natgillin/translations-raw huggingface dataset:
Patients with HIV-1 expressing three or more thymidine analogue associated mutations (TAMs) that included either an M41L or an L210W substitution in RT showed reduced susceptibility to tenofovir disoproxil fumarate.
Bolniki, pri katerih je HIV- 1 izražal tri ali več mutacij povezanih z analogom timidina (TAM - thymidine - analogue associated mutations), ki so vsebovale mutacijo M41L ali L210W reverzne transkriptaze, so kazali zmanjšano občutljivost za zdravljenje s tenofovirdizoproksil fumaratom.
In vivo resistance (antiretroviral-naïve patients): extremely limited resistance data from patients treated with Atripla are currently available.
Podatkov o odpornosti pri bolnikih, ki jemljejo zdravilo Atripla, je trenutno zelo malo.
However, in a 144-week open-label randomised clinical study (GS-01-934) in antiretroviral-naïve patients, where efavirenz, emtricitabine and tenofovir disoproxil fumarate were used as individual formulations (or as efavirenz and the fixed combination of emtricitabine and tenofovir disoproxil fumarate (Truvada) from week 96 to 144), genotyping was performed on plasma HIV-1 isolates from all patients with confirmed HIV RNA > 400 copies/ ml at week 144 or early study drug discontinuation (see section on Clinical experience).
Vendar pa so v 144- tedenski odprti randomizirani klinični študiji (GS- 01- 934), v kateri so pri bolnikih, ki še niso bili zdravljeni s protiretrovirusnimi zdravili, uporabili efavirenz, emtricitabin in tenofovirdizoproksil fumarat v ločenih formulacijah (ali kot efavirenz in fiksna kombinacija emtricitabina in tenofovirdizoproksil fumarata (Truvada) od 96. do 144. tedna), opravili genotipizacijo izolatov virusa HIV- 1 iz plazme vseh bolnikov s potrjeno koncentracijo HIV RNA > 400 kopij/ ml v 144. tednu ali pri zgodnji prekinitvi jemanja študijskega zdravila (glejte poglavje Klinične izkušnje).
• The M184V/ I mutation developed in 2/ 19 (10.5%) isolates analysed from patients in the efavirenz + emtricitabine + tenofovir disoproxil fumarate group and in 10/ 29 (34.5%) isolates analysed from the efavirenz + lamivudine/ zidovudine group (p-value < 0.05, Fisher’ s Exact test comparing the emtricitabine + tenofovir disoproxil fumarate group to the lamivudine/ zidovudine group among all subjects). • No virus analysed contained the K65R mutation. • Genotypic resistance to efavirenz, predominantly the K103N mutation, developed in virus from 13/ 19 (68%) patients in the efavirenz + emtricitabine + tenofovir disoproxil fumarate group and in virus from 21/ 29 (72%) patients in the efavirenz + lamivudine/ zidovudine group.
• Mutacija M184V/ I se je pojavila pri 2 od 19 (10, 5%) analiziranih izolatih bolnikov v skupini, ki je prejemala efavirenz + emtricitabin + tenofovirdizoproksil fumarat, ter pri 10 od 29 (34, 5%) analiziranih izolatih skupine, ki je prejemala efavirenz + lamivudin/ zidovudin (vrednost p < 0, 05, Fisherjev test natančnosti na osnovi primerjave skupine emtricitabin+tenofovirdizoproksil fumarat s skupino lamivudin/ zidovudin med vsemi preiskovanci). • Noben analiziran virus ni vseboval mutacije K65R. • Genotipska rezistenca na efavirenz, pretežno mutacija K103N, se je pojavila pri virusih 13 od 19 (68%) bolnikov v skupini, ki je prejemala efavirenz + emtricitabin + tenofovirdizoproksil fumarat, ter pri virusih 21 od 29 (34, 5%) bolnikov v skupini, ki je prejemala efavirenz + lamivudin/ zidovudin.
A summary of resistance mutation development is shown in Table 5.
Povzetek pojava mutacij za razvoj odpornosti je prikazan v tabeli 5.
