natgillin/translations-raw huggingface dataset:
Da disse data kommer fra det spontane rapporteringssystem er frekvenserne ikke kendt.
As these data come from the spontaneous reporting system, the frequency of the adverse reactions is unknown.
16
16 • Immune system disorders:
4. 4).
- Diabetes mellitus or hyperglycaemia sometimes associated with ketoacidosis (see section 4.4).
- Lipodystrofi:
- Lipodystrophy:
Antiretroviral kombinationsbehandling er hos patienter med hiv associeret med
Combination antiretroviral therapy has been associated with redistribution of
omfordeling af kropsfedt (lipodystrofi), inklusiv tab af perifert subkutant fedt og subkutant fedt i ansigtet, øget intraabdominalt og visceralt fedt, brysthypertrofi og dorsocervikal fedtakkumulering (bøffel- pukkel).
body fat (lipodystrophy) in HIV infected patients including the loss of peripheral and facial subcutaneous fat, increased intra-abdominal and visceral fat, breast hypertrophy and dorsicervical fat accumulation (buffalo hump).
- Antiretroviral kombinationsbehandling er blevet associeret med metaboliske abnormaliteter
- Combination antiretroviral therapy has been associated with metabolic abnormalities such as
4. 4).
hypertriglyceridaemia, hypercholesterolaemia, insulin resistance, hyperglycaemia and hyperlactataemia (see section 4.4).
• Nervesystemet:
• Nervous system disorders:
Somnolens, kramper.
Somnolence, convulsions.
• Vaskulære sygdomme:
• Vascular disorders:
4. 4).
There have been reports of increased bleeding, including spontaneous skin haematomas and haemarthroses, in haemophilic patients type A and B treated with protease inhibitors (see section 4.4).
• Lever og galdeveje:
• Hepato-biliary disorders:
Hepatitis.
Hepatitis.
• Knogler, led, muskler og bindevæv:
• Musculoskeletal, connective tissue and bone disorders:
Forøget CPK, myalgi, myositis og i sjældne tilfælde rhabdomyolyse ved brug af proteasehæmmere, specielt i kombination med nukleosidanaloger.
Increased CPK, myalgia, myositis and rarely, rhabdomyolysis have been reported with protease inhibitors, particularly in combination with nucleoside analogues.
Særligt hos patienter med generelt anerkendte risikofaktorer, fremskreden hiv- sygdom eller langvarig kombinationsbehandling med antiretrovirale lægemidler (CART) er der rapporteret om tilfælde af osteonekrose.
Cases of osteonecrosis have been reported, particularly in patients with generally acknowledged risk factors, advanced HIV disease or long-term exposure to combination antiretroviral therapy (CART).
• Nyrer og urinveje:
• Renal and urinary disorders:
4. 4).
• In HIV-infected patients with severe immune deficiency at the time of initiation of combination antiretroviral therapy (CART), an inflammatory reaction to asymptomatic or residual opportunistic infections may arise (see section 4.4).
Behandlingen for overdosering med saquinavir bør bestå af generel støttende behandling, herunder overvågning af vitale tegn og EKG, samt observationer af patientens kliniske situation.
Treatment of overdose with saquinavir should consist of general supportive measures, including monitoring of vital signs and ECG, and observations of the patient ’ s clinical status.
J05AE01.
Antiviral agent, ATC code J05A E01
Hiv- protease er et essentielt viralt enzym, der er nødvendigt for den specifikke spaltning af virale gag og gag- pol polyproteiner.
The HIV protease is an essential viral enzyme required for the specific cleavage of viral gag and gag-pol polyproteins.
Saquinavir hæmmer selektivt hiv- proteasen, hvorved dannelsen af modne, infektiøse viruspartikler forhindres
Saquinavir selectively inhibits the HIV protease, thereby preventing the creation of mature infectious virus particles.
Antiviral aktivitet in vitro:
17 Antiviral activity in vitro:
De
Saquinavir demonstrates antiviral activity against a panel of laboratory strains and clinical isolates of HIV-1 with typical EC50 and EC90 values in the range 1-10 nM and 5-50 nM, respectively, with no apparent difference between subtype B and non-B clades.
17 korresponderende serum- justerede (50% human serum) EC50- værdier var i intervallet 25- 250 nM.
The corresponding serum (50% human serum) adjusted EC50 ranged from 25-250 nM.
Kliniske isolater af hiv- 2 gav EC50- værdier i intervallet fra 0, 3- 2, 4 nM.
