natgillin/translations-raw huggingface dataset:
Påvisning af gavn er baseret på histologiske, virologiske, biokemiske og serologiske respons efter 48 ugers behandling i aktivt kontrollerede kliniske forsøg med 1. 633 voksne med kronisk hepatitis B infektion og dokumenteret virusreplikation.
Clinical experience: the demonstration of benefit is based on histological, virological, biochemical, and serological responses after 48 weeks of treatment in active-controlled clinical trials of 1,633 adults with chronic hepatitis B infection and evidence of viral replication.
I alle forsøg defineredes histologisk forbedring som et ≥ 2- point fald i Knodell nekro- inflammatorisk score fra baseline uden forværring i Knodell fibrose- scoren.
In all studies, histological improvement was defined as a ≥ 2-point decrease in Knodell necro- inflammatory score from baseline with no worsening of the Knodell fibrosis score.
Respons hos patienter med en Knodell fibrose- score på 4 (cirrhose) ved baseline var sammenlignelig med den overordnede respons på alle
Responses for patients with baseline Knodell Fibrosis Scores of 4 (cirrhosis) were comparable to overall responses on all efficacy outcome measures (all patients had compensated liver disease).
Høje baseline Knodell nekroinflammatoriske scorer (> 10) var forbundet med større histologisk forbedring hos patienter, der ikke tidligere havde været i nukleosidbehandling.
High baseline Knodell necroinflammatory scores (> 10) were associated with greater histological improvement in nucleoside- naive patients.
Såvel baseline ALAT- niveauer ≥ 2 x ULN som baseline HBV DNA ≤ 9, 0 log10 kopier/ ml var forbundet med højere forekomst af virologisk respons (Uge 48 HBV DNA < 400 kopier/ ml) hos HBeAg- positive patienter, der ikke tidligere var blevet behandlet med nukleosid.
Baseline ALT levels ≥ 2 x ULN and baseline HBV DNA ≤ 9.0 log10 copies/ ml were both associated with higher rates of virologic response (Week 48 HBV DNA < 400 copies/ ml) in nucleoside-naive HBeAg-positive patients.
Uafhængigt af baseline- karakteristikaviste de fleste patienter histologisk og virologisk respons på behandling.
Regardless of baseline characteristics, the majority of patients showed histological and virological responses to treatment.
Erfaring hos patienter med kompenseret leversygdom, der ikke tidligere har været i nukleosidbehandling:
Results at 48 weeks of randomised, double blind studies comparing entecavir (ETV) to lamivudine
Tabellen viser resultater efter 48 uger fra randomiserede, dobbeltblinde forsøg, der sammenligner entecavir (ETV) med lamivudin (LVD) hos HBeAg- positive (022) og HBeAg- negative (027) patienter.
8 (LVD) in HBeAg positive (022) and HBeAg negative (027) patients are presented in the table.
