natgillin/translations-raw huggingface dataset:
En fuldstændig blodtælling skal foretages på dag 22 (21 dage efter den første dosis) eller inden for 48 timer herefter, og ugentligt indtil ANC > 1, 5 x 109/ l og trombocyttallet > 100 x 109/ l.
A complete blood count should be obtained on Day 22 (21 days after the first dose) or within 48 hours of that day, and weekly until ANC > 1.5 x 109/l and platelet count > 100 x 109/l.
4. 2).
If ANC falls to < 1.0 x 109/l or the platelet count is < 50 x 109/l during any cycle, the next cycle should be reduced one dose level (see section 4.2).
Dosisniveauerne omfatter 100 mg/ m2, 150 mg/ m2 og 200 mg/ m2.
Dose levels include 100 mg/m2, 150 mg/m2, and 200 mg/m2.
Den lavest anbefalede dosis er 100 mg/ m2.
The lowest recommended dose is 100 mg/m2.
4. 2 og 5. 1).
Experience in older children and adolescents is very limited (see sections 4.2 and 5.1).
Mænd, der behandles med TMZ, frarådes at gøre nogen gravid i op til 6 måneder efter at have modtaget den sidste dosis.
Men being treated with TMZ should be advised not to father a child up to 6 months after receiving the last dose and to seek advice on cryoconservation of sperm prior to treatment (see section 4.6).
4. 6).
Lactose
Lactose Dette lægemiddel indeholder lactose.
This medicinal product contains lactose.
Patienter med sjældne arvelige sygdomme med galaktose intolerance, total laktase- mangel eller glukose- galaktose- malabsorption bør derfor ikke anvende dette lægemiddel.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
5 I et separat fase I- studie resulterede indtagelse af TMZ sammen med ranitidin ikke i ændringer i absorptionsgraden af temozolomid eller eksponeringen over for dets aktive metabolit monomethyltriazenoimidazolcarboxamid (MTIC).
5 In a separate phase I study, administration of TMZ with ranitidine did not result in alterations in the extent of absorption of temozolomide or the exposure to its active metabolite monomethyl triazenoimidazole carboxamide (MTIC).
Indtagelse af TMZ med føde resulterede i et 33% fald i Cmax og et 9% fald i arealet under kurven (AUC).
Administration of TMZ with food resulted in a 33% decrease in Cmax and a 9% decrease in area under the curve (AUC).
På basis af en analyse af populationsfarmakokinetik i fase II- undersøgelser, ændrede samtidig anvendelse af dexamethason, prochlorperazin, phenytoin, carbamazepin, ondansetron, H2- receptor - antagonister eller phenobarbital ikke udskillelsen af TMZ.
Based on an analysis of population pharmacokinetics in phase II trials, co-administration of dexamethasone, prochlorperazine, phenytoin, carbamazepine, ondansetron, H2 receptor antagonists, or phenobarbital did not alter the clearance of TMZ.
Samtidig indtagelse af valproat var forbundet med et lille, men statistisk signifikant fald i TMZ- clearance.
Co-administration with valproic acid was associated with a small but statistically significant decrease in clearance of TMZ.
Ingen undersøgelser er udført for at bestemme TMZ’ s effekt på metabolisering eller elimination af andre lægemidler.
No studies have been conducted to determine the effect of TMZ on the metabolism or elimination of other medicinal products.
5. 2).
However, since TMZ does not undergo hepatic metabolism and exhibits low protein binding, it is unlikely that it would affect the pharmacokinetics of other medicinal products (see section 5.2).
Graviditet Der foreligger ingen data om anvendelse til gravide.
There are no data in pregnant women.
I prækliniske undersøgelser udført på rotter og kaniner med doser på 150 mg/ m2 TMZ blev teratogenicitet og/ eller føtal toksicitet påvist (se pkt.
In preclinical studies in rats and rabbits receiving 150 mg/m2 TMZ, teratogenicity and/or foetal toxicity were demonstrated (see section 5.3).
Temodal hårde kapsler bør ikke anvendes til gravide kvinder.
Temodal hard capsules should not be administered to pregnant women.
Kvinder i den fertile alder skal anbefales at anvende sikker krontraception for at undgå graviditet under behandling med TMZ.
Women of childbearing potential should be advised to use effective contraception to avoid pregnancy while they are receiving TMZ.
Evnen til at køre eller betjene maskiner kan være forringet hos patienter behandlet med TMZ på grund af træthed og søvnighed.
