natgillin/translations-raw huggingface dataset:
Ved uge 24 var den tidsvægtede gennemsnitsændring fra baseline i log10 plasmakoncentrationer af HIV- 1- RNA niveauer (DAVG24) - 0, 03 log10 kopier/ ml og - 0, 61 log10 kopier/ ml for placebogruppen og tenofovirdisoproxil 245 mg (som fumarat) gruppen (p < 0, 0001).
At week 24 the time-weighted average change from baseline in log10 plasma HIV-1 RNA levels (DAVG24) was -0.03 log10 copies/ ml and -0.61 log10 copies/ ml for the placebo and tenofovir disoproxil 245 mg (as fumarate) recipients (p < 0.0001).
En statistisk signifikant forskel til gunst for tenofovirdisoproxil 245 mg (som fumarat) sås i den tidsvægtede gennemsnitsændring fra baseline efter 24 uger (DAVG24) for CD4- celletallet (+13 celler/ mm3 for tenofovirdisoproxil 245 mg (som fumarat) versus - 11 celler/ mm3 for placebo, p- værdi = 0, 0008).
A statistically significant difference in favour of tenofovir disoproxil 245 mg (as fumarate) was seen in the time-weighted average change from baseline at week 24 (DAVG24) for CD4 count (+13 cells/ mm3 for tenofovir disoproxil 245 mg (as fumarate) versus -11 cells/ mm3 for placebo, p-value = 0.0008).
41% og 18%).
The antiviral response to tenofovir disoproxil fumarate was durable through 48 weeks (DAVG48 was -0.57 log10 copies/ ml, proportion of patients with HIV-1 RNA below 400 or 50 copies/ ml was 41% and 18% respectively).
Otte patienter (2%) behandlet med tenofovirdisoproxil 245 mg (som fumarat) udviklede K65R mutationen inden for de første 48 uger.
Eight (2%) tenofovir disoproxil 245 mg (as fumarate) treated patients developed the K65R mutation within the first 48 weeks.
Den 144- ugers, dobbeltblinde, aktivt kontrollerede fase af undersøgelse GS- 99- 903 vurderede effekten og sikkerheden af tenofovirdisoproxil 245 mg (som fumarat) versus stavudin ved anvendelse i kombination med lamivudin og efavirenz hos behandlingsnaive HIV- 1- inficerede patienter.
The 144-week, double-blind, active controlled phase of study GS-99-903 evaluated the efficacy and safety of tenofovir disoproxil 245 mg (as fumarate) versus stavudine when used in combination with lamivudine and efavirenz in HIV-1 infected patients naïve to antiretroviral therapy.
Det gennemsnitlige CD4- celletal ved baseline var 279 celler/ mm3, den gennemsnitlige plasmakoncentration af HIV- 1- RNA ved baseline var 4, 91 log10 kopier/ ml, 19% af patienterne havde symptomatisk HIV- 1- infektion og 18% havde AIDS.
The mean baseline CD4 cell count was 279 cells/ mm3, the mean baseline plasma HIV-1 RNA was 4.91 log10 copies/ ml, 19% of patients had symptomatic HIV-1 infection and 18% had AIDS.
Patienter blev stratificeret efter HIV- 1- RNA og CD4- tal ved baseline.
Patients were stratified by baseline HIV-1 RNA and CD4 count.
43% af patienterne havde en virusmængde ved baseline på > 100. 000 kopier/ ml og 39% havde CD4- celletal på < 200 celler/ ml.
Forty-three percent of patients had baseline viral loads > 100,000 copies/ ml and 39% had CD4 cell counts < 200 cells/ ml.
I uge 144 var procentdelen af patienter med HIV- 1- RNA under 400 kopier/ ml og 50 kopier/ ml hhv.
By intent to treat analysis (Missing data and switch in antiretroviral therapy (ART) considered as failure), the proportion of patients with HIV-1 RNA below 400 copies/ ml and 50 copies/ ml at 48 weeks of treatment was 80% and 76% respectively in the tenofovir disoproxil 245 mg (as fumarate) arm, compared to 84% and 80% in the stavudine arm.
