natgillin/translations-raw huggingface dataset:
I en 144- ugers open- label, randomiseret, klinisk undersøgelse (GS- 01- 934) med antiretroviral- naive patienter, hvor efavirenz, emtricitabin og tenofovirdisoproxilfumarat blev anvendt som individuel formulering (eller som efavirenz og en fast kombination af emtricitabin og tenofovirdisoproxilfumarat (Truvada) fra uge 96 til 144), er der imidlertid foretaget genotypebestemmelser på plasma- HIV- 1- isolater fra alle patienter med bekræftet HIV RNA > 400 kopier/ ml i uge 144 eller tidlig seponering (se afsnittet om Klinisk erfaring).
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).
• M184V/ I- mutationen udviklede sig hos 2/ 19 (10, 5%) af de isolater, der blev analyseret fra patienter i efavirenz + emtricitabin + tenofovirdisoproxilfumarat- gruppen og hos 10/ 29 (34, 5%) af de isolater, der blev analyseret fra efavirenz + lamivudin/ zidovudin- gruppen (p- værdi < 0, 05; Fishers eksakte test, som sammenligner alle patienterne fra henholdsvis emtricitabin + tenofovirdisoproxilfumarat- gruppen med lamivudin/ zidovudin- gruppen). • Ingen analyseret virus indeholdt K65R- mutationen. • Genotypisk resistens over for efavirenz, overvejende K103N- mutationen, udviklede sig i virus fra 13/ 19 (68%) af patienterne i efavirenz + emtricitabin + tenofovirdisoproxilfumarat- gruppen og i virus fra 21/ 29 (72%) af patienterne i efavirenz + lamivudin/ zidovudin- gruppen.
• 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.
Et resumé over udviklingen af resistensmutation findes i tabel 5.
A summary of resistance mutation development is shown in Table 5.
28 Tabel 5:
26 Table 5:
Resistensudvikling i undersøgelsen GS- 01- 934 til og med uge 144
Development of resistance in study GS-01-934 through week 144
Efavirenz+
Efavirenz+
Efavirenz+
Efavirenz+lamivudine/
emtricitabin+
emtricitabine+
lamivudin/ zidovudin
zidovudine
tenofovirdisoproxil - fumarat (N=244)
tenofovir disoproxil fumarate (N=244)
(N=243)
(N=243)
Resistensanalyse i uge 144
week 144 1
19
19 19 (100%)
31
31 (100%)
Behandlingsgenotyper Efavirenzresistens1
Efavirenz resistance
19 (100%) 13 (68%)
13 (68%)
29 21
21
(100%) (72%)
(72%)
K103N K101E
K103N K101E
(42%) (16%)
(42%) (16%)
18 * 3
18* 3
(62%) (10%)
(62%) (10%)
TAMs2
TAMs
* p- værdi < 0, 05, Fishers eksakte test, som sammenligner efavirenz + emtricitabin + tenofovirdisoproxilfumarat- gruppen med efavirenz + lamivudin/ zidovudin- gruppen blandt alle patienter.
* p-value < 0.05, Fisher’ s Exact test comparing efavirenz + emtricitabine + tenofovir disoproxil fumarate group to efavirenz + lamivudine/ zidovudine group among all patients.
2 Thymidin- analogassocierede mutationer omfattede D67N (n=1) og K70R (n=1).
2 Thymidine analogue associated mutations included D67N (n=1) and K70R (n=1).
For yderligere information se produktresuméerne for de individuelle komponenter med henblik på in vivo- resistens i forbindelse med disse lægemidler.
Please refer to the Summary of Product Characteristics for the individual components for additional information regarding in vivo resistance with these medicinal products.
I en 144- ugers open- label, randomiseret, klinisk undersøgelse (GS- 01- 934), hvor antiretroviralt - behandlingsnaive HIV- 1- inficerede patienter enten fik et efavirenzregime en gang dagligt, emtricitabin og tenofovirdisoproxilfumarat eller en fast kombination af lamivudin og zidovudin (Combivir), som blev givet to gange dagligt og efavirenz en gang dagligt (se produktresuméet for Truvada).
