natgillin/translations-raw huggingface dataset:
Kombineret 48 ugers behandlingsrespons (sammensat endpoint defineret som patienter med et bekræftet log RNA fald ≥1 i forhold til baseline og uden påvisning af behandlingsfejl) for begge forsøg var 34% i APTIVUS/ ritonavir- gruppen og 15% i komparatorgruppen.
Combined 48-week treatment response (composite endpoint defined as patients with a confirmed ≥ 1 log RNA drop from baseline and without evidence of treatment failure) for both studies was 34% in the APTIVUS/ ritonavir arm and 15% in the comparator arm.
Behandlingsrespons * i uge 48 (poolede RESIST- 1 - og RESIST- 2- forsøg med behandlede patienter)
Treatment response* at week 48 (pooled studies RESIST-1 and RESIST-2 in treatment- experienced patients)
RESIST- forsøg
RESIST study
Alle forsøgspersoner
Overall population
FAS PP - med ENF (FAS) - uden ENF (FAS) Genotypisk resistens LPV/ rtv
FAS PP - with ENF (FAS) - without ENF (FAS) Genotypically Resistant LPV/ rtv
< < < <
< 0.0001 < 0.0001 < 0.0001 < 0.0001
< <
< 0.0001 < 0.0001
0, 0001 0, 0010
< 0.0001 0.0010
0, 0001 0, 0650
< 0.0001 0.0650
* Det endelige respons defineret som patienter med bekræftet 1 log RNA- fald i forhold til baseline og uden tegn på behandlingssvigt ** Komparator proteasehæmmer/ RTV:
* Composite endpoint defined as patients with a confirmed 1 log RNA drop from baseline and without evidence of treatment failure ** Comparator PI/ RTV:
Saquinavir/ ritonavir
LPV/ r 400/ 100 mg bid (n=358), IDV/ r 800/ 100 mg bid (n=23), SQV/ r 1000/ 100 mg bid or 800/ 200 mg bid (n=162), APV/ r 600/ 100 mg bid (n=194) ENF Enfuvirtide; FAS Full Analysis Set; PP Per Protocol; APV/ rtv Amprenavir/ ritonavir; IDV/ rtv Indinavir/ ritonavir; LPV/ rtv Lopinavir/ ritonavir; SQV/ rtv Saquinavir/ ritonavir
Kombineret 48 ugers mediantid til behandlingssvigt for begge undersøgelser var 115 dage i APTIVUS/ ritonavir- gruppen og 0 dage i komparatorgruppen (intet behandlingsrespons var tillagt til dag 0).
Combined 48-week median time to treatment failure for both studies was 115 days in the APTIVUS/ ritonavir arm and 0 days in the comparator arm (no treatment response was imputed to day 0).
18 Gennem 48 ugers behandling var andelen af patienter i APTIVUS/ ritonavir- gruppen i forhold til komparator- proteasehæmmer/ ritonavir- gruppen med HIV- 1 RNA < 400 viruspartikler/ ml henholdsvis 30% og 14%, og med HIV- 1 RNA < 50 viruspartikler/ ml henholdsvis 23% og 10%.
Through 48 weeks of treatment, the proportion of patients in the APTIVUS/ ritonavir arm compared to the comparator PI/ ritonavir arm with HIV-1 RNA < 400 copies/ ml was 30% and 14% respectively, and with HIV-1 RNA < 50 copies/ ml was 23% and 10% respectively.
Blandt alle randomiserede og behandlede patienter var median ændringen fra baseline i HIV- 1 RNA ved sidste måling op til uge 48 - 0, 64 log10 viruspartikler/ ml hos patienter, der har fået APTIVUS/ ritonavir i modsætning til - 0, 22 log10 viruspartikler/ ml i komparator- proteasehæmmer/ ritonavir- gruppen.
Among all randomised and treated patients, the median change from baseline in HIV-1 RNA at the last measurement up to Week 48 was -0.64 log10 copies/ ml in patients receiving APTIVUS/ ritonavir versus -0.22 log10 copies/ ml in the comparator PI/ ritonavir arm.