71% og 68% i tenofovirdisoproxil 245 mg (som fumarat) - armen sammenlignet med 64% og 63% i stavudinarmen.
At 144 weeks, the proportion of patients with HIV-1 RNA below 400 copies/ ml and 50 copies/ ml was 71% and 68% respectively in the tenofovir disoproxil 245 mg (as fumarate) arm, compared to 64% and 63% in the stavudine arm.
Den gennemsnitlige ændring fra baseline for HIV- 1- RNA og CD4- tal i uge 48 af behandlingen var næsten ens i begge behandlingsgrupper (- 3, 09 og - 3, 09 log10 kopier/ ml; +169 og 167 celler/ mm3 i hhv. tenofovirdisoproxil 245 mg (som fumarat) og stavudin gruppen).
The average change from baseline for HIV-1 RNA and CD4 count at 48 weeks of treatment was similar in both treatment groups (-3.09 and -3.09 log10 copies/ ml; +169 and 167 cells/ mm3 in the tenofovir disoproxil 245 mg (as fumarate) and stavudine groups, respectively).
I uge 144 af behandlingen forblev den gennemsnitlige ændring fra baseline næsten ens i begge behandlingsgrupper (- 3, 07 og - 3, 03 log10 kopier/ ml; +263 og +283 celler/ mm3 i hhv. tenofovirdisoproxil 245 mg (som fumarat) - gruppen og stavudingruppen).
At 144 weeks of treatment, the average change from baseline remained similar in both treatment groups (-3.07 and -3.03 log10 copies/ ml; +263 and +283 cells/ mm3 in the tenofovir disoproxil 245 mg (as fumarate) and stavudine groups, respectively).
En konsistent respons på behandling med tenofovirdisoproxil 245 mg (som fumarat) sås uden hensyn til HIV- 1- RNA og CD4- tal ved baseline.
A consistent response to treatment with tenofovir disoproxil 245 mg (as fumarate) was seen regardless of baseline HIV-1 RNA and CD4 count.
K65R- mutationen sås hos en lidt højere procentdel af patienter i tenofovirdisoproxilfumarat gruppen end den aktive kontrolgruppe (2, 7% versus 0, 7%).
13 The K65R mutation occurred in a slightly higher percentage of patients in the tenofovir disoproxil fumarate group than the active control group (2.7% versus 0.7%).
Efavirenz - eller lamivudin- resistens opstod enten forud for eller samtidig med udviklingen af K65R i alle tilfælde.
Efavirenz or lamivudine resistance either preceded or was coincident with the development of K65R in all cases.
Otte patienter i tenofovirdisoproxil 245 mg (som fumarat) - armen havde HIV med K65R- mutation, 7 af disse opstod i løbet af de første 48 uger af behandlingen og den sidste i uge 96.
Eight patients had HIV that expressed K65R in the tenofovir disoproxil 245 mg (as fumarate) arm, 7 of these occurred during the first 48 weeks of treatment and the last one at week 96.
Fra både genotype - og fænotypeanalyser har der ikke været nogle tegn på andre veje for resistens over for tenofovir.
From both the genotypic and phenotypic analyses there was no evidence for other pathways of resistance to tenofovir.
Data vedrørende HBV:
Data pertaining to HBV:
HBV- antiviral aktivitet in vitro:
HBV antiviral activity in vitro:
Tenofovirs antivirale aktivitet in vitro over for HBV blev vurderet i cellelinjen HepG2 2. 2. 15.
The in vitro antiviral activity of tenofovir against HBV was assessed in the HepG2 2.2.15 cell line.
EC50- værdierne for tenofovir var inden for intervallet 0, 14 til 1, 5 µmol/ l med CC50- værdier (50% cytotoksisk koncentration) > 100 µmol/ l.
The EC50 values for tenofovir were in the range of 0.14 to 1.5 µmol/ l, with CC50 (50% cytotoxicity concentration) values > 100 µmol/ l.