26 Table 5:
31 Tabela 5:
Development of resistance in study GS-01-934 through week 144
Razvoj odpornosti v študiji GS- 01- 934 do 144. tedna
Efavirenz+
efavirenz+
Efavirenz+lamivudine/
efavirenz+lamivudin/ zidovudin
emtricitabine+
emtricitabin+
Resistance analysis by On-therapy genotypes
tenofovirdizaproksil fumarat (N=244) Analiza odpornosti do 144. tedna
Efavirenz resistance
Zdravljeni genotipi Odpornost na efavirenz1
G190A/ S Y188C/ H V108I P225H
G109A/ S Y188C/ H V108I P225H
1 Other efavirenz resistance mutations included A98G (n=1), K103E (n=1), V179D (n=1), and M230L (n=1).
* p- vrednost < 0, 05, primerjava skupine, ki je prejemala efavirenz + emtricitabin + tenofovirdizoproksil fumarat s skupino, ki je prejemala efavirenz + lamivudin/ zidovudin pri vseh bolnikih s Fisherjevim testom natančnosti 1 Druge mutacije za odpornost na efavirenz so vključevale A98G (n=1), K103E (n=1), V179D (n=1) in M230L (n=1).
2 Thymidine analogue associated mutations included D67N (n=1) and K70R (n=1).
2 Mutacije povezane z analogom timidina (TAM = thymidine- analogue associated mutations), vključno z D67N (n=1) in K70R (n=1).
In a 144-week open-label randomised clinical study (GS-01-934) antiretroviral treatment-naïve HIV-1 infected patients received either a once-daily regimen of efavirenz, emtricitabine and tenofovir disoproxil fumarate or a fixed combination of lamivudine and zidovudine (Combivir) administered twice daily and efavirenz once daily (please refer to the Summary of Product Characteristics for Truvada).
V 144- tedenski odprti randomizirani klinični študiji (GS- 01- 934) so bolniki, okuženi z virusom HIV- 1, ki še niso prejemali protiretrovirusnega zdravljenja, prejemali bodisi efavirenz, emtricitabin in tenofovirdizoproksil fumarat enkrat na dan bodisi fiksno kombinacijo lamivudina in zidovudina (Combivir) dvakrat na dan ter efavirenz enkrat na dan (prosimo, glejte Povzetek glavnih značilnosti zravila Truvada).
Patients who completed 144 weeks of treatment with either treatment arm in study GS-01-934 were given the option to continue in an open-label extended phase of the study with Atripla on an empty stomach.
Bolnikom, ki so končali 144- tedensko zdravljenje v eni od obeh skupin v študiji GS- 01- 934, so ponudili možnost udeležbe v odprti podaljšani fazi študije z zdravilom Atripla, jemanim na tešče.
Preliminary 24-week data are available from a total of 286 patients who changed to Atripla:
Preliminarni podatki po 24 tednih so na voljo za skupaj 286 bolnikov, ki so prešli na zdravilo Atripla:
160 had previously received efavirenz, emtricitabine and tenofovir disoproxil fumarate, and 126 had previously received Combivir and efavirenz.
160 jih je predhodno prejemalo efavirenz, emtricitabin in tenofovirdizoproksil fumarat, 126 pa Combivir in efavirenz.
The majority of patients from both initial treatment groups maintained virologic suppression after changing to Atripla.
Po prehodu na zdravilo Atripla se je virološka supresija ohranila pri večini bolnikov iz obeh prvotnih skupin.
In 91% of the patients the HIV-1 RNA plasma concentrations remained < 50 copies/ ml and in 97% < 400 copies/ ml, after 24 weeks of Atripla treatment (intention to treat analysis (ITT), missing=failure).
Po 24 tednih zdravljenja z zdravilom Atripla se je pri 91% bolnikov plazemska koncentracija HIV- 1 RNA ohranila < 50 kopij/ ml, pri 97% bolnikov pa < 400 kopij/ ml (analiza z namenom zdravljenja (analiza ITT), nepopoln = neuspešen).
