natgillin/translations-raw huggingface dataset:
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.
144 tednov trajajoča, dvojno slepa, aktivno kontrolirana faza študije GS- 99- 903 je ocenjevala učinkovitost in varnost 245 mg tenofovirdizoproksila (v obliki fumarata) napram stavudinu pri uporabi v kombinaciji z lamivudinom in efavirenzom pri bolnikih okuženih s HIV- 1, še nezdravljenih s protiretrovirusnimi zdravili.
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.
Ob začetku študije je bilo srednje število CD4 celic 279 celic/ mm3, srednja plazemska koncentracija HIV- 1 RNA 4, 91 log10 kopij/ ml; 19% bolnikov je imelo simptome okužbe s HIV- 1 in 18% je imelo AIDS.
Patients were stratified by baseline HIV-1 RNA and CD4 count.
Bolniki so bili razvrščeni glede na začetno vrednost HIV- 1 RNA in števila CD4 celic.
Forty-three percent of patients had baseline viral loads > 100,000 copies/ ml and 39% had CD4 cell counts < 200 cells/ ml.
43% bolnikov je imelo začetno vrednost virusne obremenitve > 100. 000 kopij/ ml in 39% je imelo število CD4 celic < 200 celic/ ml.
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.
V intent to treat analizi (pomanjkanje podatkov in sprememba protiretrovirusne terapije se smatra kot neuspeh) je bil delež bolnikov s HIV- 1 RNA pod 400 kopij/ ml 80% in bolnikov z manj kot 50 kopijami/ ml 76% v 48. tednu zdravljenja z 245 mg tenofovirdizoproksilom (v obliki fumarata) v primerjavi z 84% in 80% v stavudinski skupini.
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.
V 144. tednu je bil delež bolnikov s HIV- 1 RNA pod 400 kopij/ ml 71% in bolnikov z manj kot 50 kopij/ ml 68% v skupini z 245 mg tenofovirdizoproksilom (v obliki fumarata) v primerjavi z 64% in 63% v stavudinski skupini.
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).
Srednja vrednost spremembe od začetne vrednosti za HIV- 1 RNA in število CD4 je bila v 48. tednu zdravljenja podobna v obeh zdravljenih skupinah (- 3, 09 log10 kopij/ ml, +169 celic/ mm3 pri 245 mg tenofovirdizoproksilu (v obliki fumarata) ter - 3, 09 log10 kopij/ ml, +167 celic/ mm3 pri stavudinski skupini).
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).
V 144. tednu zdravljenja je ostala srednja vrednost spremembe od začetne vrednosti podobna v obeh zdravljenih skupinah (- 3, 07 log10 kopij/ ml in +263 celic/ mm3 v skupini z 245 mg tenofovirdizoproksilom (v obliki fumarata) ter - 3, 03 log10 kopij/ ml in +283 celic/ mm3 v stavudinski skupini).
A consistent response to treatment with tenofovir disoproxil 245 mg (as fumarate) was seen regardless of baseline HIV-1 RNA and CD4 count.
Ne glede na začetno vrednost HIV- 1 RNA in števila CD4 je bil odziv na zdravljenje z 245 mg tenofovirdizoproksilom (v obliki fumarata) enak.
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%).
Mutacija K65R se je pojavila pri bolnikih v tenofovirdizoproksil fumaratni skupini v rahlo zvišanem odstotku kot pri aktivni kontrolni skupini (2, 7% napram 0, 7%).
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.
V skupini z 245 mg tenofovirdizoproksilom (v obliki fumarata) je imelo 8 bolnikov HIV, ki je izražal mutacijo K65R, pri 7 od teh se je ta pojavila v prvih 48 tednih zdravljenja, pri enem pa v 96. tednu.
Data pertaining to HBV:
Informacije, ki se nanašajo na virus HBV:
HBV antiviral activity in vitro:
Protivirusna aktivnost proti virusu HBV in vitro:
The in vitro antiviral activity of tenofovir against HBV was assessed in the HepG2 2.2.15 cell line.
Protivirusno aktivnost tenofovirja proti virusu HBV in vitro so ocenili na celični liniji HepG2 2. 2. 15.