Der er ikke blevet identificeret nogle HBV- mutationer i forbindelse med tenofovirdisoproxilfumarat- resistens (se Kliniske resultater).
No HBV mutations associated with tenofovir disoproxil fumarate resistance have been identified (see Clinical results).
I cellebaserede assays med HBV- stammer med rtV173L -, rtL180M - og rtM204I/ V- mutationer i forbindelse med lamivudin - og telbivudin- resistens påvistes en følsomhed over for tenofovir fra 0, 7 til 3, 4 gange den for vildtypevirus.
In cell based assays, HBV strains expressing the rtV173L, rtL180M, and rtM204I/ V mutations associated with resistance to lamivudine and telbivudine showed a susceptibility to tenofovir ranging from 0.7- to 3.4-fold that of wild-type virus.
HBV- stammer med rtL180M -, rtT184G -, rtS202G/ I -, rtM204V - og rtM250V - mutationer i forbindelse med entecavir- resistens udviste en følsomhed over for tenofovir fra 0, 6 til 6, 9 gange den for vildtypevirus.
HBV strains expressing the rtL180M, rtT184G, rtS202G/ I, rtM204V and rtM250V mutations associated with resistance to entecavir showed a susceptibility to tenofovir ranging from 0.6- to 6.9-fold that of wild- type virus.
HBV- stammer med rtA181V - og rtN236T- mutationer i forbindelse med adefovir- resistens udviste en følsomhed over for tenofovir fra 2, 9 til 10 gange den for vildtypevirus.
HBV strains expressing the adefovir-associated resistance mutations rtA181V and rtN236T showed a susceptibility to tenofovir ranging from 2.9- to 10-fold that of wild-type virus.
Virus, som indeholdt rtA181T- mutatationen, forblev følsomme over for tenofovir med EC50- værdier på 1, 5 gange den for vildtypevirus.
Viruses containing the rtA181T mutation remained susceptible to tenofovir with EC50 values 1.5-fold that of wild-type virus.
Påvisningen af tenofovirdisoproxilfumarats gavnlige effekt er baseret på histologisk, virologisk, biokemisk og serologisk respons hovedsageligt hos behandlingsnaive voksne med HBeAg- positiv og HBeAg- negativ kronisk hepatitis B med kompenseret leversygdom.
The demonstration of benefit of tenofovir disoproxil fumarate is based on histological, virological, biochemical and serological responses mainly in treatment-naïve adults with HBeAg positive and HBeAg negative chronic hepatitis B with compensated liver disease.
Erfaring hos patienter med kompenseret leversygdom:
Experience in patients with compensated liver disease:
Resultater gennem 48 uger fra to randomiserede, dobbeltblinde fase 3- undersøgelser, som sammenlignede tenofovirdisoproxilfumarat med adefovirdipivoxil hos patienter med kompenseret leversygdom, vises i tabel 2 nedenfor.
Results through 48 weeks from two randomised, phase 3 double-blind studies comparing tenofovir disoproxil fumarate to adefovir dipivoxil in patients with compensated liver disease are presented in Table 2 below.
Undersøgelse GS- US- 174- 0103 blev udført med 266 (randomiserede og behandlede) HBeAg- positive patienter, mens undersøgelse GS- US- 174- 0102 blev udført med 375 (randomiserede og behandlede) patienter, som var HBeAg- negative og HBeAb- positive.
Study GS-US-174-0103 was conducted in 266 (randomised and treated) HBeAg positive patients while study GS-US-174-0102 was conducted in 375 (randomised and treated) patients negative for HBeAg and positive for HBeAb.
I begge disse undersøgelser var tenofovirdisoproxilfumarat signifikant bedre end adefovirdipivoxil med hensyn til det primære virkningsendepunkt, som var komplet respons (defineret som HBV- DNA- niveauer < 400 kopier/ ml og en forbedring af Knodell' s nekroinflammatoriske score på mindst 2 points uden forværring af Knodell' s fibrosescore).