Ingen tidligere nukleosid- behandling
Nucleoside Naive
HBeAg- positiv (studie 022)
HBeAg Positive (study 022)
HBeAg- negativ (studie 027)
HBeAg Negative (study 027)
én gang
0.5 mg
100 mg én én gang
100 mg 0.5 mg
én gang 100 mg én én gang
0.5 mg 100 mg 0.5 mg
100 mg én
100 mg
gang daglig
once daily once daily once daily a a a
daglig
once daily
N Histologisk forbedringb Forbedring i Ishak fibrose- score Forværring i Ishak fibrose- score N Fald i viral load (log10 kopier/ ml) c HBV- DNA kan ikke påvises (< 300 kopier/ ml ved PCR) c
n Histological improvementb Ishak fibrosis score improvement Ishak fibrosis score worsening n Viral load reduction (log10 copies/ ml)c HBV DNA undetectable (< 300 copies/ ml by PCR)c
314a 62% 35% 10% 355 - 5, 39 36%
314 314 296 72%* 62% 70%* 39% 35% 36% 8% 10% 12% 354 355 325 -6.86* -5.39 -5.04* 67%* 36% 90%*
ALAT- normalisering (≤ 1 gang ULN)
ALT normalisation (≤ 1 times ULN)
HBeAg- serokonvertering * p- værdi vs lamivudin < 0, 05 a
HBeAg Seroconversion *p value vs lamivudine < 0.05 a
patienter med evaluérbar histologi ved baseline (baseline Knodell- nekroinflammatorisk score ≥ 2) b et primært endpoint c Roche Cobas Amplicor PCR- assay (LLOQ = 300 kopier/ ml)
patients with evaluable baseline histology (baseline Knodell Necroinflammatory Score ≥ 2) b a primary endpoint c Roche Cobas Amplicor PCR assay (LLOQ = 300 copies/ ml)
I et randomiseret, dobbeltblindt forsøg med HBeAg- positive, lamivudin- refraktoriske patienter (026), hvor 85% af patienterne havde LVDr - mutationer ved baseline, skiftede patienter, der fik lamivudin ved inklusion, til entecavir 1 mg, én gang dagligt, uden udvaskning eller overlap (n = 141) eller patienterne fortsatte med lamivudin 100 mg, én gang dagligt (n = 145).
In a randomised, double-blind study in HBeAg positive lamivudine-refractory patients (026), with 85% of patients presenting LVDr mutations at baseline, patients receiving lamivudine at study entry either switched to entecavir 1 mg once daily, with neither a washout nor an overlap period (n = 141), or continued on lamivudine 100 mg once daily (n = 145).
9 Lamivudin- refraktion HBeAg- positiv (studie 026)
Lamivudine-refractory HBeAg positive (study 026) ETV 1.0 mg once daily LVD 100 mg once daily n
LVD 100
124a
mg én gang daglig
116a
N Histologisk forbedringb Forbedring i Ishak fibrose- score Forværring i Ishak fibrose- score N Fald i viral load (log10 kopier/ ml) c HBV- DNA kan ikke påvises (< 300 kopier/ ml ved PCR) c
Histological improvementb Ishak fibrosis score improvement Ishak fibrosis score worsening n Viral load reduction (log10 copies/ ml)c HBV DNA undetectable (< 300 copies/ ml by PCR)c
124 55% * 34% * 11% 141 - 5, 11 * 19% *
55%* 34%* 11% 141 -5.11* 19%*
patienter med evaluérbar histologi ved baseline (baseline Knodell- nekroinflammatorisk score ≥ 2) b et primært endpoint c Roche Cobas Amplicor PCR- assay (LLOQ = 300 kopier/ ml)
patients with evaluable baseline histology (baseline Knodell Necroinflammatory Score ≥ 2) b a primary endpoint. c Roche Cobas Amplicor PCR assay (LLOQ = 300 copies/ ml)
Responskriterier var HBV- virologisk suppression (HBV DNA < 0, 7 MEq/ ml ved bDNA) og tab af HBeAg (hos HBeAg- positive patienter) eller ALAT < 1, 25 gange ULN (hos HBeAg- negative patienter).
Response criteria were HBV virological suppression (HBV DNA < 0.7 MEq/ ml by bDNA) and loss of HBeAg (in HBeAg positive patients) or ALT < 1.25 times ULN (in HBeAg negative patients).
Patienter der responderede blev fulgt i yderligere 24 uger efter seponering af behandling.
Patients in response were followed for an additional 24 weeks off-
HBeAg- positive (studie 022):
Nucleoside-naive:
Behandling med entecavir i op til 96 uger (n = 354) gav kumulative responsrater på 80% for HBV DNA < 300 kopier/ ml ved PCR, 87% for ALAT- normalisering, 31% for HBeAg- serokonvertering og 2% for HBsAg- serokonvertering (5% for HBsAg- tab).
HBeAg positive (study 022): treatment with entecavir for up to 96 weeks (n = 354) resulted in cumulative response rates of 80% for HBV DNA < 300 copies/ ml by PCR, 87% for ALT normalisation, 31% for HBeAg seroconversion and 2% for HBsAg seroconversion (5% for HBsAg loss).
