was concentration-dependent.
Razpolovni čas (t1/ 2) tocilizumaba je odvisen od koncentracije.
At steady-state following a dose of 8 mg/ kg every 4 weeks, the effective t1/ 2 decreased with decreasing concentrations within a dosing interval from 14 days to 8 days.
V stanju dinamičnega ravnovesja po odmerku 8 mg/ kg na 4 tedne se je efektivni t1/ 2 skrajševal z zniževanjem koncentracij v odmernem intervalu od 14 dni do 8 dni.
12 dose-proportionally.
12 Linearnost Farmakokinetični parametri tocilizumaba se s časom niso spreminjali.
At steady-state, predicted AUC and Cmin were 2.7 and 6.5 fold higher at 8 mg/ kg as compared to 4 mg/ kg, respectively.
V stanju dinamičnega ravnovesja je bila AUC po odmerku 8 mg/ kg 2, 7- krat večja, Cmin pa 6, 5- krat večja kot po odmerku 4 mg/ kg.
No formal study of the effect of renal impairment on the pharmacokinetics of tocilizumab has been conducted.
Posebne populacije Okvara ledvic: formalnih študij o vplivu okvare ledvic na farmakokinetiko tocilizumaba niso izvedli.
Mild renal impairment (creatinine clearance based on Cockcroft-Gault < 80 ml/ min and ≥ 50 ml/ min) did not impact the pharmacokinetics of tocilizumab.
Blaga okvara ledvic (očistek kreatinina po Cockcroft- Gaultovi formuli < 80 ml/ min in ≥ 50 ml/ min) ni vplivala na farmakokinetiko tocilizumaba.
No formal study of the effect of hepatic impairment on the pharmacokinetics of tocilizumab has been conducted.
Okvara jeter: formalnih študij o vplivu okvare jeter na farmakokinetiko tocilizumaba niso izvedli.
Population pharmacokinetic analyses in adult RA patients, showed that age, gender and ethnic origin did not affect the pharmacokinetics of tocilizumab.
Starost, spol in etnična pripadnost: analize populacijske farmakokinetike pri odraslih bolnikih z revmatoidnim artritisom so pokazale, da starost, spol in etnična pripadnost ne vplivajo na farmakokinetiko tocilizumaba.