In both of these studies tenofovir disoproxil fumarate was significantly superior to adefovir dipivoxil for the primary efficacy endpoint of complete response (defined as HBV DNA levels < 400 copies/ ml and Knodell necroinflammatory score improvement of at least 2 points without worsening in Knodell fibrosis).
Begge behandlinger
Treatment with tenofovir disoproxil 245 mg (as fumarate) was also associated with significantly greater proportions of patients with HBV DNA < 400 copies/ ml, when compared to adefovir dipivoxil 10 mg treatment.
14 producerede lignende resultater med hensyn til histologisk respons (defineret som en forbedring af Knodell' s nekroinflammatoriske score på mindst 2 points uden forværring af Knodell' s fibrosescore) ved uge 48 (se tabel 2 nedenfor).
Both treatments produced similar results with regard to histological response (defined as Knodell necroinflammatory score improvement of at least 2 points without worsening in Knodell fibrosis) at week 48 (see Table 2 below).
In undersøgelse GS- US- 174- 0103 var der en signifikant større andel af patienterne i tenofovirdisoproxilfumarat- gruppen, der havde normaliseret ALAT og opnået fald i HBsAg ved uge 48 end i adefovirdipivoxil- gruppen (se tabel 2 nedenfor).
In study GS-US-174-0103 a significantly greater proportion of patients in the tenofovir disoproxil fumarate group than in the adefovir dipivoxil group had normalised ALT and achieved HBsAg loss at week 48 (see Table 2 below).
Tabel 2:
14 Table 2:
Virkningsparametre i kompenserede HBeAg- positive og HBeAg- negative patienter ved uge 48
Efficacy parameters in compensated HBeAg positive and HBeAg negative patients at week 48
Undersøgelse 174- 0102 (HBeAg- negative)
Study 174-0102 (HBeAg negative)
Undersøgelse 174- 0103 (HBeAg- positive)
Study 174-0103 (HBeAg positive)
Tenofovirdisoproxil Adefovirdipivoxil 245 mg (som 10 mg fumarat) n = 125 n = 250
10
Tenofovirdisoproxil Adefovirdipivoxil 245 mg (som 10 mg fumarat) n = 90 n = 176
10
Komplet respons (%) a Histologi
Complete response (%)a Histology
71 * 49
49 67*
67 * 12
12
Histologisk respons (%) b
Histological response (%)b
72 69
72
74 68
68
Median HBV DNA - reduktion fra baselinec (log10 kopier/ ml) HBV- DNA (%)
Median HBV DNA reduction from baselinec (log10 copies/ ml) HBV DNA (%)
- 4, 7 * - 4, 0
-4.7*
- 6, 4 * - 3, 7
-4.0 -6.4*
< 400 kopier/ ml (< 69 IU/ ml) ALAT (%)
< 400 copies/ ml (< 69 IU/ ml) ALT (%)
93 * 63
63 76*
76 * 13
13
Normaliseret ALATd Serologi (%)
Normalised ALTd Serology (%)
76 77
76
68 * 54
54
Fald i HBeAg/ sero - konversion
HBeAg loss/ seroconversion
22/ 21 18/ 18
18/ 18
Fald i HBsAg/ sero - konversion
HBsAg loss/ seroconversion
0/ 0 0/ 0
0/ 0 0/ 0
3 * / 1 0/ 0
0/ 0
* p- værdi versus adefovirdipivoxil < 0, 05, aKomplet respons defineret som HBV- DNA- niveauer < 400 kopier/ ml og en forbedring af Knodell' s nekroinflammatoriske score på mindst 2 points uden forværring af Knodell' s fibrosescore, b Forbedring af Knodell' s nekroinflammatoriske score på mindst 2 points uden forværring af Knodell' s fibrosescore, c Median ændring fra baseline HBV DNA reflekterer blot forskellen mellem baseline HBV DNA og analysens detektionsgrænse (Limit of detection - LOD), d Populationen, som blev brugt til analyse af ALAT- normalisering, inkluderede kun patienter med ALAT over ULN ved baseline.