The ability to drive and use machines may be impaired in patients treated with TMZ due to fatigue and somnolence.
Hos de nyligt diagnosticerede patienter med glioblastom multiforme, der modtog monoterapi, blev kramper
Convulsions were reported very commonly in the newly- diagnosed glioblastoma multiforme patients receiving monotherapy, and rash was reported very
Hos patienter med tilbagevendende gliom blev udslæt rapporteret som værende almindeligt.
6 commonly in newly-diagnosed glioblastoma multiforme patients receiving TMZ concurrent with RT and also as monotherapy, and commonly in recurrent glioma.
De fleste hæmatologiske bivirkninger blev rapporteret som værende almindelige eller meget almindelige for begge indikationer (Tabel 4 og 5); hyppighed af grad 3- 4 laboratoriefund er angivet efter hver tabel.
Most haematologic adverse reactions were reported commonly or very commonly in both indications (Tables 4 and 5);the frequency of grade 3-4 laboratory findings is presented after each table.
Hyppigheden er defineret i henhold til følgende konvention:
Frequency groupings are defined according to the following convention:
Meget almindelig (≥ 1/ 10); almindelig (≥ 1/ 100 til < 1/ 10); ikke almindelig (≥ 1/ 1. 000 til < 1/ 100).
Very common (≥ 1/10); Common (≥ 1/100 to < 1/10); Uncommon (≥ 1/1,000 to < 1/100).
Tabel 4 anfører bivirkninger fremkommet hos patienter med nydiagnosticeret glioblastoma multiforme under konkomitant - og monoterapi behandlingsfaserne.
Table 4 provides treatment-emergent adverse events in patients with newly-diagnosed glioblastoma multiforme during the concomitant and monotherapy phases of treatment.
Bivirkninger fremkommet hos patienter med ny diagnosticeret glioblastoma multiforme under konkomitant - og monoterapi- behandlingsfaserne Systemorganklasse
Treatment-emergent events during concomitant and monotherapy treatment phases in patients with newly-diagnosed glioblastoma multiforme
TMZ + konkomitant strålebehandling n=288 *
System Organ Class Infections and infestations
TMZ monoterapi n=224
concomitant RT n=288*
Infektioner og parasitære sygdomme
monotherapy n=224
Herpes simplex, Herpes zoster, influenzalignende symptomer
Herpes simplex, herpes zoster, influenza–like symptoms
Almindelige:
Blood and lymphatic system disorders Common:
Febril neutropeni, thrombocytopeni, anæmi, leukopeni
Febril neutropenia, thrombocytopenia, anaemia, leukopenia
Anoreksi Vægttab
Uncommon:
Psykiske forstyrrelser
Anorexia Hyperglycaemia, weight decreased Hypokalemia, alkaline phosphatase increased, weight increased
Hypokalæmi, forhøjet alkalisk fosfatase, vægtøgning
Anorexia Weight decreased Hyperglycaemia, weight increased
Hyperglycæmi, vægtøgning
Psychiatric disorders
Meget almindelige:
Nervous system disorders Very common:
7 Almindelige:
7 Common:
Almindelige:
Ear and labyrinth disorders Common:
Ikke almindelig:
Cardiac disorders Uncommon:
Meget almindelige:
Gastrointestinal disorders Very common:
Meget almindelige:
8 Very common:
Dermatitis, tør hud, erythem, kløe Hudeksfoliering,
Dermatitis, dry skin, erythema, pruritus
Tør hud, kløe Erythem, unormal pigmentering, øget
Dry skin, pruritus
8
Uncommon:
lysoverfølsomhedsreaktion, unormal pigmentering
Skin exfoliation, photosensitivity reaction, pigmentation abnormal
Knogler, led, muskler og bindevæv
Erythema, pigmentation abnormal, sweating increased
Almindelige:
Musculoskeletal and connective tissue disorders Common:
Almindelige:
Renal and urinary disorders Common:
Det reproduktive system og mammae
Reproductive system and breast disorders Uncommon:
Almene symptomer og reaktioner på administrationsstedet
General disorders and administration site conditions Very common:
Meget almindelig:
Fatigue
Træthed Allergisk reaktion, feber, stråleskade, ansigtsødem, smerte, smagsforstyrrelse
Allergic reaction, fever, radiation injury, face oedema, pain, taste perversion
Træthed Allergisk reaktion, feber, stråleskade, smerte, smagsforstyrrelse
Allergic reaction, fever, radiation injury, pain, taste perversion
Asteni, ansigtsødem, smerte, forværret tilstand, rigor, tandlidelse, smagsforstyrrelse
Asthenia, face oedema, pain, condition aggravated, rigors, tooth disorder, taste perversion
Almindelig:
Investigations
* En patient, der kun var randomiseret til strålebehandlingsgruppen, fik TMZ + strålebehandling.