Blandt alle randomiserede og behandlede patienter, var median ændringen i CD4+- celletællingen ved baseline ved sidste måling op til uge 48 +23 celler/ mm3 hos patienter, der får APTIVUS/ ritonavir (N=740) i modsætning til +4 celler/ mm3 i komparator- proteasehæmmer/ ritonavir- gruppen (N=727).
19 Among all randomised and treated patients, the median change from baseline in CD4+ cell count at the last measurement up to Week 48 was +23 cells/ mm3 in patients receiving APTIVUS/ ritonavir (N=740) versus +4 cells/ mm3 in the comparator PI/ ritonavir (N=727) arm.
Overlegenheden ved APTIVUS indgivet sammen med lavdosis ritonavir i forhold til komparator - proteasehæmmer/ ritonavir- gruppen sås efter 48 uger for alle effektparametre.
The superiority of APTIVUS co-administered with low dose ritonavir over the comparator protease inhibitor/ ritonavir arm was observed for all efficacy parameters at week 48.
Det er ikke vist, at APTIVUS er overlegen til disse boostede komporator protease- inhibitor hos patienter, der har stammer, som er modtagelige over for disse proteasehæmmere.
It has not been shown that APTIVUS is superior to these boosted comparator protease inhibitors in patients harbouring strains susceptible to these protease inhibitors.
RESIST- data viser også, at APTIVUS indgivet sammen med lavdosis ritonavir viser et bedre behandlingsrespons efter 48 uger, når den optimerede baggrundsbehandling indeholder genotypisk tilgængelige antiretrovirale midler (fx enfuvirtid).
RESIST data also demonstrate that APTIVUS co- administered with low dose ritonavir exhibits a better treatment response at 48 weeks when the OBR contains genotypically available antiretroviral agents (eg enfuvirtide).
På nuværende tidspunkt er der ingen resultater fra kontrollerede forsøg, der vurderer effekten af APTIVUS på den kliniske udvikling af HIV.
At present there are no results from controlled trials evaluating the effect of APTIVUS on clinical progression of HIV.
Analyse af tipranavir- resistens hos tidligere behandlede patienter:
Analyses of tipranavir resistance in treatment experienced patients:
Responsrater for APTIVUS/ ritonavir i RESIST- studierne blev vurderet ud fra baseline tipranavir genotype og fænotype.
APTIVUS/ ritonavir response rates in the RESIST studies were assessed by baseline tipranavir genotype and phenotype.
Forholdene mellem baseline fænotypisk modtagelighed over for tipranavir, primære proteasehæmmermutationer, proteasemutationer ved codon 33, 82, 84 og 90, mutationer i forbindelse med tipranavirresistens og respons på behandling med APTIVUS/ ritonavir blev vurderet.
Relationships between baseline phenotypic susceptibility to tipranavir, primary PI mutations, protease mutations at codons 33, 82, 84 and 90, tipranavir resistance-associated mutations, and response to APTIVUS/ ritonavir therapy were assessed.
Det skal bemærkes, at patienterne i RESIST- studierne udviste et specifikt mutationsmønster ved baseline på mindst én primær proteasegenmutation blandt codon 30N, 46I, 46L, 48V, 50V, 82A, 82F, 82L, 82T, 84V eller 90M og højst 2 mutationer ved codon 33, 82, 84 eller 90.
Of note, patients in the RESIST studies had a specific mutational pattern at baseline of at least one primary protease gene mutation among codons 30N, 46I, 46L, 48V, 50V, 82A, 82F, 82L, 82T, 84V or 90M, and no more than two mutations on codons 33, 82, 84 or 90.
- Primære proteasehæmmermutationer:
− Primary PI mutations:
Der blev foretaget analyser med henblik på at vurdere det virologiske resultat på basis af antallet af primære proteasehæmmermutationer, der forelå ved baseline (enhver ændring ved proteasecodon 30, 32, 36, 46, 47, 48, 50, 53, 54, 82, 84, 88 og 90).