Clinical isolates of HIV-2 demonstrated EC50 values in the range of 0.3-2.4 nM.
Antiviral aktivitet i henhold til baseline- genotype og fænotype:
Antiviral activity according to baseline genotype and phenotype:
Genotypiske og fænotypiske, kliniske skæringspunkter, som forudsiger den kliniske effekt af ritanovir boostet saquinavir, er blevet fastlagt på baggrund af retrospektive analyser af RESIST 1 - og 2 - studierne samt analyse af en stor hospital kohorte (Marcelin et al 2007).
Genotypic and phenotypic clinical cut-offs predicting the clinical efficacy of ritonavir boosted saquinavir have been derived from retrospective analyses of the RESIST 1 and 2 clinical studies and analysis of a large hospital cohort (Marcelin et al 2007).
Saquinavir- fænotype ved baseline (skift i følsomhed i forhold til reference, PhenoSense Assay) har vist sig at være en forudsigelig faktor for virologisk resultat.
Baseline saquinavir phenotype (shift in susceptibility relative to reference, PhenoSense Assay) was shown to be a predictive factor of virological outcome.
Hvorimod der ikke blev observeret virologisk fordel, når ændringen var større end 12 gange.
Virological response was first observed to decrease when the fold shift exceeded 2.3-fold; whereas virological benefit was not observed when the fold shift exceeded 12-fold.
Marcelin et al (2007) identificerede ni proteasekodoner (L10F/ I/ M/ R/ V, I15A/ V, K20I/ M/ R/ T, L24I, I62V, G73S/ T, V82A/ F/ S/ T, I84V, L90M), som var forbundet med nedsat virologisk respons af saquinavir/ ritonavir (1000/ 100 mg to gange daglig) hos 138 saquinavir naive patienter.
Marcelin et al (2007) identified nine protease codons (L10F/ I/ M/ R/ V, I15A/ V, K20I/ M/ R/ T, L24I, I62V, G73S/ T, V82A/ F/ S/ T, I84V, L90M) that were associated with decreased virological response to saquinavir/ ritonavir (1000/ 100 mg twice daily) in 138 saquinavir naive patients.
Tilstedeværelse af 3 eller flere mutationer var forbundet med nedsat respons af saquinavir/ ritonavir.
The presence of 3 or more mutations was associated with reduced response to saquinavir/ ritonavir.
Sammenhængen mellem antallet af disse saquinavir- associerede resistensmutationer og det virologiske respons blev bekræftet i et uafhængigt klinisk studie (RESIST 1 og 2), som involverede en erfaringsmæssig stærkere behandlet patientpopulation, hvoraf 54% tidligere havde været behandlet med saquinavir (p=0, 0133, se tabel 3).
The association between the number of these saquinavir-associated resistance mutations and virological response was confirmed in an independent clinical study (RESIST 1 and 2) involving a more heavily treatment experienced patient population, including 54% who had received prior saquinavir (p=0.0133, see Table 3).
G48V- mutationen, som tidligere er blevet identificeret in vitro som saquinavirs signaturmutation, var til stede ved baseline i virus fra tre patienter, som ikke reagerede på behandlingen.
The G48V mutation, previously identified in vitro as a saquinavir signature mutation, was present at baseline in virus from three patients, none of whom responded to therapy.
Virologisk respons af saquinavir/ ritonavir indelt efter antallet af baseline saquinavir - associerede resistensmutationer.
Virological response to saquinavir/ ritonavir stratified by the number of baseline saquinavir- associated resistance mutations
RESIST 1 & 2 Marcelin et al (2007) SQV Naiv/ Tidligere behandlet
Marcelin et al (2007)
SQV Naiv
RESIST 1 & 2
population
Saquinavir Associated
population
SQV Naive Population
forbundne
SQV Naive/ Experienced Population
Ændring i
Resistance
Ændring i
Change in Baseline
baselineplasma
Change in Baseline
baselineplasma
Mutations
hiv- 1- RNA efter uger 12- 20
Plasma HIV-1 RNA at
hiv- 1- RNA efter uge 4
at Baseline*
* Saquinavir mutationsscore mutationer:
* Saquinavir Mutation Score Mutations:
I MaxCmin1- studiet, blev sikkerhed og effekt af saquinavir bløde kapsler/ ritonavir 1000/ 100 mg to gange daglig plus 2 NRTI/ Non- nukleosid reverse transkriptasehæmmere (NNRTI) sammenlignet med indinavir/ ritonavir 800/ 100 mg to gange daglig plus 2 NRTI/ NNRTI i over 300 patienter (både naive og tidligere proteasehæmmerebehandlede).