Study AI266073 was a 48-week open-label randomised clinical study in HIV infected patients comparing the efficacy of Atripla to antiretroviral therapy consisting of at least two nucleoside or nucleotide reverse transcriptase inhibitors (NRTIs) with a protease inhibitor or non-nucleoside reverse transcriptase inhibitor; however not a regimen containing all Atripla components (efavirenz, emtricitabine and tenofovir disoproxil fumarate).
Pri bolnikih, okuženih z virusom HIV, je bila izvedena 48- tedenska odprta randomizirana klinična študija AI266073, v kateri so učinkovitost zdravila Atripla primerjali z učinkovitostjo protiretrovirusnega zdravljenja z vsaj dvema nukleozidnima ali nukleotidnima zaviralcema reverzne transkriptaze (NRTI) z zaviralcem proteaze ali nenukleozidnim zaviralcem reverzne transkriptaze, vendar pa ne z režimom, ki bi vključeval vse tri učinkovine zdravila Atripla (efavirenz, emtricitabin in tenofovirdizoproksil fumarat).
Atripla was administered on an empty stomach (see section 4.2).
Zdravilo Atripla so bolniki jemali na tešče (glejte poglavje 4. 2).
Patients had never experienced virological failure on a previous antiretroviral therapy, had no known HIV-1 mutations that confer resistance to any of the three components within Atripla, and had been virologically suppressed for at least three months at baseline.
Pri bolnikih ni pri nobenem predhodnem 32 protiretrovirusnem zdravljenju prišlo do virološke odpovedi.
Patients either changed to Atripla (N=203) or continued on their original antiretroviral treatment regimen (N=97).
Bolniki niso imeli nobenih znanih mutacij HIV- 1, odgovornih za odpornost na katero od treh učinkovin zdravila Atripla in so imeli na začetku vsaj tri mesece virusno supresijo.
Forty-eight
Bolniki so zamenjali zdravljenje in začeli prejemati zdravilo Atripla (N=203) ali pa so nadaljevali prvotno protiretrovirusno zdravljenje (N = 97).
27 week data showed that high levels of virologic suppression, comparable to the original treatment regimen, were maintained in patients who were randomised to change to Atripla (see Table 6).
Po 48 tednih so podatki pri bolnikih, ki so jih naključno razporedili v skupino, ki je prejemala zdravilo Atripla, pokazali, da se je ohranila visoka stopnja virološke supresije, primerljiva s prvotnim zdravljenjem (glejte tabelo 6).
48-week efficacy data from study AI266073 in which Atripla was administered to virologically suppressed patients on combination antiretroviral therapy
Podatki učinkovitosti po 48 tednih iz študije AI266073, v kateri so zdravilo Atripla dajali bolnikom z virološko supresijo, ki so prejemali kombinirano protiretrovirusno zdravljenje
Treatment group
Končni opazovani
Endpoint
(N = 203)
Atripla (N=203) n/ N (%)
(N = 97)
Stayed on original treatment regimen
prvotnim zdravljenjem
Difference between Atripla and original treatment regimen
dogodek
(95%CI)
n/ N (%)
patients with HIV-1 RNA < 50 copies/ ml PVR (KM)
bolniki s HIV- 1 RNA < 50 kopij/ ml PVR (KM)
8.9% (-7.7% to 25.6%)
8, 9% (- 7, 7% do 25, 6%)
M=Excluded M=Failure
M = izključeno M = neuspeh
85/ 87 (97.7%) 85/ 97 (87.6%)
85/ 87 (97, 7%) 85/ 97 (87, 6%)
1.2% (-2.3% to 6.7%) 0.5% (-7.0% to 9.3%)
1, 2% (- 2, 3% do 6, 7%) 0, 5% (- 7, 0% do 9, 3%)
-3.3% (-8.3% to 2.7%)
- 3, 3% (- 8, 3% do 2, 7%)
patients with HIV-1 RNA < 200 copies/ ml PVR (KM)
bolniki s HIV- 1 RNA < 200 kopij/ ml PVR (KM)
-0.5% (-3.2% to 2.2%)
- 0, 5% (- 3, 2% do 2, 2%)
0% (-2.4% to 4.2%)
0% (- 2, 4% do 4, 2%)
-0.5% (-7.6% to 7.9%)
- 0, 5% (- 7, 6% do 7, 9%)
PVR (KM):
PVR( KM): čisti virološki odziv, ocenjen po metodi Kaplan Meier (KM).