Analyses were conducted to assess virological outcome by the number of primary PI mutations (any change at protease codons 30, 32, 36, 46, 47, 48, 50, 53, 54, 82, 84, 88 and 90) present at baseline.
Dette gjaldt både for patienter, der havde påbegyndt enfuvirtid ved studiestart og de, der ikke havde påbegyndt enfuvirtid.
Response rates were higher in APTIVUS/ ritonavir patients than comparator PI boosted with ritonavir in new enfuvirtide patients, or patients without new enfuvirtide.
- Mutationer ved proteasecodon 33, 82, 84 og 90:
− Mutations at protease codons 33, 82, 84 and 90:
Der blev observeret nedsat virologisk respons hos patienter med virusstrenge, som havde to eller flere mutationer ved HIV- proteasecodon 33, 82, 84 eller 90, og som ikke havde modtaget ny enfuvirtid.
A reduced virological response was observed in patients with viral strains harbouring two or more mutations at HIV protease codons 33, 82, 84 or 90, and not receiving new enfuvirtide.
- Mutationer i forbindelse med tipranavir- resistens:
− Tipranavir resistance-associated mutations:
Virologisk respons over for APTIVUS/ ritonavir- behandling er vurderet ud fra en tipranavir- relateret mutationsscore baseret på baseline genotype hos patienter, der deltog i RESIST- 1 og RESIST- 2.
Virological response to APTIVUS/ ritonavir therapy has been evaluated using a tipranavir-associated mutation score based on baseline genotype in RESIST-1 and RESIST-2 patients.
Denne score (opgjort ved at tælle de 16 aminosyrer, der er forbundet med nedsat følsomhed over for tipranavir og/ eller nedsat virusmængde- respons:
This score (counting the 16 amino acids that have been associated with reduced tipranavir susceptibility and/ or reduced viral load response:
10V, 13V, 20M/ R/ V, 33F, 35G, 36I, 43T, 46L, 47V, 54A/ M/ V, 58E, 69K, 74P, 82L/ T, 83D og 84V) blev anvendt ved baseline virusproteasesekvenser.
10V, 13V, 20M/ R/ V, 33F, 35G, 36I, 43T, 46L, 47V, 54A/ M/ V, 58E, 69K, 74P, 82L/ T, 83D and 84V) was applied to baseline viral protease sequences.
Man så en sammenhæng mellem mutationsscoren for tipranavir og responsen over for APTIVUS/ ritonavir- behandling ved uge 48.
A correlation between the tipranavir mutation score and response to APTIVUS/ ritonavir therapy at week 48 has been established.
Der rådes derfor til forsigtighed med hensyn til at ekstrapolere til en bredere population.
This score has been determined from the selected RESIST patient population having specific mutation inclusion criteria and therefore extrapolation to a wider population mandates caution.
Efter 48 uger nåede en større andel af de patienter, der fik APTIVUS/ ritonavir- behandling et behandlingsrespons sammenlignelig med komparator proteasehæmmer/ ritonavir for næsten alle mulige kombinationer af genotypisk resistensmutation (se tabel nedenfor).
At 48-weeks, a higher proportion of patients receiving APTIVUS/ ritonavir achieved a treatment response in comparison to the comparator protease inhibitor/ ritonavir for nearly all of the possible combinations of genotypic resistance mutations (see table below).
Delen af patienter, der opnår behandlingsrespons ved uge 48 (bekræftet ≥1 log10 kopier/ ml fald i virusmængde sammenlignet med baseline) i henhold til tipranavir baseline- mutationsscore og anvendelse af enfuvirtid til RESIST- patienter.