*A patient who was randomised to the RT arm only, received TMZ + RT.
Når unormale laboratorieværdier og bivirkninger blev slået sammen på tværs af konkomitante og monoterapi- behandlingsfaser, blev Grad 3 - eller Grad 4- neutrofilabnormaliteter inklusive neutropeni- bivirkninger set hos 8% af patienterne.
When laboratory abnormalities and adverse events were combined across concomitant and monotherapy treatment phases, Grade 3 or Grade 4 neutrophil abnormalities including neutropenic events were observed in 8% of the patients.
Grad - 3 eller Grad 4- trombocytabnormaliteter, inklusive trombocytopeni- bivirkninger blev set hos 14% af patienterne, der fik TMZ.
Grade 3 or Grade 4 thrombocyte abnormalities, including thrombocytopenic events were observed in 14% of the patients who received TMZ.
I kliniske forsøg var de hyppigst forekommende behandlingsrelaterede bivirkninger gastrointestinale forstyrrelser, særligt kvalme (43%) og opkastninger (36%).
These reactions were usually
Disse bivirkninger var oftest grad 1 eller 2, (0- 5 opkastninger inden for 24 timer) og ophørte af sig selv eller kunne let kontrolleres med kvalmestillende standard- behandling.
9 Grade 1 or 2 (0 – 5 episodes of vomiting in 24 hours) and were either self-limiting or readily controlled with standard anti-emetic therapy.
Hyppigheden af alvorlig kvalme og opkastning var 4%.
The incidence of severe nausea and vomiting was 4%.
Neutropeni eller lymfopeni (grad 3- 4), trombocytopeni (grad 3- 4)
Neutropenia or lymphopenia (grade 3-4), thrombocytopenia (grade 3-4)
Pancytopeni, anæmi (grad 3- 4), leukopeni
Pancytopenia, anaemia (grade 3-4), leukopenia
Anoreksi Vægttab
Anorexia Weight decrease
Luftveje, thorax og mediastinum
Headache Somnolence, dizziness, paresthesia
Hovedpine Søvnighed, svimmelhed, parestesier
Respiratory, thoracic and mediastinal disorders
Opkastning, kvalme, forstoppelse Diarré, mavesmerte, dyspepsi
Vomiting, nausea, constipation Diarrhoea, abdominal pain, dyspepsia
Udslæt, kløe, alopeci Erythema multiforme, erythroderma, urticaria, exantem
Rash, pruritus, alopecia Erythema multiforme, erythroderma, urticaria, exanthema
Allergiske reaktioner, inklusive anafylaksi, angioødem
Fatigue Fever, asthenia, rigors, malaise, pain, taste perversion Allergic reactions, including anaphylaxis, angioedema
Grad 3 - eller 4- trombocytopeni og neutropeni forekom hos henholdsvis 19% og 17% af patienterne behandlet for malignt gliom.
Grade 3 or 4 thrombocytopenia and neutropenia occurred in 19% and 17% respectively, of patients treated for malignant glioma.
Dette medførte hospitalisering og/ eller seponering af TMZ hos henholdsvis 8% and 4% af patienter med gliom.
This led to hospitalisation and/or discontinuation of TMZ in 8% and 4%, respectively.
Myelosuppression var forudsigelig (sædvanligvis inden for de første få serie med nadir mellem dag 21 og dag 28), og bedring indtraf hurtigt, sædvanligvis inden for 1- 2 uger.
Myelosuppression was predictable (usually within the first few cycles, with the nadir between Day 21 and Day 28), and recovery was rapid, usually within 1-2 weeks.
5%, og thrombocytopeni (< 20 x 109/ l), 9% vs.
There were higher rates of Grade 4 neutropenia (ANC < 0.5 x 109/l), 12% vs 5%, and thrombocytopenia (< 20 x 109/l), 9% vs 3%, in women vs men in the first cycle of therapy.
I et gentaget glioma datasæt med 400 forsøgspersoner forekom Grad 4- neutropeni hos 8% af de kvindelige vs.