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).
Patienter, som fuldførte 144 ugers behandling med enten den ene eller den anden af behandlingsarmene i GS- 01- 934, fik mulighed for at fortsætte i en, forlænget open- label fase af undersøgelsen med Atripla på tom mave.
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.
Præliminære 24- ugers- data er tilgængelige fra 286 patienter, som skiftede til Atripla:
Preliminary 24-week data are available from a total of 286 patients who changed to Atripla:
160 havde tidligere fået efavirenz, emtricitabin og tenofovirdisoproxilfumarat, og 126 havde tidligere fået Combivir og efavirenz.
160 had previously received efavirenz, emtricitabine and tenofovir disoproxil fumarate, and 126 had previously received Combivir and efavirenz.
Størstedelen af patienterne fra begge initiale behandlingsgrupper opretholdt virologisk suppression efter skift til Atripla.
The majority of patients from both initial treatment groups maintained virologic suppression after changing to Atripla.
Hos 91% af patienterne forblev HIV- 1- RNA plasmakoncentrationerne < 50 kopier/ ml og hos 97% < 400 kopier/ ml efter 24 ugers behandling med Atripla (intention to treat- analyse (ITT), missing = failure).
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).
Undersøgelsen sammenligner Atriplas effekt med antiretroviral behandling bestående af mindst to nukleosid - eller nukleotid- revers transkriptase- hæmmere (NRTIere) i kombination med en proteasehæmmer eller en non- nukleosid- revers transkriptase- hæmmer; dog ikke en behandling, der indeholder alle Atripla- komponenterne (efavirenz, emtricitabin og
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).
Patienterne have aldrig oplevet virologisk svigt i forbindelse med tidligere antiretroviral behandling, havde ingen kendte HIV- 1- mutationer, som giver resistens over for en eller flere af komponenterne i Atripla og havde været virologisk supprimeret i mindst tre måneder ved baseline.
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.
Patienterne blev enten skiftet til Atripla (n=203) eller fortsatte med deres oprindelige antiretrovirale behandlingsregime (n=97).
Forty-eight
48- ugers- data viste, at høje niveauer af virologisk suppression, som var sammenlignelige med det oprindelige behandlingsregime, blev opretholdt hos patienter, som blev randomiseret til at skifte til Atripla (se tabel 6).
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).
48- ugers effektdata fra undersøgelse AI266073, hvor Atripla blev administreret til virologisk supprimerede patienter i antiretroviral kombinationsbehandling.
48-week efficacy data from study AI266073 in which Atripla was administered to virologically suppressed patients on combination antiretroviral therapy
Endpoint
Endpoint
Atripla (N=203)
Atripla (N=203) n/ N (%)
Blev i originalt
Stayed on original treatment regimen
Forskel mellem Atripla og
Difference between Atripla and original treatment regimen
behandlingsregime (95% CI)
(95%CI)
Patienter med HIV- 1 RNA < 50 kopier/ ml PVR (KM)
patients with HIV-1 RNA < 50 copies/ ml PVR (KM)
85, 5%
85.5%
8, 9% (- 7, 7% til 25, 6%)
8.9% (-7.7% to 25.6%)
M=Ekskluderede M=Failure Modificeret LOCF
M=Excluded M=Failure
179/ 181 (98, 9%) 179/ 203 (88, 2%) 190/ 203 (93, 6%)
179/ 181 (98.9%) 179/ 203 (88.2%)
85/ 87 (97, 7%) 85/ 97 (87, 6%) 94/ 97 (96, 9%)
85/ 87 (97.7%) 85/ 97 (87.6%)
1, 2% (- 2, 3% til 6, 7%) 0, 5% (- 7, 0% til 9, 3%) - 3, 3% (- 8, 3% til 2, 7%)
1.2% (-2.3% to 6.7%) 0.5% (-7.0% to 9.3%)
Patienter med HIV- 1 RNA < 200 kopier/ ml PVR (KM)
patients with HIV-1 RNA < 200 copies/ ml PVR (KM)
- 0, 5% (- 3, 2% til 2, 2%)
-0.5% (-3.2% to 2.2%)
0% (- 2, 4% til 4, 2%)
0% (-2.4% to 4.2%)
M=Failure
M=Failure
- 0, 5% (- 7, 6% til 7, 9%)
-0.5% (-7.6% to 7.9%)
Rent virologisk respons vurderet ved hjælp af Kaplan Meier (KM) metoden M:
Pure virologic response assessed using the Kaplan Meier (KM) method M:
Mangler Modificeret LOCF:
Missing Modified LOCF:
Post- hoc- analyse, hvor patienterne med virologisk "failure" eller som afsluttede p. g. a. bivirkninger, blev behandlet som "failures"; for andre "drop- outs" blev LOCF- metoden (last observation carried forward) brugt.