20 Proportion of patients achieving treatment response at Week 48 (confirmed ≥ 1 log10 copies/ ml decrease in viral load compared to baseline), according to tipranavir baseline mutation score and enfuvirtide use in RESIST patients
Ingen ny ENF *
No New ENF*
Antal af TPV Score mutationer **
Number of TPV Score Mutations**
0, 1 2 3 4 ≥5 Alle patienter
0,1 2 3 4 ≥ 5 All patients
73% 61% 75% 59% 47% 61%
73% 61% 75% 59% 47% 61%
53% 33% 27% 23% 13% 29%
53% 33% 27% 23% 13% 29%
Tipranavir/ ritonavir
* Includes patients who did not receive ENF and those who were previously treated with and continued ENF **Mutations in HIV protease at positions L10V, I13V, K20M/ R/ V, L33F, E35G, M36I, K43T, M46L, I47V, I54A/ M/ V, 58E, H69K, T74P, V82L/ T, N83D or I84V ENF Enfuvirtide; TPV/ r Tipranavir/ ritonavir
Vedvarende fald i HIV- 1 RNA frem til uge 48 blev hovedsageligt observeret hos patienter, som modtog APTIVUS/ ritonavir og ny enfuvirtid.
Sustained HIV-1 RNA decreases up to week 48 were mainly observed in patients who received APTIVUS/ ritonavir and new enfuvirtide.
Hos patienter, som ikke modtog APTIVUS/ ritonavir med ny enfuvirtid, blev der observeret nedsat behandlingsrespons ved uge 48 set i forhold til brug af ny enfuvirtid (se tabel nedenfor).
If patients did not receive APTIVUS/ ritonavir with new enfuvirtide, diminished treatment responses at week 48 were observed, relative to new enfuvirtide use (see Table below).
Gennemsnitligt fald i virusmængde fra baseline til uge 48 i henhold til tipranavir baseline - mutationsscore og anvendelse af enfuvirtid til RESIST- patienter
Mean decrease in viral load from baseline to week 48, according to tipranavir baseline mutation score and enfuvirtide use in RESIST patients
0, 1 2 3 4 ≥5 Alle patienter
0, 1 2 3 4 ≥ 5 All patients
Tipranavir/ ritonavir
* Includes patients who did not receive ENF and those who were previously treated with and continued ENF ** **Mutations in HIV protease at positions L10V, I13V, K20M/ R/ V, L33F, E35G, M36I, K43T, M46L, I47V, I54A/ M/ V, 58E, H69K, T74P, V82L/ T, N83D or I84V ENF Enfuvirtide; TPV/ r Tipranavir/ ritonavir
20 − Tipranavir fænotypisk resistens:
− Tipranavir phenotypic resistance:
Hvis der i isolater ses en stigning i baseline fænotypiske ændringer p. g. a. tipranavis, er det tegn på nedsat virologisk respons.
Increasing baseline phenotypic fold change to tipranavir in isolates is correlated to decreasing virological response.
Isolater med ændringer på > 3- 10 fold har nedsat følsomhed, mens isolater med ændringer på > 10 fold er resistente.
Isolates with baseline fold change of > 0 to 3 are considered susceptible; isolates with > 3 to 10 fold changes have decreased susceptibility; isolates with > 10 fold changes are resistant.
5. 2 Farmakokinetiske egenskaber
21 5.2 Pharmacokinetic properties
4. 2).
In order to achieve effective tipranavir plasma concentrations and a twice daily dosing regimen, coadministration of tipranavir with low dose ritonavir twice daily is essential (see section 4.2).
Ritonavir hæmmer det hepatiske cytokrom P450 CYP3A, udstrømningspumpen for P- glykoprotein (Pgp) i tarmen og muligvis også cytokrom P450 CYP3A i tarmen.
Ritonavir acts by inhibiting hepatic cytochrome P450 CYP3A, the intestinal P-glycoprotein (Pgp) efflux pump and possibly intestinal cytochrome P450 CYP3A as well.
Som påvist i et dosisvariende forsøg med 113 HIV - negative, raske mandlige og kvindelige frivillige øger ritonavir AUC0- 12t, Cmax og Cmin og nedsætter clearance af tipranavir.