In a 400 subject recurrent glioma data set, Grade 4 neutropenia occurred in 8% of female vs 4% of male subjects and Grade 4 thrombocytopenia in 8% of female vs 3% of male
3% af de mandlige forsøgspersoner i det første terapiforløb.
10 subjects in the first cycle of therapy.
0% af de mandlige forsøgspersoner og Grad 4- thrombocytopeni hos 1% af de kvindelige vs.
In a study of 288 subjects with newly-diagnosed glioblastoma multiforme, Grade 4 neutropenia occurred in 3% of female vs 0% of male subjects and Grade 4 thrombocytopenia in 1% of female vs 0% of male subjects in the first cycle of therapy.
10 Erfaring efter markedsføring:
Post-Marketing Experience
Antineoplastiske midler, og især alkylerende midler, har været forbundet med en mulig risiko for myelodysplastisk syndrom (MDS) og sekundære maligne lidelser, inklusive leukæmi.
Antineoplastic agents, and notably alkylating agents, have been associated with a potential risk of myelodysplastic syndrome (MDS) and secondary malignancies, including leukaemia.
Meget sjældne tilfælde af MDS og sekundære maligne lidelser, inklusive myeloid leukæmi er blevet rapporteret hos patienter behandlet med et regime, som inkluderede TMZ.
Very rare cases of MDS and secondary malignancies, including myeloid leukaemia have been reported in patients treated with regimens that included TMZ.
Længerevarende pancytopeni, som kan medføre aplastisk anæmi, er blevet rapporteret meget sjældent.
Prolonged pancytopenia, which may result in aplastic anaemia has been reported very rarely.
Der har meget sjældent været rapporteret tilfælde af toksisk epidermal nekrolyse og Stevens- Johnson syndrom.
Cases of toxic epidermal necrolysis and Stevens-Johnson syndrome have been reported very rarely.
Der er meget sjældent set tilfælde af interstitiel pneumonitis/ pneumonitis.
Cases of interstitial pneumonitis/pneumonitis have been reported very rarely.
Doser på 500, 750, 1. 000 og 1. 250 mg/ m2 (total dosis pr serie over 5 dage) er blevet vurderet klinisk hos patienter.
Doses of 500, 750, 1,000, and 1,250 mg/m2 (total dose per cycle over 5 days) have been evaluated clinically in patients.
Én patient har taget en overdosis på 10. 000 mg (total dosis i en enkelt serie over 5 dage), og de rapporterede bivirkninger var pancytopeni, pyreksi, multiorgansvigt og dødsfald.
An overdose of 10,000 mg (total dose in a single cycle, over 5 days) was taken by one patient and the adverse reactions reported were pancytopenia, pyrexia, multi- organ failure and death.
Antineoplastiske midler - Andre alkylerende midler, ATC- kode:
Antineoplastic agents - Other alkylating agents, ATC code:
L01A X03.
L01A X03
MTIC’ s cytotoksiske effekt formodes primært at skyldes alkyleringen ved O6- positionen i guanin med ledsagende alkylering ved N7- positionen.
The cytotoxicity of MTIC is thought to be due primarily to alkylation at the O6 position of guanine with additional alkylation also occurring at the N7 position.
Cytotoksiske læsioner, der udvikles efterfølgende, synes at involvere aberrant reparation af methyl - adduktet.
Cytotoxic lesions that develop subsequently are thought to involve aberrant repair of the methyl adduct.
Patienter, der var i den gruppe, der modtog TMZ + strålebehandling, fik konkomitant TMZ (75 mg/ m2) én gang dagligt, begyndende den første strålebehandlingsdag indtil den sidste strålebehandlingsdag, i 42 dage (med højst 49 dage).
Patients in the TMZ + RT arm received concomitant TMZ (75 mg/m2) once daily, starting the first day of RT until the last day of RT, for 42 days (with a maximum of 49 days).
Dette blev efterfulgt af monoterapi med TMZ (150 - 200 mg/ m2) på dag 1 - 5 i hver 28- dags- serie i op til 6 serier, startende 4 uger efter afsluttet strålebehandling.
This was followed by monotherapy TMZ (150 - 200 mg/m2) on Days 1 - 5 of every 28-day cycle for up to 6 cycles, starting 4 weeks after the end of RT.
Pneumocystis carinii pneumoni (PCP) forebyggende behandling var påkrævet under strålebehandling og konkomitant TMZ behandling.
Pneumocystis carinii pneumonia (PCP) prophylaxis was required during RT and combined TMZ therapy.