Pure virologic response assessed using the Kaplan Meier (KM) method M:
M: manjkajoči.
Missing Modified LOCF:
Prilagojeni LOCF:
Post-hoc analysis where patients who failed virologically or discontinued for adverse events were treated as failures; for other drop-outs, the LOCF (last observation carried forward) method was applied
Post- hoc analiza pri kateri so bili bolniki z virusnim neodzivom in bolniki pri katerih je bilo zdravljenje prekinjeno zaradi pojava neželenih učinkov obravnavani kot neuspeh; pri ostalih izključenih bolnikih pa je bila uporabljena metoda LOCF (last observation carried forward).
When the two strata were analysed separately, response rates in the stratum with prior PI-treatment were numerically lower for patients switched to Atripla [92.4% versus 94.0% for the PVR (sensitivity analysis) for Atripla and SBR patients respectively; a difference (95%CI) of -1.6% (-10.0%, 6.7%)].
Pri ločeni analizi dveh skupin je bil delež odziva v skupini s predhodnim zdravljenjem z zaviralci proteaz (ZP) numerično nižji pri bolnikih, ki so prešli na zdravljenje z zdravilom Atripla [vrednost PVR (analiza senzitivnosti) 92, 4% pri bolnikih, ki so prejemali zdravilo Atripla v primerjavi z 94, 0% pri SBR bolnikih; razlika (95% interval zaupanja) - 1, 6% (- 10, 0%, 6, 7%)].
In the prior-NNRTI stratum, response rates were 98.9% vs 97.4% for Atripla and SBR patients respectively; a difference (95%CI) of 1.4% (-4.0%, 6.9%).
V skupini s predhodnim NNRTI zdravljenjem je bil delež odziva pri uporabi zdravila Atripla 98, 9%, pri SBR bolnikih pa 97, 4%; razlika (95% interval zaupanja) 1, 4% (- 4, 0%, 6, 9%)].
Patients coinfected with HIV and HBV: limited clinical experience in patients co-infected with HIV and HBV suggests that treatment with emtricitabine or tenofovir disoproxil fumarate in antiretroviral combination therapy to control HIV infection also results in a reduction in HBV DNA (3 log10 reduction or 4 to 5 log10 reduction, respectively) (see section 4.4).
Bolniki, sočasno okuženi z virusoma HIV in HBV: omejene klinične izkušnje pri bolnikih, ki so hkrati okuženi z virusoma HIV in HBV, kažejo, da se zdravljenje z emtricitabinom ali tenofovirdizoproksil fumaratom v kombiniranem protiretrovirusnem zdravljenju za nadzorovanje okužbe z virusom HIV izraža
The separate pharmaceutical forms of efavirenz, emtricitabine and tenofovir disoproxil fumarate were used to determine the pharmacokinetics of efavirenz, emtricitabine and tenofovir disoproxil fumarate, administered separately in HIV infected patients.
Za določanje farmakokinetičnih lastnosti efavirenza, emtricitabina in tenofovirdizoproksil fumarata so bile uporabljene ločene farmacevtske oblike efavirenza, emtricitabina in tenofovirdizoproksil fumarata, ki so bile pri bolnikih, okuženih z virusom HIV, uporabljene posebej.
The bioequivalence of one Atripla film-coated tablet with one efavirenz 600 mg film-coated tablet plus one emtricitabine 200 mg hard capsule plus one tenofovir disoproxil 245 mg film-coated tablet (equivalent to 300 mg tenofovir disoproxil fumarate) administered together, was established following single dose administration to fasting healthy subjects in study GS-US-177-0105 (see Table 7).