As demonstrated in a dose- ranging evaluation in 113 HIV-negative healthy male and female volunteers, ritonavir increases AUC0- 12h, Cmax and Cmin and decreases the clearance of tipranavir.
Tipranavir givet sammen med lavdosis ritonavir (500 mg/ 200 mg to gange daglig) resulterede i en 29 gange øgning i den geometiske mean morgen steadystate ” trough ” plasmakoncentration sammenlignet med tipranavir 500 mg to gange daglig uden ritonavir
Tipranavir co-administered with low dose ritonavir (500 mg/ 200 mg twice daily) was associated with a 29-fold increase in the geometric mean morning steady-state trough plasma concentrations compared to tipranavir 500 mg twice daily without ritonavir.
Tipranavir er et Pgp- substrat, en svag Pgp- hæmmer og synes også at være en kraftig Pgp- inducer.
Tipranavir is a Pgp substrate, a weak Pgp inhibitor and appears to be a potent Pgp inducer as well.
Data tyder på, at selvom ritonavir er en Pgp- hæmmer, er nettopåvirkningen af APTIVUS givet sammen med lavdosis ritonavir ved det foreslåede dosisregime ved steadystate Pgp- induktion.
Data suggest that, although ritonavir is a Pgp inhibitor, the net effect of APTIVUS, co-administered with low dose ritonavir, at the proposed dose regimen at steady-state, is Pgp induction.
Peak- plasmakoncentrationer nås i løbet af 1- 5 timer efter indgift afhængig af den anvendte dosis.
Peak plasma concentrations are reached within 1 to 5 hours after dose administration depending upon the dosage used.
Ved gentagne doser er plasmakoncentrationerne af tipranavir lavere end forventet fra enkeltdosis- data, sandsynligvis pga. hepatisk enzym- induktion.
With repeated dosing, tipranavir plasma concentrations are lower than predicted from single dose data, presumably due to hepatic enzyme induction.
Steadystate opnås hos de fleste personer efter 7 dages indgift.
Steady-state is attained in most subjects after 7 days of dosing.
Tipranavir, indgivet samtidig med lavdosis ritonavir, viser lineær farmakokinetik ved steadystate.
Tipranavir, co-administered with low dose ritonavir, exhibits linear pharmacokinetics at steady state.
3 timer efter indgift.
Dosing with APTIVUS 500 mg concomitant with 200 mg ritonavir twice daily for 2 to 4 weeks and without meal restriction produced a mean tipranavir peak plasma concentration (Cmax) of 94.8 ± 22.8 µM for female patients (n=14) and 77.6 ± 16.6 µM for male patients (n=106), occurring approximately 3 hours after administration.
Middel steadystate’ trough ’ - koncentration før morgendosis var 41, 6 + / - 24, 3 µM for kvindelige patienter og 35, 6 + / - 16, 7 µM for mandlige patienter.
The mean steady-state trough concentration prior to the morning dose was 41.6 ± 24.3 µM for female patients and 35.6 ± 16.7 µM for male patients.
AUC for tipranavir var i løbet af et 12- timers doseringsinterval gennemsnitligt 851 + / - 309 µM. t (CL=1, 15 l/ t) for kvindelige patienter og 710 + / - 207 µM. t (CL=1, 27 l/ t) for mandlige patienter.
Tipranavir AUC over a 12 hour dosing interval averaged 851 ± 309 µM• h (CL=1.15 l/ h) for female patients and 710 ± 207 µM • h (CL=1.27 l/ h) for male patients.
Halveringstiden er gennemsnitligt mellem 5, 5 (for kvinder) og 6, 0 (for mænd).
The mean half-life was 5.5 (females) or 6.0 hours (males).
Virkningen af føde på peroral absorption:
Effects of food on oral absorption:
Mad forbedrer, hvor godt tipranavir/ ritonavir tåles.