For lamivudin (n = 355) var de kumulative responsrater 39% for HBV DNA < 300 kopier/ ml ved PCR, 79% for ALAT- normalisering, 26% for HBeAg- serokonvertering og 2% for HBsAg- serokonvertering (3% for HBsAg- tab).
For lamivudine (n = 355), cumulative response rates were 39% for HBV DNA < 300 copies/ ml by PCR, 79% for ALT normalisation, 26% for HBeAg seroconversion, and 2% for HBsAg seroconversion (3% for HBsAg loss).
Imens sås der ALAT- normalisering (≤ 1 gang ULN) hos 79% af de entecavir- behandlede og 68% af de lamivudin- behandlede patienter.
At end of dosing, among patients who continued treatment beyond 52 weeks (median of 96 weeks), 81% of 243 entecavir-treated and 39% of 164 lamivudine-treated patients had HBV DNA < 300 copies/ ml by PCR while ALT normalisation (≤ 1 times ULN) occurred in 79% of entecavir- treated and 68% of lamivudine-treated patients.
Behandling med entecavir i op til 96 uger (n = 325) gav kumulative responsrater på 94% for HBV DNA < 300 kopier/ ml ved PCR og 89% for ALAT- normalisering versus 77% for HBV DNA < 300 kopier/ ml ved PCR og 84% for ALAT- normalisering for lamivudin - behandlede patienter (n = 313).
HBeAg negative (study 027): treatment with entecavir up to 96 weeks (n = 325) resulted in cumulative response rates of 94% for HBV DNA < 300 copies/ ml by PCR and 89% for ALT normalisation versus 77% for HBV DNA < 300 copies/ ml by PCR and 84% for ALT normalisation for lamivudine-treated patients (n = 313).
For 26 entecavir- behandlede og 28 lamivudin- behandlede patienter som fortsatte behandling ud over de 52 uger (i gennemsnit 96 uger), havde 96% af de entecavir- behandlede og 64% af de lamivudin - behandlede patienter HBV DNA < 300 kopier/ ml ved PCR ved behandlingens afslutning.
For 26 entecavir-treated and 28 lamivudine-treated patients who continued treatment beyond 52 weeks (median 96 weeks), 96% of entecavir-treated and 64% of lamivudine-treated patients had HBV DNA < 300 copies/ ml by PCR at end of dosing.
Der sås ALAT- normalisering (≤ 1 gange ULN) hos 27% af de entecavir- behandlede og 21% af de lamivudin - behandlede patienter ved behandlingens afslutning.
ALT normalisation (≤ 1 times ULN) occurred in 27% of entecavir-treated and 21% of lamivudine-treated patients at end of dosing.
Responsen opretholdtes hos 75% (83/ 111) af entecavir- respondere vs 73% (68/ 93) af lamivudin- respondere i studie 022 og hos 46% (131/ 286) af entecavir- respondere vs 31% (79/ 253) af lamivudin- respondere i studie 027.
For patients who met protocol-defined response criteria, response was sustained throughout the 24-week post-treatment follow-up in 75% (83/ 111) of entecavir responders vs 73% (68/ 93) for lamivudine responders in study 022 and 46% (131/ 286) of entecavir responders vs 31% (79/ 253) for lamivudine responders in study 027.
Ved 48 ugers opfølgning efter behandling tabte et betragteligt antal HBeAg- negative patienter respons.
By 48 weeks of post-treatment follow-up, a substantial number of HBeAg negative patients lost response.
10 Lamivudin- refraktion:
Lamivudine-refractory:
HBeAg- positive (studie 026): behandling med entecavir i op til 96 uger (n = 141) gav kumulative responsrater på 30% for HBV DNA < 300 kopier/ ml ved PCR og 85% for ALAT- normalisering og 17% for HBeAg- serokonvertering.