TMZ blev givet som salvage- behandling i opfølgningsfasen hos 161 patienter af 282 (57%) i armen med strålebehandling alene, og 62 patienter af 277 (22%) i armen med TMZ + strålebehandling.
TMZ was administered as salvage therapy in the follow-up phase in 161 patients of the 282 (57%) in the RT alone arm, and 62 patients of the 277 (22%) in the TMZ + RT arm.
Risiko forholdene (HR) for den totale overlevelse var 1, 59 (95% CI for HR=1, 33 - 1, 91) med en log - rank p < 0, 0001 til fordel for TMZ- gruppen.
11 The hazard ratio (HR) for overall survival was 1.59 (95% CI for HR=1.33 -1.91) with a log-rank p < 0.0001 in favour of the TMZ arm.
10%) er højere for gruppen med strålebehandling + TMZ.
The estimated probability of surviving 2 years or more (26% vs 10%) is higher for the RT + TMZ arm.
Supplement med konkomitant TMZ til strålebehandling, efterfulgt af TMZ monoterapi i behandlingen af patienter med
The addition of concomitant TMZ to RT, followed by TMZ monotherapy in the treatment of patients with newly-diagnosed glioblastoma multiforme demonstrated a statistically significant improvement in overall survival (OS) compared with RT alone (Figure 1).
Total overlevelse
H R (9 5% C .I.) = 1 .5 9 (1 .3 3 – 1 .9 1) lo g -ra n k p -va lu e < .0 0 0 1
Sandsynlighed
26% RT+TM Z
– 1, 91)
10% R T O n ly
12, 1
1 2 .1
14, 6
1 4 .6
Kaplan- Meier- kurver for total overlevelse (intent- to- treat population)
Kaplan-Meier curves for overall survival (intent-to-treat population)
Den ene var en ikke- sammenlignende undersøgelse hos 138 patienter (29% fik tidligere kemoterapi), og den anden var en randomiseret aktiv- kontrolleret undersøgelse med TMZ versus procarbazin hos i alt 225 patienter (67% fik tidligere behandling med nitrosurea baseret kemoterapi).
One was a non-comparative trial in 138 patients (29% received prior chemotherapy), and the other was a randomised active-controlled trial of TMZ vs procarbazine in a total of 225 patients (67% received prior treatment with nitrosourea based chemotherapy).
I begge undersøgelser var det primære grænsepunkt progressionsfri overlevelse (PFS) defineret ved MRI- scanning eller neurologisk forværring.
In both trials, the primary endpoint was progression-free survival (PFS) defined by MRI scans or neurological worsening.
I den ikke- randomiserede undersøgelse var PFS efter 6 måneder 19%, median progressiv overlevelse var 2, 1 måneder, og median samlet overlevelse 5, 4 måneder.
In the non- comparative trial, the PFS at 6 months was 19%, the median progression-free survival was 2.1 months, and the median overall survival 5.4 months.
Den objektive responsrate (ORR) baseret på MRI scanninger var 8%.
The objective response rate (ORR) based on MRI scans was 8%.
I den randomiserede aktive kontrollerede undersøgelse var 6 måneders PFS signifikant større for TMZ end for procarbazin (henholdsvis 21% versus 8% - chi- square p = 0, 008) med median PFS på henholdsvis 2, 89 og 1, 88 måneder (log rank p = 0, 33).
In the randomised active-controlled trial, the PFS at 6 months was significantly greater for TMZ than for procarbazine (21% vs 8%, respectively – chi-square p = 0.008) with median PFS of 2.89 and 1.88 months respectively (log rank p = 0.0063).
Den mediane overlevelse var 7, 34 og 5, 66 måneder for henholdsvis TMZ og procarbazin (log rank p = 0, 33).
The median survival was 7.34 and 5.66 months for TMZ and procarbazine, respectively (log rank p = 0.33).
Efter 6 måneder var andelen af overlevende patienter signifikant større i TMZ- gruppen (60%) sammenlignet med procarbazin - gruppen (44%) (chi- square p = 0, 019).
At 6 months, the fraction of surviving patients was significantly higher in the TMZ arm (60%) compared with the procarbazine arm (44%) (chi-square p = 0.019).
Median- tiden til progression af disse endpoints varierede fra at være 0, 7 til 2, 1 måneder længere for TMZ end for procarbazin (log rank p = < 0, 01 til 0, 03).
The median times to progression in these endpoints ranged from 0.7 to 2.1 months longer for TMZ than for procarbazine (log rank p = < 0.01 to 0.03).