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.
Vrednosti EC50 za tenofovir so bile v razponu od 0, 14 do 1, 5 µmol/ l, vrednosti CC50 (50% citotoksične koncentracije) pa so bile > 100 µmol/ l.
No HBV mutations associated with tenofovir disoproxil fumarate resistance have been identified (see Clinical results).
Mutacij virusa HBV, povezanih z rezistenco na tenofovirdizoproksil fumarat, niso odkrili (glejte razdelek Klinični rezultati).
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.
V celičnih preiskavah so bili sevi HBV z mutacijami rtV173L, rtL180M in rtM204I/ V, povezanimi z rezistenco na lamivudin in telbivudin, 0, 7 - do 3, 4- krat bolj občutljivi na tenofovir kot pri divjem tipu virusa.
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.
Sevi virusa HBV z mutacijami rtL180M, rtT184G, rtS202G/ I, rtM204V in rtM250V, povezanimi z rezistenco na entecavir, so bili 0, 6 - do 6, 9- krat bolj občutljivi na tenofovir kot pri divjem tipu virusa.
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.
Sevi virusa HBV z mutacijami rtA181V in rtN236T, povezanimi z rezistenco na adefovir, so bili 2, 9 - do 10- krat bolj občutljivi na tenofovir kot pri divjem tipu virusa.
Viruses containing the rtA181T mutation remained susceptible to tenofovir with EC50 values 1.5-fold that of wild-type virus.
Virusi z mutacijo rtA181T so ostali občutljivi za tenofovir, vrednosti EC50 pa so bile 1, 5- krat večje kot pri divjem tipu virusa.
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.
Dokaz uspešnosti tenofovirdizoproksil fumarata temelji na histoloških, viroloških, biokemijskih in seroloških odzivih zlasti pri še nezdravljenih odraslih, s kroničnim hepatitisom B, pozitivnim na HBeAg in negativnim na HBeAg s kompenzirano jetrno boleznijo.
Experience in patients with compensated liver disease:
14 Izkušnje pri bolnikih s kompenzirano jetrno boleznijo:
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.
Rezultati iz 48 tednov dveh randomiziranih dvojno slepih študij 3. faze, v katerih so primerjali tenofovirdizoproksil fumarat in adefovirdipivoksil pri bolnikih s kompenzirano jetrno boleznijo, so prikazani v preglednici 2 spodaj.
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.
V študiji GS- US- 174- 0103 je sodelovalo 266 (naključno razporejenih in zdravljenih) bolnikov, pozitivnih na HBeAg, v študiji GS- US- 174- 0102 pa je sodelovalo 375 (naključno razporejenih in zdravljenih) bolnikov, negativnih na HBeAg in pozitivnih na HBeAb.
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).
V obeh študijah je bil tenofovirdizoproksil fumarat pomembno učinkovitejši od adefovirdipivoksila v primarnem cilju učinkovitosti študije, popolnemu odzivu (opredeljeni kot ravni HBV DNA < 400 kopij/ ml in izboljšanju za vsaj 2 točki na Knodellovi nekroinflamatorni lestvici (Knodell Necroinflammatory Score) brez poslabšanja na Knodellovi fibrozni lestvici (Knodell Fibrosis)).
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.
Zdravljenje z 245 mg tenofovirdizoproksila (v obliki fumarata) je bilo povezano tudi s pomembno večjim deležem bolnikov z < 400 kopij/ ml HBV DNA, v primerjavi z zdravljenjem z 10 mg adefovirdipivoksila.
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).
Pri obeh zdravljenjih je bil v 48. tednu histološki odziv podoben (opredeljen kot izboljšanje za vsaj 2 točki na Knodellovi nekroinflamatorni lestvici brez poslabšanja na Knodellovi fibrozni lestvici (glejte preglednico 2 spodaj).
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).
V študiji GS- US- 174- 0103 je imel v 48. tednu pomembno večji delež bolnikov v skupini, ki je prejemala tenofovirdizoproksil fumarat, normalizirane ravni ALT in dosegel izgubo HBsAg, kot v skupini, ki je prejemala adefovirdipivoksil (glejte preglednico 2 spodaj).