HBeAg positive (study 026): treatment with entecavir for up to 96 weeks (n = 141) resulted in cumulative response rates of 30% for HBV DNA < 300 copies/ ml by PCR, 85% for ALT normalisation and 17% for HBeAg seroconversion.
For de 77 patienter, som fortsatte entecavirbehandling ud over de 52 uger (i gennemsnit 96 uger), havde 40% af patienterne HBV DNA < 300 kopier/ ml ved PCR, og 81% af patienterne havde ALAT - normalisering (≤ 1 gang ULN) ved behandlingens afslutning.
For the 77 patients who continued entecavir treatment beyond 52 weeks (median 96 weeks), 40% of patients had HBV DNA < 300 copies/ ml by PCR and 81% had ALT normalisation (≤ 1 times ULN) at end of dosing.
Alder/ køn:
Age/ gender:
Studie 038 inkluderede 67 HBeAg- positive patienter og 1 HBeAg- negativ patient med samtidig HIV- infektion.
Special populations HIV/ HBV co-infected patients receiving concomitant HAART: study 038 included 67 HBeAg positive and 1 HBeAg negative patients co-infected with HIV.
Patienterne havde stabil, kontrolleret HIV (HIV RNA < 400 kopier/ ml) med recidiv af HBV- viræmi i et lamivudin- indeholdende HAART- regime.
Patients had stable controlled HIV (HIV RNA < 400 copies/ ml) with recurrence of HBV viraemia on a lamivudine-containing HAART regimen.
HAART- regimet indeholdt ikke emtricitabin eller tenofovirdisoproxilfumerat.
HAART regimens did not include emtricitabine or tenofovir disoproxil fumarate.
De entecavir- behandlede patienter havde ved baseline tidligere været behandlet med lamivudin i gennemsnitligt 4, 8 år og havde et gennemsnitligt CD4- tal på 494 celler/ mm3 (kun 5 patienter havde CD4- tal < 200 celler/ mm3).
At baseline entecavir-treated patients had a median duration of prior lamivudine therapy of 4.8 years and median CD4 count of 494 cells/ mm3 (with only 5 subjects having CD4 count < 200 cells/ mm3).
Patienterne fortsatte deres lamivudin- regime og blev allokeret til tillæg af entecavir 1 mg, én gang daglig (n = 51) eller placebo (n = 17) i 24 uger efterfulgt af yderligere 24 uger, hvor alle fik entecavir.
Patients continued their lamivudine-regimen and were assigned to add either entecavir 1 mg once daily (n = 51) or placebo (n = 17) for 24 weeks followed by an additional 24 weeks where all received entecavir.
Ved 24 uger var fald i HBV viral load signifikant større med entecavir (- 3, 65 vs en stigning på 0, 11 log10 kopier/ ml).
At 24 weeks the reduction in HBV viral load was significantly greater with entecavir (-3.65 vs an increase of 0.11 log10 copies/ ml).
Der sås ALAT- normalisering hos 37% af patienterne med abnorm ALAT ved baseline, og ingen opnåede HBeAg- serokonvertering.
For patients originally assigned to entecavir treatment, the reduction in HBV DNA at 48 weeks was -4.20 log10 copies/ ml, ALT normalisation had occurred in 37% of patients with abnormal baseline ALT and none achieved HBeAg seroconversion.
Entecavir er ikke blevet evalueret hos HIV/ HBV- inficerede patienter, der ikke samtidig fik effektiv HIV- behandling.
10 HIV/ HBV co-infected patients not receiving concomitant HAART: entecavir has not been evaluated in HIV/ HBV co-infected patients not concurrently receiving effective HIV treatment.
Reduktioner i HIV- RNA er blevet rapporteret hos HIV/ HBV- inficerede patienter, der modtog entecavir- monoterapi uden HAART.
Reductions in HIV RNA have been reported in HIV/ HBV co-infected patients receiving entecavir monotherapy without HAART.