* p-value versus adefovir dipivoxil < 0.05, a Complete response defined as HBV DNA levels < 400 copies/ ml and Knodell necroinflammatory score improvement of at least 2 points without worsening in Knodell fibrosis, b Knodell necroinflammatory score improvement of at least 2 points without worsening in Knodell fibrosis, c Median change from baseline HBV DNA merely reflects the difference between baseline HBV DNA and the limit of detection (LOD) of the assay, d The population used for analysis of ALT normalisation included only patients with ALT above ULN at baseline.
Tenofovirdisoproxilfumarat var forbundet med signifikant større andele af patienter med HBV- DNA, som ikke kunne måles (< 169 kopier/ ml [< 29 IU/ ml]; kvantificeringsgrænsen for Roche Cobas Taqman HBV- assayet), sammenlignet med adefovirdipivoxil (undersøgelse GS- US- 174- 0102; 91%, 56% henholdsvis undersøgelse GS- US- 174- 0103; 69%, 9%).
Tenofovir disoproxil fumarate was associated with significantly greater proportions of patients with undetectable HBV DNA (< 169 copies/ ml [< 29 IU/ ml]; the limit of quantification of the Roche Cobas Taqman HBV assay), when compared to adefovir dipivoxil (study GS-US-174-0102; 91%, 56% and study GS-US-174-0103; 69%, 9%), respectively.
Behandlingsresponsen med tenofovirdisoproxilfumarat var sammenlignelig hos de nukleosid- behandlede (n = 51) og nukleosid- naive (n = 375) patienter samt hos patienter med normal
Response to treatment with tenofovir disoproxil fumarate was comparable in nucleoside-experienced (n = 51) and nucleoside-naïve (n = 375) patients and in patients with normal ALT (n = 21) and abnormal ALT (n = 405) at baseline when studies GS-US-174-0102 and GS-US-174-0103 were combined.
Der var 49 ud af de 51 nukleosid- behandlede patienter, der tidligere var blevet behandlet med lamivudin.
Forty-nine of the 51 nucleoside-experienced patients were previously treated with lamivudine.
Der var 73% af de nukleosid- behandlede og 69% af de nukleosid- naive patienter, der opnåede fuldkommen respons på behandlingen; 90% af de nukleosid- naive og 88% af de nukleosid- behandlede patienter opnåede HBV- DNA– suppresion < 400 kopier/ ml.
Seventy-three percent of nucleoside-experienced and 69% of nucleoside-naïve patients achieved complete response to treatment; 90% of nucleoside-naïve and 88% of nucleoside-experienced patients achieved HBV DNA suppression < 400 copies/ ml.
Alle patienter med normal ALAT ved baseline og 88% af patienterne med unormal ALAT ved baseline opnåede HBV- DNA- suppresion < 400 kopier/ ml.
All patients with normal ALT at baseline and 88% of patients with abnormal ALT at baseline achieved HBV DNA suppression < 400 copies/ ml.
I en randomiseret 48- ugers dobbeltblind, kontrolleret undersøgelse af tenofovirdisoproxil 245 mg (som fumarat) hos patienter med samtidig infektion med HIV- 1 og kronisk hepatitis B, der tidligere blev behandlet med lamivudin (undersøgelse ACTG 5127), var de gennemsnitlige serum- HBV- DNA- niveauer ved baseline på 9, 45 log10 kopier/ ml (n = 27) hos de patienter, der var randomiseret til tenofovir- armen.
In a randomised, 48-week double-blind, controlled study of tenofovir disoproxil 245 mg (as fumarate) in patients co-infected with HIV-1 and chronic hepatitis B with prior lamivudine experience (study ACTG 5127), the mean serum HBV DNA levels at baseline in patients randomised to the tenofovir
Behandling med tenofovirdisoproxil 245 mg (som fumarat) var forbundet med en gennemsnitlig ændring i serum- HBV- DNA fra baseline på - 5, 74 log10 kopier/ ml (n = 18) hos de patienter, hvor der fandtes 48- ugers data.