Food improves the tolerability of tipranavir/ ritonavir.
APTIVUS givet sammen med lavdosis ritonavir bør derfor gives med mad.
Therefore APTIVUS, co-administered with low dose ritonavir, should be given with food.
Der afventes data, som kan fastslå madens indvirkning på peroral adsorption.
Data are awaited to substantiate the influence of food on oral absorption.
4. 5).
Absorption of tipranavir, co-administered with low dose ritonavir, is reduced in the presence of antacids (see section 4.5).
Tipranavir er i høj grad bundet til plasmaproteiner (> 99, 9%).
Tipranavir is extensively bound to plasma proteins (> 99.9%).
Fra raske frivillige og HIV - 1- positive forsøgspersoner, som fik tipranavir uden ritonavir, var mean- tallet for ubundet tipranavir i plasma det samme i begge populationer (raske frivillige 0, 015% ± 0, 006%; HIV- positive forsøgspersoner 0, 019% + / - +0, 076%).
From clinical samples of healthy volunteers and HIV-1 positive subjects who received tipranavir without ritonavir the mean fraction of tipranavir unbound in plasma was similar in both populations (healthy volunteers 0.015% ± 0.006%; HIV-positive subjects 0.019% ± 0.076%).
Totale plasmakoncentrationer af tipranavir varierede fra 9 til 82 µM.
Total plasma tipranavir concentrations for these samples ranged from 9 to 82 µM.
Den ubundne del af tipranavir var uafhængig af den samlede lægemiddelkoncentration i dette koncentrationsinterval.
The unbound fraction of tipranavir appeared to be independent of total drug concentration over this concentration range.
Der er ikke gennemført forsøg for at fastlægge fordelingen af tipranavir i rygmarvsvæske eller sæd hos mennesker.
No studies have been conducted to determine the distribution of tipranavir into human cerebrospinal fluid or semen.
21 Metabolisme:
Metabolism:
In vitro metabolismeforsøg med humane levermikrosomer indikerede, at CYP3A4 er den dominerende CYP- isoform, der indgår i tipranavir- metabolismen.
In vitro metabolism studies with human liver microsomes indicated that CYP3A4 is the predominant CYP isoform involved in tipranavir metabolism.
Den orale clearance af tipranavir faldt efter tilførsel af ritonavir, hvilket kan skyldes nedsat first- pass - clearance af lægemidlet i mave/ tarm- kanalen og leveren.
The oral clearance of tipranavir decreased after the addition of ritonavir which may represent diminished first-pass clearance of the drug at the gastrointestinal tract as well as the liver.
I et humant 14C - tipranavir- forsøg (14C- tipranavir/ ritonavir, 500 mg/ 200 mg to gange daglig) udgjorde uforbundet tipranavir 98, 4% eller mere af den totale cirkulerende plasmaradioaktivitet, 3, 8 eller 12 timer efter dosering.
In a 14C-tipranavir human study (14C-tipranavir/ ritonavir, 500 mg/ 200 mg twice daily), unchanged tipranavir was predominant and accounted for 98.4% or greater of the total plasma radioactivity circulating at 3, 8, or
Der blev kun fundet nogle få metabolitter i plasma, og alle var på sporniveau (0, 2% eller mindre af plasmaens radioaktivitet).
Only a few metabolites were found in plasma, and all were at trace levels (0.2% or less of the plasma radioactivity).
I fæces var uforandret tipranavir hovedparten af radioaktiviteten (79, 9% af radioaktiviteten i fæces).
In faeces, unchanged tipranavir represented the majority of faecal radioactivity (79.9% of faecal radioactivity).
4, 9% af radioaktiviteten (3, 2% af dosis) var en hydroxylmetabolit fra tipranavir.
The most abundant faecal metabolite, at 4.9% of faecal radioactivity (3.2% of dose), was a hydroxyl metabolite of tipranavir.
I urinen blev der fundet uændret tipranavir i spormængder (0, 5% af urinens radioaktivitet).