Bioekvivalenco ene filmsko obložene tablete zdravila Atripla in skupaj uporabljenih ene 600- miligramske filmsko obložene tablete efavirenza, ene 200- miligramske trde kapsule emtricitabina ter ene 245- miligramske filmsko obložene tablete tenofovirdizoproksila (kar ustreza 300 mg tenofovirdizoproksil fumarata) so določili po uporabi enkratnega odmerka na tešče pri zdravih osebah v študiji GS- US- 177- 0105 (glejte tabelo 7).
28 Table 7:
Tabela 7:
Summary of pharmacokinetic data from study GS-US-177-0105
Povzetek farmakokinetičnih podatkov iz študije GS- US- 177- 0105
Tenofovir disoproxil
efavirenz (n = 45)
Efavirenz (n=45)
emtricitabin (n = 45)
GMR (%)
(%) (90 -
Emtricitabine (n=45) GMR (%)
GMR (%) (90 -
fumarate (n=45) GMR (%)
GMR (%) (90 -
Parameters
parametri
Test
test
Reference (90%CI) Test 98.79
IZ) test 98, 79
Reference (90%CI) Test Reference (90%CI) 88.84
referenca IZ) test referenca 88, 84
91.46
IZ) 91, 46
2,264.3
2. 264, 3
2,308.6
2. 308, 6
2,130.6
2. 130, 6
2,384.4
2. 384, 4
352.9
352, 9 (29, 6)
98.83) 99.29
AUC0- konec 125. 623, 6 132. 795, 7
AUC0-last
(90, 73,
(90.73,
10. 682, 6
10,682.6 10,874.4
10. 874, 4
1,948.8
1. 948, 8
1,969.0
1. 969, 0
(ng·h/ ml)
(27, 0) (ng· h/ ml) (25, 7)
(25.7) (27.0)
101, 23 95, 87
AUCinf
146. 074, 9 155. 518, 6 AUCinf
146,074.9 155,518.6
10. 854, 9
(89.63,
11. 054, 3
10,854.9 11,054.3
2. 314, 0
(94.86,
2. 319, 4
(ng·h/ ml)
(33, 1) (34, 6) (ng· h/ ml)
(33.1) (34.6)
(17, 9)
102.55)
(14, 9)
T1/ 2 (h)
180, 6 182, 5 T1/ 2
180.6 182.5 (45.3) (38.3)
(h) (45, 3) (38, 3)
Reference: single dose of a 600 mg efavirenz tablet, 200 mg emtricitabine capsule and 300 mg tenofovir disoproxil fumarate tablet taken under fasted conditions.
Reference: enkratni odmerek v obliki 600- miligramske tablete efavirenza, 200- miligramske kapsule emtricitabina in 300- miligramske tablete tenofovirdizoproksil fumarata, zaužit na tešče.
Absorption: in HIV infected patients, peak efavirenz plasma concentrations were attained by 5 hours and steady-state concentrations reached in 6 to 7 days.
Absorpcija: pri bolnikih, okuženih z virusom HIV, so bile največje koncentracije efavirenza v plazmi dosežene v 5 urah, dinamično ravnovesje koncentracije pa v 6 do 7 dneh.
In 35 patients receiving efavirenz 600 mg once daily, steady-state peak concentration (Cmax) was 12.9 ± 3.7 µM (29%) [mean ± standard deviation (S. D.) (coefficient of variation (%CV))], steady-state Cmin was 5.6 ± 3.2 µM (57%), and AUC was 184 ± 73 µM• h (40%).
V.))], Cmin 5, 6 ± 3, 2 µM (57%) in AUC 184 ± 73 µM• h (40%).
Following multiple dose oral administration of emtricitabine to 20 HIV infected patients, steady-state Cmax was 1.8 ± 0.7 µg/ ml (mean ± S. D.) (39%CV), steady-state Cmin was 0.09 ± 0.07 µg/ ml (80%) and the AUC was 10.0 ± 3.1 µg• h/ ml (31%) over a 24 hour dosing interval.
D.) (39% CV), Cmin v stanju dinamičnega ravnovesja 0, 09 ± 0, 07 µg/ ml (80%) in AUC 10, 0 ± 3, 1 µg• h/ ml (31%).