Treatment with tenofovir disoproxil 245 mg (as fumarate) was associated with a mean change in serum HBV DNA from baseline, in the patients for whom there was 48-week data, of -5.74 log10 copies/ ml (n = 18).
Ydermere havde 61% af patienterne normale ALAT- værdier ved uge 48.
In addition, 61% of patients had normal ALT at week 48.
Erfaring hos patienter med vedvarende viral replikation:
Experience in patients with persistent viral replication:
Virkningen og sikkerheden af tenofovirdisoproxil 245 mg (som fumarat) eller tenofovirdisoproxil 245 mg (som fumarat) sammen med 200 mg emtricitabin er ved at blive evalueret i en randomiseret dobbelt- blind undersøgelse (undersøgelse GS- US- 174- 0106) med HBeAg- positive og HBeAg- negative patienter, som havde vedvarende viræmi (HBV- DNA ≥ 1. 000 kopier/ ml), mens de fik adefovirdipivoxil 10 mg i mere end 24 uger.
The efficacy and safety of tenofovir disoproxil 245 mg (as fumarate) or tenofovir disoproxil 245 mg (as fumarate) plus 200 mg emtricitabine is being evaluated in a randomised, double-blind study (study GS-US-174-0106), in HBeAg positive and HBeAg negative patients who had persistent viraemia (HBV DNA ≥ 1,000 copies/ ml) while receiving adefovir dipivoxil 10 mg for more than 24 weeks.
Ved uge 24 var det overordnede resultat af en tenofovir- holdig behandling, at 77% (46/ 60) af patienterne havde HBV- DNA < 400 kopier/ ml (< 69 IU/ ml), og 62% (37/ 60) af patienterne havde HBV- DNA under detektionsgrænsen (< 169 kopier/ ml [< 29 IU/ ml]; kvantificeringsgrænsen med Roche Cobas TaqMan HBV- assayet).
Overall at week 24, treatment with a tenofovir-containing regimen resulted in 77% (46/ 60) of patients with HBV DNA < 400 copies/ ml (< 69 IU/ ml) and 62% (37/ 60) of patients with undetectable HBV DNA (below 169 copies/ ml [< 29 IU/ ml]; the limit of quantification of the Roche Cobas TaqMan HBV assay).
Ydermere var den procentvise andel af patienter med normal ALAT 68% (42/ 62) ved uge 24.
In addition, at week 24, the percentage of patients who had normal ALT was 68% (42/ 62).
Der var 426 HBeAg- negative (GS- US- 174- 0102, n = 250) og HBeAg- positive (GS- US- 174- 0103, n = 176) patienter, der blev undersøgt for genotype- ændringer i HBV- polymerase.
Four hundred and twenty-six HBeAg negative (GS-US-174-0102, n = 250) and HBeAg positive (GS-US-174-0103, n = 176) patients were evaluated for genotypic changes in HBV polymerase.
Genotype- undersøgelser blev udført hos alle patienter med HBV- DNA > 400 kopier/ ml ved uge 48.
Genotypic evaluations were performed on all patients with HBV DNA > 400 copies/ ml at week 48.
Der blev ikke identificeret nogen mutationer med forbindelse til tenofovirdisoproxilfumarat- resistens.
No mutations associated with tenofovir disoproxil fumarate resistance have been identified.
Tenofovirdisoproxilfumarat er et vandopløseligt ester- prodrug, som in vivo hurtigt omdannes til tenofovir og formaldehyd.
Tenofovir disoproxil fumarate is a water soluble ester prodrug which is rapidly converted in vivo to tenofovir and formaldehyde.
Absorption Efter oral indgivelse af tenofovirdisoproxilfumarat til HIV- inficerede patienter absorberes tenofovirdisoproxilfumarat hurtigt og omdannes til tenofovir.