In urine, unchanged tipranavir was found in trace amounts (0.5% of urine radioactivity).
11, 0% af radioaktiviteten (0, 5% af dosis) var et glucuronid- konjugat fra tipranavir.
The most abundant urinary metabolite, at 11.0% of urine radioactivity (0.5% of dose) was a glucuronide conjugate of tipranavir.
Indgift af 14C- tipranavir til forsøgspersoner (n=8), som fik tipranavir/ ritonavir 500 mg/ 200 mg to gange daglig viste ved steadystate, at størstedelen af radioaktiviteten (middel 82, 3%) blev udskilt i fæces, hvorimod kun gennemsnitlig 4, 4% blev genfundet i urinen.
Administration of 14C-tipranavir to subjects (n = 8) that received tipranavir/ ritonavir 500 mg/ 200 mg twice daily dosed to steady-state demonstrated that most radioactivity (median 82.3%) was excreted in faeces, while only a median of 4.4% of the radioactive dose administered was recovered in urine.
4, 8 og 6, 0 timer ved steadystate efter en dosis på 500 mg/ 200 mg to gange daglig indtages med et let måltid.
The effective mean elimination half-life of tipranavir/ ritonavir in healthy volunteers (n = 67) and HIV- infected adult patients (n = 120) was approximately 4.8 and 6.0 hours, respectively, at steady state following a dose of 500 mg/ 200 mg twice daily with a light meal.
Selvom de foreliggende data på nuværende tidspunkt er for begrænsede til at tillade en definitiv analyse, tyder de på, at den farmakokinetiske profil er uændret hos ældre og sammenlignelig mellem racer.
Although data available at this stage are currently limited to allow a definitive analysis, they suggest that the pharmacokinetic profile is unchanged in elderly and comparable between races.
I modsætning hertil viser evaluering af steady- state "trough" plasmakoncentrationer af tipranavir 10- 14 timer efter dosering i forsøgene RESIST- 1 og RESIST- 2, at kvinder generelt havde højere koncentrationer af tipranavir end mænd.
By contrast, evaluation of the steady-state plasma tipranavir trough concentrations at 10-14 h after dosing from the RESIST-1 and RESIST-2 studies demonstrate that females generally had higher tipranavir concentrations than males.
Efter 4 uger med APTIVUS/ ritonavir (500 mg/ 200 mg to gange daglig var middel "trough" plasmakoncentrationen af tipranavir 43, 9 µM for kvinder og 31, 1 µM for mænd.
After four weeks of APTIVUS/ ritonavir (500 mg/ 200 mg twice daily) the median plasma trough concentration of tipranavir was 43.9 µM for females and 31.1 µM for males.
Nyreinsufficiens:
Renal dysfunction:
Leverinsufficiens:
Hepatic dysfunction:
I et forsøg, der sammenlignede 9 patienter med mild (Child- Pugh A) lever insufficiens med 9 kontrolpersoner, øgedes farmakokinetikken for enkeltdoser og multiple doser af tipranavir og ritonavir hos patienter med lever insufficiens, men stadig inden for intervallet som observeret i de kliniske forsøg.
In a study comparing 9 patients with mild (Child-Pugh A) hepatic impairment to 9 controls, the single and multiple dose exposure of tipranavir and ritonavir were increased in patients with hepatic impairment but still within the range observed in clinical studies.
4. 2 og 4. 4).
No dosing adjustment is required in patients with mild hepatic impairment but patients should be closely monitored (see sections 4.2 and 4.4).
Indflydelsen af moderat (Child- Pugh B) eller alvorlig (Child- Pugh C) lever insufficiens på fler - dosisfarmakokinetikken for enten tipranavir eller ritonavir er endnu ikke klarlagt APTIVUS er kontraindiceret ved moderat eller svær leverinsufficiens (se pkt.
APTIVUS is contraindicated in moderate or severe hepatic impairment (see sections 4.2 and 4.3).