I nogle tilfælde er HIV- varianten M184V blevet observeret, som har implikation på valget af HAART- regimet, som patienten kan få i fremtiden.
In some cases, selection of HIV variant M184V has been observed, which has implications for the selection of HAART regimens that the patient may take in the future.
4. 4).
Therefore, entecavir should not be used in this setting due to the potential for development of HIV resistance (see section 4.4).
Et randomiseret, åbent studie (048), der sammenligner entecavir 1, 0 mg én gang daglig med adefovir 10 mg én gang daglig hos patienter med leverinkompensation, er igangværende.
Patients with decompensated liver disease: a randomised open-label study (048) comparing entecavir 1.0 mg once daily with adefovir 10 mg once daily in patients with hepatic decompensation is ongoing.
Patienter i kliniske forsøg, der initialt blev behandlet med entecavir 0, 5 mg (ikke tidligere behandlet med nukleosid) eller 1, 0 mg (lamivudin- refraktoriske), og hvor PCR HBV DNA er målt under behandling ved eller efter Uge 24, er monitorerede for resistens.
Clinical resistance: patients in clinical trials initially treated with entecavir 0.5 mg (nucleoside-naive) or 1.0 mg (lamivudine-refractory) and with an on-therapy PCR HBV DNA measurement at or after Week 24 were monitored for resistance.
Til og med Uge 240 blev der i forsøg med patienter, der ikke tidligere havde været behandlet med nukleosid, identificeret genotypeevidens for ETVr- substitutioner ved rtT184, rtS202 eller rtM250 hos 3 af patienterne, der blev behandlet med entecavir.
Through Week 240 in nucleoside-naive studies, genotypic evidence of ETVr substitutions at rtT184, rtS202, or rtM250 was identified in 3 patients treated with entecavir, 2 of whom experienced virologic breakthrough (see table).
Disse substitutioner sås kun ved tilstedeværelsen af LVDr- substitutioner (rtM204V og rtL180M).
These substitutions were observed only in the presence of LVDr substitutions (rtM204V and rtL180M).
11 Opståen af entecavir genotype- resistens til og med år 5 i forsøg med patienter, der ikke tidligere er behandlet med nukleosid
Emerging Genotypic Entecavir Resistance Through Year 5, Nucleoside-Naive Studies a
År 3a
Year 3
Patienter behandlet og monitoreret for b resistens Patienter i specifikt år med:
Patients treated and monitored for b resistance Patients in specific year with:
- opståen af c genotype- ETVr
c - emerging genotypic ETVr
- genotype- ETVrc med virologisk gennembrud Kumulativ sandsynlighed for:
c - genotypic ETVr with virologic d breakthrough Cumulative probability of:
- opståen af genotype- ETVr
- emerging genotypic ETVr
- genotype- ETVrc med virologisk gennembrud a
c - genotypic ETVr with virologic d breakthrough a
Resultater afspejler brug af 1- mg dosis af entecavir hos 147 ud af 149 patienter i år 3 og hos alle patienter i År 4 og 5 og i kombinationsbehandling med entecavir- lamivudin (efterfulgt af længerevarende entecavirbehandling) i gennemsnitlig 20 uger hos 130 ud af 149 patienter i År 3 og i 1 uge for 1 ud af 121 patienter i År 4 i et rollover- forsøg. b Inkluderer patienter med mindst én HBV DNA- måling under behandling ved PCR ved eller efter uge 24 til og med uge 58 (År 1), efter uge 58 til og med uge 102 (År 2) eller efter uge 102 til og med uge 156 (År 3), efter uge 156 til og med uge 204 (År 4) eller efter uge 204 til og med uge 252 (År 5). c Patienterne skal også have LVDr- substitutioner. d ≥ 1 log10 stigning over nadir i HBV DNA ved PCR, bekræftet ved på hinanden følgende målinger eller ved afslutningen af tidsvinduet.