The combination of saquinavir and ritonavir
Kombinationen af saquinavir og ritonavir udviste større virologisk aktivitet i forhold til indinavir - og ritonavir- armen, når skift fra den oprindelige behandling blev regnet som virologisk svigt.
18 exhibited a superior virological activity compared with the indinavir and ritonavir arm when switch from the assigned treatment was counted as virological failure.
18 I MaxCmin2- studiet blev sikkerhed og effekt af saquinavir bløde kapsler/ ritonavir 1000/ 100 mg to gange daglig plus 2 NRTIs/ NNRTIs sammenlignet med lopinavir/ ritonavir 400/ 100 mg to gange daglig plus 2 NRTIs/ NNRTIs hos 324 patienter (både naive og tidligere proteasehæmmerebehandlede).
In the MaxCmin2 study, the safety and efficacy of saquinavir soft capsules/ ritonavir 1000/ 100 mg twice daily plus 2 NRTIs/ NNRTIs was compared with lopinavir/ ritonavir 400/ 100 mg twice daily plus 2 NRTIs/ NNRTIs in 324 (both protease inhibitor treatment naïve and experienced) subjects.
Ingen af patienterne i armen med lopinavir/ ritonavir havde været udsat for lopinavir før randomiseringen, mens 16 af patienterne i armen med saquinavir/ ritonavir havde tidligere været udsat for saquinavir.
None of the subjects in the lopinavir/ ritonavir arm had been exposed to lopinavir prior to randomisation whereas 16 of the subjects in the saquinavir/ ritonavir arm had previously been exposed to saquinavir.
Patientdemografiske karakteristika for MaxCmin1 og MaxCmin2 †
Subject Demographics MaxCmin1 and MaxCmin2 †
PI tidligere ubehandlede (%) Median baseline hiv- 1- RNA, log10 kopier/ ml (IQR) Median baseline CD4+ celletal, celler/ mm3 (IQR) data fra den kliniske studierapport
Male Race (White/Black/Asian)% Age, median, yrs CDC Category C (%) Antiretroviral naïve (%) PI naïve (%) Median Baseline HIV-1 RNA, log10 copies/ml (IQR) Median Baseline CD4+ Cell Count, cells/mm3 (IQR) data from clinical study report
41% 4, 0 (1, 7- 5, 1) 272 (135- 420)
82% 86/9/1 39 32% 28% 41% 4.0 (1.7-5.1) 272 (135-420)
38% 3, 9 (1, 7- 5, 2) 280 (139- 453)
74% 82/12/4 40 28% 22% 38% 3.9 (1.7-5.2) 280 (139-453)
48% 4, 4 (3, 1- 5, 1) 241 (86- 400)
81% 75/19/1 40 32% 31% 48% 4.4 (3.1-5.1) 241 (86-400)
48% 4, 6 (3, 5- 5, 3) 239 (95- 420)
76% 74/ 19/2 40 31% 34% 48% 4.6 (3.5-5.3) 239 (95-420)
Tabel 5:
19 Table 5:
Resultater ved uge 48 MaxCmin1 og MaxCmin2 †
Outcomes at Week 48 MaxCmin1 and MaxCmin2†
Påbegyndt tildelt behandling, n (%) Afbrudt tildelt behandling, n (%)
Initiated assigned treatment, n (%) Discontinued assigned treatment, n (%)
Virologisk svigt ITT/ e * #
Virological failure ITT/e*#
Andel med VL < 50 kopier/ ml ved uge 48, ITT/ e #
Proportion with VL < 50 copies/ml at week 48, ITT/e#
Andel med VL < 50 kopier/ ml ved uge 48, i behandling
Proportion with VL < 50 copies/ml at week 48, On Treatment
P=0, 48
P=0.48
Median stigning i CD4 celletal ved uge 48 (celler/ mm3)
Median increase in CD4 cell count at week 48 (cells/mm3)
* For begge studier:
* For both studies:
For patienter, der ved indgang i studiet havde VL < 200 kopier/ ml, er VF defineret som > 200 kopier/ ml.
For patients entering study with VL < 200 copies/ml, VF defined as > 200 copies/ml.