Efficacy parameters in compensated HBeAg positive and HBeAg negative patients at week 48
Parametri učinkovitosti pri kompenziranih bolnikih, pozitivnih na HBeAg in negativnih na HBeAg, v 48. tednu
Study 174-0102 (HBeAg negative)
Študija 174- 0102 (negativni na
Study 174-0103 (HBeAg positive)
HBeAg)
Parameter
Študija 174- 0103 (pozitivni na
Tenofovir Adefovir dipivoxil
HBeAg)
Tenofovir Adefovir dipivoxil
Parameter
mg disoproxil 245 mg (as fumarate)
245 mg
n = 250
tenofovirdizoproksila (v obliki fumarata) n = 250
= 125 n = 176
adefovirdipivoksila tenofovirdizoproksila (v obliki fumarata) n = 125 n = 176
= 90
adefovirdipivoksila n = 90
Complete response (%)a Histology
Popolni odziv (%) a Histologija
Histological response (%)b
Histološki odziv (%) b
Median HBV DNA reduction from baselinec (log10 copies/ ml) HBV DNA (%)
Mediana zmanjšanja HBV DNA v primerjavi z izhodiščno točkoc (log10 kopij/ ml) HBV DNA (%)
< 400 copies/ ml (< 69 IU/ ml) ALT (%)
< 400 kopij/ ml (< 69 i. e. / ml) ALT (%)
Normalised ALTd Serology (%)
Normalizirana ALTd Serologija (%)
HBeAg loss/ seroconversion
Izguba/ serološka konverzija HBeAg
N/ A N/ A
Ni podatka
22/ 21
Ni podatka 22/ 21
HBsAg loss/ seroconversion
Izguba/ serološka konverzija HBsAg
* 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.
15 b izboljšanje za vsaj 2 točki na Knodellovi nekroinflamatorni lestvici brez poslabšanja na Knodellovi fibrozni lestvici, c Mediana sprememba HBV DNA v primerjavi z izhodiščno točko le odraža razliko med izhodiščno točko HBV DNA in mejo zaznavanja pri določanju vsebnosti, d V populaciji, ki so jo uporabili za analizo normalizacije ALT, so bili samo bolniki z ravnijo ALT nad ZMN v izhodiščni točki.
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.
Tenofovirdizoproksil fumarat je bil povezan s pomembno večjim deležem bolnikov z ravnmi HBV DNA, ki jih ni bilo mogoče zaznati (< 169 kopij/ ml [< 29 i. e. / ml]; meja kvantifikacije pri Roche Cobas Taqmanovem preskusu HBV), v primerjavi z adefovirdipivoksilom (študija GS- US- 174- 0102 91% v primerjavi s 56% in študija GS- US- 174- 0103 69% v primerjavi z 9%).
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.
Pri kombinaciji študij GS- US- 174- 0102 in GS- US- 174- 0103 je bil odziv na zdravljenje pri bolnikih, ki so bili zdravljeni z nukleozidi (n = 51), in bolniki, ki še niso bili zdravljeni z nukleozidi (n = 375), ter pri bolnikih z normalno ravnijo ALT (n = 21) in nenormalno ravnijo ALT (n = 405), ob izhodiščni točki, primerljiv.
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.
73% bolnikov, zdravljenih z nukleozidi, in 69% bolnikov, ki še niso bili zdravljeni z nukleozidi, je doseglo popoln odziv na zdravljenje; 90% bolnikov, ki še niso bili zdravljeni z nukleozidi, in 88% bolnikov, zdravljenih z nukleozidi, je doseglo supresijo HBV DNA < 400 kopij/ ml.
All patients with normal ALT at baseline and 88% of patients with abnormal ALT at baseline achieved HBV DNA suppression < 400 copies/ ml.
Supresijo HBV DNA < 400 kopij/ ml so dosegli vsi bolniki z normalno ravnijo ALT ob izhodiščni točki in 88% bolnikov z nenormalno ravnijo ALT ob izhodiščni točki.