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
Når de to strata blev analyseret separat, var responsraterne i det stratum med tidligere proteasehæmmer- behandling numerisk lavere for de patienter, der skiftede til Atripla [92, 4% versus 94, 0% for PVR (sensitivitetsanalyse) for henholdsvis Atripla - og SBR- patienter (SBR, stayed on their baseline regimen); en forskel (95% CI) på - 1, 6% (- 10, 0%; 6, 7%)].
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%)].
I før- NNRTI- stratummet var responsraten 98, 9% versus 97, 4% for henholdsvis Atripla - og SBR- patienterne; en forskel (95% CI) på 1, 4% (- 4, 0%; 6, 9%).
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%).
Der er p. t. ingen tilgængelige data fra kliniske undersøgelser med Atripla til behandlingsnaive patienter eller til patienter, der tidligere har været i massiv behandling.
No data are currently available from clinical studies with Atripla in treatment-naïve patients or in heavily pretreated patients.
Der er ingen klinisk erfaring med Atripla til patienter, som har oplevet virologisk svigt i et first- line antiretroviralt regime eller i kombination med andre antiretrovirale lægemidler.
There is no clinical experience with Atripla in patients who are experiencing virological failure in a first-line antiretroviral treatment regimen or in combination with other antiretroviral agents.
Begrænset klinisk erfaring hos patienter, der samtidigt er inficerede med HIV og HBV, tyder på, at behandling med emtricitabin eller tenofovirdisoproxilfumarat i antiretroviral kombinationsbehandling til kontrol af HIV- infektion også resulterer i reduktion af HBV- DNA (henholdsvis 3 log10 reduktion eller 4- 5 log10 reduktion) (se pkt.
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).
De separate farmaceutiske former af efavirenz, emtricitabin og tenofovirdisoproxilfumarat blev anvendt til at bestemme farmakokinetikken af efavirenz, emtricitabin og tenofovirdisoproxilfumarat, når disse blev givet separat til HIV- inficerede patienter.
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.
Bioækvalensen af en filmovertrukken Atripla - tablet sammen med en 600 mg filmovertrukken efavirenz- tablet plus en 200 mg hård kapsel emtricitabin plus en 245 mg filmovertrukken tenofovirdisoproxil- tablet (svarende til 300 mg tenofovirdisoproxilfumarat) administreret samtidigt blev etableret efter administration af en enkelt dosis til raske fastende deltagere i undersøgelse GS- US- 177- 0105 (se tabel 7).
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).