Following oral administration of a single 300 mg dose of tenofovir disoproxil fumarate to HIV-1 infected patients in the fasted state, maximum tenofovir concentrations were achieved within one hour and the Cmax and AUC (mean ± S. D.) (%CV) values were 296 ± 90 ng/ ml (30%) and 2,287 ± 685 ng• h/ ml (30%), respectively.
D.) (% CV) pa 2287 ± 685 ng• h/ ml (30%).
The oral bioavailability of tenofovir from tenofovir disoproxil fumarate in fasted patients was approximately 25%.
Peroralna biološka uporabnost tenofovirja iz tenofovirdizoproksil fumarata pri teščih bolnikih je bila približno 25%.
Atripla has not been evaluated in the presence of food.
Vpliv hrane: zdravila Atripla v prisotnosti hrane niso ocenjevali.
Administration of efavirenz capsules with a high fat meal increased the mean AUC and Cmax of efavirenz by 28% and 79%, respectively, compared to administration in a fasted state.
Uporaba kapsul efavirenza ob obroku z veliko količino maščob je povečala vrednost AUC za 28%, vrednost Cmax pa za 79%, v primerjavi z uporabo na tešče.
Compared to fasted administration, dosing of tenofovir disoproxil fumarate and emtricitabine in combination with either a high fat meal or a light meal increased the mean AUC and Cmax of tenofovir by 35% and 15%, respectively without affecting emtricitabine exposures.
V primerjavi z uporabo na tešče je odmerjanje tenofovirdizoproksil fumarata in emtricitabina v kombinaciji z obrokom z veliko količino maščob ali z lahkim obrokom povečala povprečno vrednost AUC tenofovirja za 35%, vrednost Cmax tenofovirja pa za 15%, pri tem pa se izpostavljenost emtricitabinu ni spremenila.
Atripla is recommended for administration on an empty stomach since food may increase efavirenz exposure and may lead to an increase in the frequency of adverse reactions (see sections 4.4 and 4.8).
Zdravilo Atripla je priporočljivo jemati na prazen želodec, saj lahko hrana poveča izpostavljenost efavirenzu, kar lahko poveča pogostnost neželenih učinkov (glejte poglavji 4. 4 in 4. 8).
It is anticipated that tenofovir exposure will be approximately 35% lower following administration of Atripla on an empty stomach as compared to the individual component tenofovir disoproxil fumarate when taken with food.
Po zaužitju zdravila Atripla na prazen želodec je pričakovana izpostavljenost tenofovirju približno za 35% manjša kot pri uporabi samega tenofovirdizoproksil fumarata s hrano.
Forty-eight week data from a clinical study (AI266073) showed maintenance of virologic suppression for patients who had stable virologic suppression on combination
Podatki po oseminštiridesetih tednih iz klinične študije (AI266073) so pokazali ohranjanje virološke supresije pri bolnikih s stabilno virološko supresijo pri kombiniranem protiretrovirusnem zdravljenju, ki so prešli na zdravljenje z zdravilom Atripla ob priporočilu, naj zdravilo Atripla jemljejo na prazen želodec.
Distribution: efavirenz is highly bound (> 99%) to human plasma proteins, predominantly albumin.
Porazdelitev: efavirenz se močno (> 99%) veže na človeške plazemske beljakovine, predvsem na albumin.
In vitro binding of emtricitabine to human plasma proteins is < 4% and independent of concentrations over the range of 0.02 to 200 µg/ ml.
In vitro je bila vezava emtricitabina na človeške plazemske beljakovine < 4% in neodvisna od koncentracije v razponu med 0, 02 in 200 µg/ ml.
Following intravenous administration the volume of distribution of emtricitabine was approximately 1.4 l/ kg.
Po intravenskem odmerku je volumen porazdelitve emtricitabina znašal približno 1, 4 l/ kg.
The mean plasma to blood concentration ratio was approximately 1.0 and the mean semen to plasma concentration ratio was approximately 4.0.
Povprečje razmerja koncentracije v plazmi in krvi je bilo približno 1, 0, razmerje koncentracije v spermi in plazmi pa približno 4, 0.