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
V randomizirani, 48- tedenski dvojno slepi kontrolirani študiji z 245 mg tenofovirdizoproksila (v obliki fumarata) pri bolnikih s sočasno okužbo z virusom HIV- 1 in kroničnim hepatitisom B, ki so predhodno prejemali lamivudin (študija ACTG 5127), je bila pri bolnikih, ki so bili naključno razporejeni v skupino, ki je prejemala tenofovir, povprečna serumska koncentracija HBV DNA ob izhodiščni točki 9, 45 log10 kopij/ ml (n = 27).
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).
Pri bolnikih, za katere obstajajo podatki za 48 tednov, je bilo zdravljenje z 245 mg tenofovirdizoproksila (v obliki fumarata) povezano s povprečno spremembo koncentracije HBV DNA v serumu od izhodiščne točke - 5, 74 log10 kopij/ ml (n = 18).
Experience in patients with persistent viral replication:
Izkušnje pri bolnikih s persistirajočo replikacijo virusa:
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.
Učinkovitost in varnost 245 mg tenofovirdizoproksila (v obliki fumarata) ali 245 mg tenofovirdizoproksila (v obliki fumarata) in 200 mg emtricitabina vrednotijo v randomizirani, dvojno slepi študiji (študija GS- US- 174- 0106), pri bolnikih, pozitivnih na HBeAg in negativnih na HBeAg, s persistirajočo viremijo (HBV DNA ≥ 1. 000 kopij/ ml), med prejemanjem 10 mg adefovirdipivoksila več kot 24 tednov.
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).
Skupno je v 24. tednu zdravljenja z režimom, ki je vseboval tenofovir, 77% (46/ 60) bolnikov imelo HBV DNA < 400 kopij/ ml (< 69 i. e. / ml), 62% (37/ 60) bolnikov pa ravni HBV DNA, ki jih ni bilo mogoče zaznati (manj kot 169 kopij/ ml [< 29 i. e. / ml]; meja kvantifikacije pri Roche Cobas TaqManovem preskusu HBV).
In addition, at week 24, the percentage of patients who had normal ALT was 68% (42/ 62).
Poleg tega je bil odstotek bolnikov, ki so v 24. tednu imeli normalno raven ALT, 68% (42/ 62).
Clinical resistance:
Klinična rezistenca:
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.
Pri 426 bolnikih, negativnih na HBeAg (GS- US- 174- 0102, n = 250) in pozitivnih na HBeAg (GS- US- 174- 0103, n = 176), so ocenili genotipske spremembe HBV- polimeraze.
Genotypic evaluations were performed on all patients with HBV DNA > 400 copies/ ml at week 48.
Genotipsko oceno so opravili pri vseh bolnikih s HBV DNA > 400 kopij/ ml v 48. tednu.
No mutations associated with tenofovir disoproxil fumarate resistance have been identified.
Mutacij, ki bi bile povezane z rezistenco na tenofovirdizoproksil fumarat, niso odkrili.
Tenofovir disoproxil fumarate is a water soluble ester prodrug which is rapidly converted in vivo to tenofovir and formaldehyde.
Tenofovirdizoproksil fumarat je vodotopen ester, predzdravilo, ki se in vivo hitro pretvori v tenofovir in formaldehid.
Absorption Following oral administration of tenofovir disoproxil fumarate to HIV infected patients, tenofovir disoproxil fumarate is rapidly absorbed and converted to tenofovir.
Absorbcija Pri bolnikih, okuženih s HIV, se po peroralnem vnosu tenofovirdizoproksil fumarat hitro absorbira in pretvori v tenofovir.
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.
Po jemanju večkratnih odmerkov tenofovirdizoproksil fumarata s hrano pri bolnikih, okuženih s HIV, so bile srednje (% koeficienta variacije) vrednosti Cmax 326 (36, 6%) ng/ ml, AUC0- ∞ 3. 324 (41, 2%) ng· h/ ml in Cmin 64, 4 (39, 4%) ng/ ml tenofovirja.
Maximum tenofovir concentrations are observed in serum within one hour of dosing in the fasted state and within two hours when taken with food.