Tilbagevendende anaplastisk astrocytoma
12 Recurrent anaplastic astrocytoma
I en multicenter, prospektiv fase II- undersøgelse, der vurderede sikkerhed og effekt af oral TMZ i behandlingen af patienter med anaplastisk astrocytoma ved første relaps, var 6 måneders PFS 46%.
In a multicentre, prospective phase II trial evaluating the safety and efficacy of oral TMZ in the treatment of patients with anaplastic astrocytoma at first relapse, the 6 month PFS was 46%.
Den mediane PFS var 5, 4 måneder.
The median PFS was 5.4 months.
Median samlet overlevelse var 14, 6 måneder.
Median overall survival was 14.6 months.
12 Responsrate, baseret på den centrale reviewers vurdering, var 35% (13 CR og 43 PR) for intent- to- treat populationen (ITT) n=162.
Response rate, based on the central reviewer assessment, was 35% (13 CR and 43 PR) for the intent-to-treat population (ITT) n=162.
Den 6- måneders hændelses- frie overlevelse for ITT populationen var 44% med en median event- fri overlevelse på 4, 6 måneder, hvilket var i lighed med resultaterne for den progressionsfri overlevelse.
The 6-month event-free survival for the ITT population was 44% with a median event-free survival of 4.6 months, which was similar to the results for the progression-free survival.
TMZ blev givet daglig i 5 dage hver 28. dag.
Oral TMZ has been studied in paediatric patients (age 3-18 years) with recurrent brainstem glioma or recurrent high grade astrocytoma, in a regimen administered daily for 5 days every 28 days.
TMZ hydrolyseres spontant ved fysiologisk pH primært til det aktive stof, 3- methyl - (triazen- 1 - yl) imidazol- 4- carboxamid (MTIC).
TMZ is spontaneously hydrolyzed at physiologic pH primarily to the active species, 3-methyl-(triazen- 1-yl)imidazole-4-carboxamide (MTIC).
MTIC hydrolyseres spontant til 5- amino- imidazol- 4- carboxamid (AIC), et kendt mellemprodukt i purin - og nucleinsyrebiosyntesen, og til methylhydrazin, som menes at være det aktive alkylerende stof.
MTIC is spontaneously hydrolyzed to 5-amino-imidazole-4- carboxamide (AIC), a known intermediate in purine and nucleic acid biosynthesis, and to methylhydrazine, which is believed to be the active alkylating species.
I forhold til AUC af TMZ er eksponeringen til MTIC og AIC henholdsvis ~ 2, 4% og 23%.
Relative to the AUC of TMZ, the exposure to MTIC and AIC is ~ 2.4% and 23%, respectively.
In vivo var t1/ 2 for MTIC 1, 8 timer som for TMZ.
In vivo, the t1/2 of MTIC was similar to that of TMZ, 1.8 hr.
Efter peroral administration til voksne absorberes TMZ hurtigt, og maksimalkoncentrationerne opnås allerede efter 20 minutter (gennemsnitstider mellem 0, 5 og 1, 5 time).
After oral administration to adult patients, TMZ is absorbed rapidely, with peak concentrations reached as early as 20 minutes post-administration (mean time between 0.5 and 1.5 hours).
Efter peroral administration af 14 C- mærket TMZ var den gennemsnitlige fækale udskillelse af 14C over 7 dage 0, 8%, hvilket tyder på fuldstændig absorption.
After oral administration of 14C-labelled TMZ, mean faecal excretion of 14C over 7 days post-dose was 0.8% indicationg complete absorption.
TMZ har en lav proteinbinding (10% til 20%) og forventes derfor ikke at interagere med stærkt proteinbundne stoffer.
TMZ demonstrates low protein binding (10% to 20%), and thus it is not expected to interact with highly protein-bound substances.
PET- undersøgelser hos mennesker samt prækliniske data tyder på, at TMZ hurtigt passerer blodhjernebarrieren og er til stede i CSF.
PET studies in humans and preclinical data suggest that TMZ crosses the blood-brain barrier rapidly and is present in the CSF.
CSF penetration blev bekræftet hos en patient; CSF - eksponering baseret på AUC for TMZ var cirka 30% i forhold til plasma, hvilket er konsistent med data fra dyr.
CSF penetration was confirmed in one patient; CSF exposure based on AUC of TMZ was approximately 30% of that in plasma, which is consistent with animal data.
1, 8 timer.
The half-life (t1/2) in plasma is approximately 1.8 hours.