Tabel 7:
28 Table 7:
Oversigt over farmakokinetiske data fra undersøgelse GS- US- 177- 0105
Summary of pharmacokinetic data from study GS-US-177-0105
Efavirenz (n=45)
Tenofovir disoproxil
Emtricitabin (n=45)
Efavirenz (n=45)
GMR
GMR (%)
Tenofovirdisoproxilfumarat (n=45)
Emtricitabine (n=45) GMR (%)
Reference (90% CI) Test Reference (90% CI) Test 98, 79 88, 84
Reference (90%CI) Test 98.79
Reference (90% CI) 91, 46
Reference (90%CI) Test Reference (90%CI) 88.84
2. 264, 3
2,264.3
2. 308, 6
2,308.6
(92, 28;
(92.28,
2. 130, 6
2,130.6
2. 384, 4
2,384.4
(84, 02;
(84.02,
(ng/ ml)
(84.64,
AUC0- t 125. 623, 6 132. 795, 7
AUC0-last
(90, 73;
125,623.6 132,795.7
10. 682, 6
(90.73,
10. 874, 4
10,682.6 10,874.4
(94, 90;
(94.90,
1. 948, 8
1,948.8
1. 969, 0
1,969.0
(91, 02;
(91.02,
(ng· t/ ml) (25, 7)
(ng·h/ ml)
(27, 0)
(25.7) (27.0)
(14, 9)
(18.1) (14.9)
AUCin 146. 074, 9 155. 518, 6
AUCinf
(89, 63;
146,074.9 155,518.6
10. 854, 9
(89.63,
11. 054, 3
10,854.9 11,054.3
(94, 86;
(94.86,
2. 314, 0
2,314.0
2. 319, 4
2,319.4
(93, 22;
(93.22,
(ng· t/ ml) (33, 1)
(ng·h/ ml)
(34, 6)
(33.1) (34.6)
(14, 9)
(17.9) (14.9)
(t)
T1/ 2 (h)
(53, 8)
180.6 182.5 (45.3) (38.3)
(47, 8)
14.5 14.6 (53.8) (47.8)
(20, 8)
18.9 (20.8)
(22, 6)
17.8 (22.6)
Reference:
Test: single fixed-dose combination tablet taken under fasted conditions.
Enkelt dosis 600 mg efavirenztablet, 200 mg emtricitabinkapsel og 300 mg tenofovirdisoproxilfumarattablet taget under faste.
Reference: single dose of a 600 mg efavirenz tablet, 200 mg emtricitabine capsule and 300 mg tenofovir disoproxil fumarate tablet taken under fasted conditions.
Værdierne for Test og Reference er gennemsnitlige (% variationskoefficient) GMR:
Values for Test and Reference are mean (% coefficient of variation).
Geometriske mindste kvadraters mean ratio, CI=konfidensinterval
GMR=geometric least-squares mean ratio, CI=confidence interval
De højeste efavirenz- plasmakoncentrationer hos HIV- inficerede patienter blev opnået efter 5 timer og steady- state- koncentrationerne blev nået på 6- 7 dage.
Absorption: in HIV infected patients, peak efavirenz plasma concentrations were attained by 5 hours and steady-state concentrations reached in 6 to 7 days.
Hos 35 patienter, der fik 600 mg efavirenz en gang dagligt, var den højeste steady- state- koncentration (Cmax) 12, 9 ± 3, 7 µM (29%) [middel ± standarddeviation (S. D.) (variationskoefficient (% CV))], steady- state Cmin var 5, 6 ± 3, 2 µM (57%) og AUC var 184 ± 73 µM· t (40%).
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%).
Emtricitabin absorberes hurtigt, og de højeste plasmakoncentrationer forekom 1- 2 timer efter dosering.
Emtricitabine is rapidly absorbed with peak plasma concentrations occurring at 1 to 2 hours post-dose.
Efter oral administration af multiple emtricitabindoser til 20 HIV- inficerede patienter var steady- state Cmax 1, 8 ± 0, 7 µg/ ml (middel ± S. D.) (39% CV), steady- state Cmin var 0, 09 ± 0, 07 µg/ ml (80%) og AUC var 10, 0 ± 3, 1 µg· t/ ml (31%) i løbet af et 24- timers doseringsinterval.
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.
Efter oral administration af en enkelt dosis tenofovirdisoproxilfumarat 300 mg til HIV- 1- inficerede patienter i faste opnåedes maksimal tenofovirkoncentration inden for en time og Cmax og AUC (middel ± S. D.) (% CV) værdierne var henholdsvis 296 ± 90 ng/ ml (30%) og 2. 287 ± 685 ng· t/ ml (30%).
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.
25%.
The oral bioavailability of tenofovir from tenofovir disoproxil fumarate in fasted patients was approximately 25%.
Virkning af mad:
Effect of food:
31 Administration af efavirenzkapsler sammen med et måltid med stort fedtindhold forhøjede gennemsnitligt AUC og Cmax af efavirenz med henholdsvis 28% og 79% sammenlignet med administration under faste.