Results reflect use of a 1-mg dose of entecavir for 147 of 149 patients in Year 3 and all patients in Years 4 and 5 and of combination entecavir-lamivudine therapy (followed by long-term entecavir therapy) for a median of 20 weeks for 130 of 149 patients in Year 3 and for 1 week for 1 of 121 patients in Year 4 in a rollover study. b Includes patients with at least one on-therapy HBV DNA measurement by PCR at or after week 24 through week 58 (Year 1), after week 58 through week 102 (Year 2), after week 102 through week 156 (Year 3), after week 156 through week 204 (Year 4), or after week 204 through week 252 (Year 5). c Patients also have LVDr substitutions. d ≥ 1 log10 increase above nadir in HBV DNA by PCR, confirmed with successive measurements or at the end of the windowed time point.
Dette indikerer at tidligere lamivudinbehandling kan selektere disse resistenssubstitutioner, og at de kan eksistere i mindre grad inden entecavirbehandling.
ETVr substitutions (in addition to LVDr substitutions rtM204V/ I ± rtL180M) were observed at baseline in isolates from 10/ 187 (5%) lamivudine-refractory patients treated with entecavir and monitored for resistance, indicating that prior lamivudine treatment can select these resistance substitutions and that they can exist at a low frequency before entecavir treatment.
Til og med Uge 240 oplevede 3 ud af de 10 patienter virologisk gennembrud (≥ 1 log10 stigning over nadir).
Through Week 240, 3 of the 10 patients experienced virologic breakthrough (≥ 1 log10 increase above nadir).
Opståen af entecavirresistens i lamivudinrefraktoriske studier til og med Uge 240 opsummeres i tabellen.
Emerging entecavir resistance in lamivudine-refractory studies through Week 240 is summarized in the table.
12 Opståen af entecavir genotype- resistens til og med År 5, lamivudin- refraktoriske forsøg
11 Genotypic Entecavir Resistance Through Year 5, Lamivudine-Refractory Studies
Patienter behandlet og monitoreret b for resistens Patienter i specifikt år med:
Patients treated and monitored for b resistance Patients in specific year with:
- Opståen af genotype- ETVr
- emerging genotypic ETVr
2e
e
14e
e 14
13e
e 13
9e
e 9
1e
e 1
1, 1% e
e
10, 7% e
e 10.7%
27% e
e 27%
41, 3% e
e 41.3%
43, 6% e
e
Resultater afspejler kombinationsbehandling med entecavir- lamivudin i gennemsnit i 13 uger (efterfulgt af længerevarende behandling med entecavir) hos 48 ud af 80 patienter i År 3, i gennemsnit 38 uger for 10 ud af 52 patienter i År 4 og i 16 uger for 1 ud af 33 patienter i År 5 i et rollover- forsøg. b Inkluderer patienter med mindst én HBV DNA- måling under behandling ved PCR ved eller efter uge 24 til og med Uge 58 (År 1), efter uge 58 til og med uge 102 (År 2) eller efter uge 102 til og med uge 156 (År 3), efter uge 156 til og med uge 204 (År 4) eller efter uge 204 til og med uge 252 (År 5). c Patienterne skal også have LVDr- substitutioner. d ≥ 1 log10 stigning over nadir i HBV DNA ved PCR, bekræftet ved på hinanden følgende målinger eller ved afslutningen af tidsvinduet. e ETVr der forekommer i et givent år, virologisk gennembrud i det specificerede år.
Results reflect use of combination entecavir-lamivudine therapy (followed by long-term entecavir therapy) for a median of 13 weeks for 48 of 80 patients in Year 3, a median of 38 weeks for 10 of 52 patients in Year 4, and for 16 weeks for 1 of 33 patients in Year 5 in a rollover study. b Includes patients with at least one on-therapy HBV DNA measurement by PCR at or after week 24 through week 58 (Year 1), after week 58 through week 102 (Year 2), after week 102 through week 156 (Year 3), after week 156 through week 204 (Year 4), or after week 204 through week 252 (Year 5). c Patients also have LVDr substitutions. d ≥ 1 log10 increase above nadir in HBV DNA by PCR, confirmed with successive measurements or at the end of the windowed time point. e ETVr occurring in any year; virologic breakthrough in specified year.