Najvišje koncentracije tenofovirja so opazne v serumu znotraj ene ure po zaužitju na tešče in znotraj dveh ur po zaužitju s
The oral bioavailability of tenofovir from tenofovir disoproxil fumarate in fasted patients was approximately 25%.
Peroralna biološka razpoložljivost tenofovirja iz tenofovirdizoproksil fumarata je bila približno 25% pri teščih bolnikih.
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%.
Jemanje tenofovirdizoproksil fumarata z z maščobami bogatim obrokom je povečalo peroralno biološko razpoložljivost s povečanjem AUC tenofovirja za približno 40% in Cmax za približno 14%.
Following the first dose of tenofovir disoproxil fumarate in fed patients, the median Cmax in serum ranged from 213 to 375 ng/ ml.
Po vnosu prvega odmerka tenofovirdizoproksil fumarata je vrednost mediane Cmax v serumu pri sitih bolnikih znašala od 213 do 375 ng/ ml.
However, administration of tenofovir disoproxil fumarate with a light meal did not have a significant effect on the pharmacokinetics of tenofovir.
Vendar pa jemanje tenofovirdizoproksil fumarata z lažjim obrokom ni imelo bistvenega vpliva na farmakokinetiko tenofovirja.
Distribution Following intravenous administration the steady-state volume of distribution of tenofovir was estimated to be approximately 800 ml/ kg.
Porazdelitev Po intravenoznem odmerku je volumen porazdelitve tenofovirja v stanju dinamičnega ravnotežja znašal po ocenah približno 800 ml/ kg.
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).
Po peroralnem vnosu tenofovirdizoproksil fumarata se tenofovir porazdeli po večini tkiv z najvišjo koncentracijo v ledvicah, jetrih in v vsebini črevesja (predklinične študije).
Biotransformation In vitro studies have determined that neither tenofovir disoproxil fumarate nor tenofovir are substrates for the CYP450 enzymes.
Biotransformacija In vitro študije so pokazale, da niti tenofovirdizoproksil fumarat niti tenofovir nista substrata za CYP450 encime.
Tenofovir disoproxil fumarate at a concentration of 100 µmol/ l had no
Poleg tega tenofovir in vitro pri koncentracijah, ki so bistveno višje (približno 300 krat) od koncentracij opaženih in vivo, ni zaviral presnavljanja zdravil, ki se biotransformirajo s katerokoli od pomembnejših izoform glavnega humanega CYP450 (CYP3A4, CYP2D6, CYP2C9, CYP2E1 ali CYP1A1/ 2).
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.
Tenofovirdizoproksil fumarat ni imel pri koncentraciji 100 µmol/ l nobenega vpliva na katerokoli obliko CYP450 izoformov, izjema je CYP1A1/ 2, kjer so opazili majhno (6%) toda statistično pomembno zmanjšanje presnove substrata za CYP1A1/ 2.
Based on these data, it is unlikely that clinically significant interactions involving tenofovir disoproxil fumarate and medicinal products metabolised by CYP450 would occur.
Na podlagi teh podatkov ni verjetno, da bi prišlo do klinično pomembnih interakcij med tenofovirdizoproksil fumaratom in zdravili, ki jih presnavlja CYP450.
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.
Izločanje Tenofovir se primarno izloča preko ledvic tako s filtracijo kot z aktivnim tubularnim transportnim sistemom, pri čemer se po intravenoznem vnosu približno 70- 80% odmerka izloči nespremenjenega s sečem.
Renal clearance has been estimated to be approximately 160 ml/ h/ kg (approximately 210 ml/ min), which is in excess of the glomerular filtration rate.
Ocenjeno je, da znaša skupni očistek približno 230 ml/ h/ kg (približno 300 ml/ min), ledvični očistek je približno 160 ml/ h/ kg (približno 210 ml/ min) kar presega nivo glomerularne filtracije.
Linearity/ non-linearity The pharmacokinetics of tenofovir were independent of tenofovir disoproxil fumarate dose over the dose range 75 to 600 mg and were not affected by repeated dosing at any dose level.
Tudi ponavljajoče jemanje tenofovirja, neodvisno od jakosti odmerka, ne vpliva na farmakokinetiko.