In vitro binding of tenofovir to human plasma or serum protein is < 0.7% and 7.2%, respectively over the tenofovir concentration range 0.01 to 25 µg/ ml.
V območju koncentracij tenofovirja od 0, 01 do 25 µg/ ml je vezava tenofovirja na človeške beljakovine v plazmi in vitro < 0, 7%, na serumske beljakovine pa 7, 2%.
Following intravenous administration the volume of distribution of tenofovir was approximately 800 ml/ kg.
Po intravenskem odmerku je volumen porazdelitve tenofovirja znašal približno 800 ml/ kg.
Biotransformation: studies in humans and in vitro studies using human liver microsomes have demonstrated that efavirenz is principally metabolised by the cytochrome P450 system to hydroxylated metabolites with subsequent glucuronidation of these hydroxylated metabolites.
Presnova: študije pri ljudeh in študije in vitro z uporabo človeških jetrnih mikrosomov so pokazale, da se efavirenz presnavlja predvsem s sistemom citokroma P450, in sicer v hidroksilirane presnovke, z nadaljnjo glukuronidacijo teh hidroksiliranih presnovkov.
These metabolites are essentially inactive against HIV-1.
Ti presnovki so večinoma neaktivni proti virusu HIV- 1.
The in vitro studies suggest that CYP3A4 and CYP2B6 are the major isoenzymes responsible for efavirenz metabolism and that it inhibits P450 isoenzymes 2C9, 2C19, and 3A4.
Raziskave in vitro kažejo, da sta CYP3A4 in CYP2B6 glavna izoencima, odgovorna za presnovo efavirenza, ter da zavirata izoencime P450 2C9, 2C19 in 3A4.
In in vitro studies efavirenz did not inhibit CYP2E1 and inhibited CYP2D6 and CYP1A2 only at concentrations well above those achieved clinically.
V raziskavah in vitro efavirenz ni zaviral izoencima CYP2E1, izoencima CYP2D6 in CYP1A2 pa je zaviral šele pri koncentracijah, ki so bile precej večje od tistih, ki jih dosežemo pri klinični uporabi zdravila.
Efavirenz plasma exposure may be increased in patients with homozygous G516T genetic variant of the CYP2B6 isoenzyme.
Plazemska izpostavljenost efavirenzu je lahko povečana pri bolnikih s homozigotno genetsko različico G516T izoencima CYP2B6.
Efavirenz has been shown to induce P450 enzymes, resulting in the induction of its own metabolism.
Pokazalo se je, da efavirenz inducira encime iz skupine citokromov P450, s čimer povzroči indukcijo svoje lastne presnove.
In uninfected volunteers, multiple doses of 200 to 400 mg per day for 10 days resulted in a lower than predicted extent of accumulation (22 to 42% lower) and a shorter terminal half-life of 40 to 55 hours (single dose half-life 52 to 76 hours).
Pri neokuženih prostovoljcih so 10- dnevni večkratni odmerki 200- 400 mg dnevno povzročili manjšo akumulacijo zdravila od pričakovane (22- 42% manjšo) in krajši končni razpolovni čas 40- 55 ur (razpolovni čas enkratnega odmerka je 52- 76 ur).
There is limited metabolism of emtricitabine.
35 Presnova emtricitabina poteka v manjšem obsegu.
The biotransformation of emtricitabine includes oxidation of the thiol moiety to form the 3'-sulphoxide diastereomers (approximately 9% of dose) and conjugation with glucuronic acid to form 2'-O-glucuronide (approximately 4% of dose).
Biotransformacija emtricitabina vključuje oksidacijo tiolne skupine, pri čemer nastanejo diastereomeri 3 '- sulfoksida (približno 9% odmerka), in konjugacijo z glukuronsko kislino, pri čemer nastane 2' - O- glukuronid (približno 4% odmerka).
In vitro studies have determined that neither tenofovir disoproxil fumarate nor tenofovir are substrates for the CYP450 enzymes.
Študije in vitro so pokazale, da tenofovirdizoproksil fumarat in tenofovir nista substrata za encime CYP450.