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.
Sammenlignet med administration under faste blev tenofovirs gennemsnitlige AUC og Cmax forhøjet med henholdsvis 35% og 15% ved dosering af tenofovirdisoproxilfumarat og emtricitabin i kombination med enten et fedtrigt eller et let måltid uden at påvirke emtricitabin- eksponeringen.
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.
4. 4 og 4. 8).
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).
35% lavere efter administration af Atripla på tom mave sammenlignet med den individuelle komponent tenofovirdisoproxilfumarat, når denne tages sammen med mad.
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.
48- ugers- data fra en klinisk undersøgelse (AI266073) viste opretholdelse af virologisk suppression hos patienter, som havde stabil virologisk suppression på antiretroviral kombinationsbehandling, og som efterfølgende skiftede til Atripla med anbefaling om administration af Atripla på tom mave.
Forty-eight week data from a clinical study (AI266073) showed maintenance of virologic suppression for patients who had stable virologic suppression on combination
Efavirenz har en høj bindingsgrad (> 99%) til humane plasmaproteiner, fortrinsvis albumin.
Distribution: efavirenz is highly bound (> 99%) to human plasma proteins, predominantly albumin.
In vitro- binding af emtricitabin til humane plasmaproteiner er < 4% og uafhængig af koncentrationer i området 0, 02 til 200 µg/ ml.
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.
1, 4 l/ kg.
Following intravenous administration the volume of distribution of emtricitabine was approximately 1.4 l/ kg.
4, 0.
The mean plasma to blood concentration ratio was approximately 1.0 and the mean semen to plasma concentration ratio was approximately 4.0.
In vitro- binding af tenofovir til humane plasma - eller serumproteiner ligger henholdsvis < 0, 7% og 7, 2% over tenofovirs koncentrationsområde på 0, 01 til 25 µg/ ml.
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.
800 ml/ kg.
Following intravenous administration the volume of distribution of tenofovir was approximately 800 ml/ kg.
Humane undersøgelser og in vitro- undersøgelser med anvendelse af humane levermikrosomer har vist, at efavirenz hovedsageligt metaboliseres til hydroxylerede metabolitter af cytokrom P450- systemet med efterfølgende glucuronidering af disse hydroxylerede metabolitter.
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.
Disse metabolitter er stort set inaktive over for HIV- 1.
These metabolites are essentially inactive against HIV-1.
In vitro- undersøgelserne tyder på, at CYP3A4 og CYP2B6 er de isoenzymer, der hovedsageligt er ansvarlige for efavirenz- metaboliseringen, og at det hæmmer P450 isoenzymerne 2C9, 2C19 og 3A4.
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.
I in vitro- undersøgelser hæmmede efavirenz ikke CYP2E1og hæmmede kun CYP2D6 og CYP1A2 ved koncentrationer, der lå langt over de klinisk opnåede.
In in vitro studies efavirenz did not inhibit CYP2E1 and inhibited CYP2D6 and CYP1A2 only at concentrations well above those achieved clinically.
Efavirenz plasmaeksponering kan øges hos patienter med homozygot- G516T, der er en genetisk variant af CYP2B6- isoenzymet.
Efavirenz plasma exposure may be increased in patients with homozygous G516T genetic variant of the CYP2B6 isoenzyme.
Det er påvist, at efavirenz inducerer P450- enzymer, hvilket medfører induktion af dets egen metabolisme.
Efavirenz has been shown to induce P450 enzymes, resulting in the induction of its own metabolism.
Hos ikke- inficerede frivillige resulterede multiple doser på 200- 400 mg per dag i 10 dage i en lavere grad af akkumulation (22- 42% lavere) end forudset samt kortere terminal halveringstid på 40- 55 timer (halveringstid for enkeltdosis 52- 76 timer).
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).
4% af dosis).
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).
In vitro- undersøgelser har afgjort, at hverken tenofovirdisoproxilfumarat eller tenofovir er substrater for CYP450- enzymerne.
In vitro studies have determined that neither tenofovir disoproxil fumarate nor tenofovir are substrates for the CYP450 enzymes.