Blandt lamivudin- refraktoriske patienter med baseline HBV DNA < 107 log10 kopier/ ml opnåede 64% (9/ 14) HBV DNA < 300 kopier/ ml i Uge 48.
Among lamivudine-refractory patients with baseline HBV DNA < 107 log10 copies/ ml, 64% (9/ 14) achieved HBV DNA < 300 copies/ ml at Week 48.
Disse 14 patienter havde en lavere forekomst af genotype entecavir- resistens (kumulativ sandsynlighed på 18, 8% i 5 års opfølgningsperiode) end den samlede forsøgspopulation (se tabel).
These 14 patients had a lower rate of genotypic entecavir resistance (cumulative probability 18.8% through 5 years of follow-up) than the overall study population (see table).
Ligeledes havde lamivudin- refraktoriske patienter, som opnåede HBV DNA < 104 log10 kopier/ ml ved PCR i Uge 24, en lavere forekomst af resistens end de patienter, der ikke opnåede denne HBV DNA (kumulativ sandsynlighed over 5 år på henholdsvis 17, 6% [n=50] versus 60, 5% [n=135]).
Also, lamivudine-refractory patients who achieved HBV DNA < 104 log10 copies/ ml by PCR at Week 24 had a lower rate of resistance than those who did not (5-year cumulative probability 17.6% [n=50] versus 60.5% [n=135], respectively).
Entecavir absorberes hurtigt, og maksimal plasmakoncentration nås efter 0, 5 - 1, 5 time.
Absorption: entecavir is rapidly absorbed with peak plasma concentrations occurring between 0.5-1.5 hours.
Der er en dosisproportional stigning i Cmax og AUC- værdier efter gentagne doser på 0, 1 - 1 mg.
There is a dose- proportionate increase in Cmax and AUC values following multiple doses ranging from 0.1-1 mg.
Steady- state opnås 6 - 10 dage efter én gang daglig dosering med ≈ 2 gange akkumulering.
Steady-state is achieved between 6-10 days after once daily dosing with ≈ 2 times accumulation.
Cmax og Cmin ved steady- state er henholdsvis 4, 2 og 0, 3 ng/ ml for en dosis på 0, 5 mg, og henholdsvis 8, 2 og 0, 5 ng/ ml for 1 mg.
Cmax and Cmin at steady-state are 4.2 and 0.3 ng/ ml, respectively, for a dose of 0.5 mg, and 8.2 and 0.5 ng/ ml, respectively, for 1 mg.
Administration af 0, 5 mg entecavir med et fedtrigt standardmåltid (945 kcal, 54, 6 g fedt) eller et let måltid (379 kcal, 8, 2 g fedt) forårsagede en minimal forsinkelse i absorption (1 - 1, 5 time fed vs.
Administration of 0.5 mg entecavir with a standard high-fat meal (945 kcal, 54.6 g fat) or a light meal (379 kcal, 8.2 g fat) resulted in a minimal delay in absorption (1-1.5 hour fed vs.
0, 75 time fastende), et fald i Cmax på 44 - 46% samt et fald i AUC på 18 - 20%.
0.75 hour fasted), a decrease in Cmax of 44-46%, and a decrease in AUC of 18-20%.
4. 2).
The lower Cmax and AUC when taken with food is not considered to be of clinical relevance in nucleoside-naive patients but could affect efficacy in lamivudine-refractory patients (see section 4.2).
Det estimerede fordelingsvolumen for entecavir er større end kroppens totale vandindhold.
Distribution: the estimated volume of distribution for entecavir is in excess of total body water.
Entecavir er ikke et substrat af og virker ikke inducerende eller hæmmende på CYP450 - enzymsystemet.
Metabolism: entecavir is not a substrate, inhibitor or inducer of the CYP450 enzyme system.