Absorption Following oral administration of tenofovir disoproxil fumarate to HIV infected patients, tenofovir disoproxil fumarate is rapidly absorbed and converted to tenofovir.
326 (36, 6%) ng/ ml, 3. 324 (41, 2%) ng· t/ ml og 64, 4 (39, 4%) ng/ ml.
Administration of multiple doses of tenofovir disoproxil fumarate with a meal to HIV infected patients resulted in mean (%CV) tenofovir Cmax, AUC0-∞, and Cmin values of 326 (36.6%) ng/ ml, 3,324 (41.2%) ng·h/ ml and 64.4 (39.4%) ng/ ml, respectively.
Den orale biotilgængelighed af tenofovir fra tenofovirdisoproxilfumarat var ca.
Maximum tenofovir concentrations are observed in serum within one hour of dosing in the fasted state and within two hours when taken with food.
25% hos fastende patienter.
The oral bioavailability of tenofovir from tenofovir disoproxil fumarate in fasted patients was approximately 25%.
14%.
Administration of tenofovir disoproxil fumarate with a high fat meal enhanced the oral bioavailability, with an increase in tenofovir AUC by approximately 40% and Cmax by approximately 14%.
Efter den første dosis tenofovirdisoproxilfumarat varierede medianværdien Cmax i serum fra 213 til 375 ng/ ml hos patienter, der havde indtaget et måltid.
Following the first dose of tenofovir disoproxil fumarate in fed patients, the median Cmax in serum ranged from 213 to 375 ng/ ml.
800 ml/ kg.
Distribution Following intravenous administration the steady-state volume of distribution of tenofovir was estimated to be approximately 800 ml/ kg.
Efter oral indgivelse af tenofovirdisoproxilfumarat fordeles tenofovir til de fleste væv, hvor de højeste koncentrationer forekommer i nyrer, lever og tarmindhold (prækliniske undersøgelser).
After oral administration of tenofovir disoproxil fumarate, tenofovir is distributed to most tissues with the highest concentrations occurring in the kidney, liver and the intestinal contents (preclinical studies).
In vitro- proteinbinding af tenofovir til plasma - eller serumprotein var under henholdsvis 0, 7 og 7, 2% gennem tenofovirs koncentrationsområde 0, 01 til 25 µg/ ml.
In vitro protein binding of tenofovir to plasma or serum protein was less than 0.7 and 7.2%, respectively, over the tenofovir concentration range 0.01 to 25 µg/ ml.
Biotransformation In vitro- undersøgelser har afgjort, at hverken tenofovirdisoproxilfumarat eller tenofovir er substrater for CYP450- enzymerne.
Biotransformation In vitro studies have determined that neither tenofovir disoproxil fumarate nor tenofovir are substrates for the CYP450 enzymes.
300 gange) end dem, der sås in vivo, hæmmede tenofovir ikke in vitro- lægemiddelmetabolisering medieret af en hvilken som helst af de vigtige, humane CYP450- isoformer, der er involveret i lægemiddelbiotransformation (CYP3A4, CYP2D6, CYP2C9, CYP2E1 eller CYP1A1/ 2).
Tenofovir disoproxil fumarate at a concentration of 100 µmol/ l had no
Tenofovirdisoproxilfumarat i en koncentration på 100 µmol/ l havde ingen effekt på nogen af CYP450 - isoformerne undtagen CYP1A1/ 2, hvor der sås en lille (6%), men statistisk signifikant reduktion i metaboliseringen af CYP1A1/ 2- substrat.
16 effect on any of the CYP450 isoforms, except CYP1A1/ 2, where a small (6%) but statistically significant reduction in metabolism of CYP1A1/ 2 substrate was observed.
70- 80% af dosen udskilles uomdannet i urinen efter intravenøs indgivelse.
Elimination Tenofovir is primarily excreted by the kidney by both filtration and an active tubular transport system with approximately 70-80% of the dose excreted unchanged in urine following intravenous administration.
300 ml/ min).
Total clearance has been estimated to be approximately 230 ml/ h/ kg (approximately 300 ml/ min).