For patienter der indgik i studiet med VL > 200 kopier/ ml, er VF defineret som enhver stigning > 0, 5 logs og/ eller VL > 50. 000 kopies/ ml ved uge 4, > 5. 000 kopier/ ml ved uge 12, eller > 200 kopier/ ml ved uge 24 eller derefter.
For those entering with VL > 200 copies/ml, VF defined as any increase > 0.5 logs and/or VL > 50,000 copies/ml at week 4, > 5,000 copies/ml at week 12, or > 200 copies/ml at week 24 or thereafter.
19 hvis VL > 200 kopier/ ml ved uge 4; < 1, 0 log reduktion fra baseline hvis VL > 200 kopier/ ml ved uge 12; og VL > 200 kopier/ ml ved uge 24. # ITT/ e = Intent- to- treat/ exposed † Data fra den kliniske studierapport ‡ Data fra MaxCmin1 publikationen
MaxCmin2: any rise > 0.5 log at a specific visit; < 0.5 log reduction if VL > 200 copies/ml at week 4; < 1.0 log reduction from base line if VL > 200 copies/ml at week 12; and a VL > 200 copies/ml at week 24. # ITT/e = Intent-to-treat/exposed † Data from clinical study report ‡ Data from MaxCmin1 publication
Ritonavir hæmmer metaboliseringen af saquinavir og øger (” booster ”) derved plasmaniveauerne af saquinavir.
Ritonavir inhibits the metabolism of saquinavir, thereby increasing ("boosting") the plasma levels of saquinavir.
Absorption og biotilgængelighed hos voksne:
Absorption and bioavailability in adults:
Hos hiv- inficerede patienter, giver Invirase i kombination med ritonavir i doser på 1000/ 100 mg to gange daglig, en systemisk tilgængelighed af saquinavir over en 24- timers periode svarende til eller højere end opnåede værdier med saquinavir bløde kapsler 1200 mg tre gange daglig (se tabel 6).
In HIV-infected patients, Invirase in combination with ritonavir at doses of 1000/100 mg twice daily provides saquinavir systemic exposures over a 24-hour period similar to or greater than those achieved with saquinavir soft capsules 1200 mg tid (see Table 6).
Tabel 6:
20 Table 6:
Middel (% CV) - AUC, Cmax og Cmin af saquinavir hos patienter efter behandling med Invirase, saquinavir bløde kapsler, Invirase/ ritonavir og saquinavir bløde kapsler/ ritonavir i multiple doser
Mean (% CV) AUC, Cmax and Cmin of saquinavir in patients following multiple dosing of Invirase, saquinavir soft capsules, Invirase/ritonavir, and saquinavir soft capsules/ritonavir
AUCτ (ng· time/ ml)
AUCτ
AUC0- 24 (ng· time/ ml) †
AUC0-24
Invirase (hårde kapsler) 600 mg tre gange daglig
Invirase (hard capsule) 600 mg tid
saquinavir bløde kapsler 31 1200 mg tre gange daglig
saquinavir soft capsule 1200 mg tid
Invirase (tabletter)
Invirase (tablet)
10. 320
10,320
20. 640
20,640
1. 509
1509
1000 mg to gange dagligt plus ritonavir 100 mg to gange dagligt * (fastende)
1000 mg bid plus ritonavir 100 mg bid* (fasting condition)
(2. 530- 30. 327)
(2,530-30,327)
(355- 4. 101)
(355-4,101)
(70- 1. 725) ††
(70-1,725) ††
34. 926
34,926
69. 852
69,852
5. 208
5208
1. 179
1,179
1000 mg to gange dagligt plus ritonavir 100 mg to gange dagligt * (måltid med højt fedtindhold)
1000 mg bid plus ritonavir 100 mg bid* (high fat meal)
(11. 826- 105. 992)
(11,826- 105,992)
(1. 536- 14. 369) (334- 5. 176) ††
(334-5,176) ††
τ = doseringsinterval, dvs.
8 hour for tid
8 timer for dosering tre gange daglig og 12 timer for dosering to gange daglig Cmin = de observerede plasmakoncentrationer ved slutningen af dosisintervallet * resultaterne er geometriske gennemsnit (min – max) † afledt fra to eller tre gange daglig dosering †† Ctrough værdier
Cmin = the observed plasma concentration at the end of the dose interval bid = twice daily tid = three times daily * results are geometric mean (min - max) † derived from tid or bid dosing schedule †† Ctrough values
Absolut biotilgængelighed var i gennemsnit 4% (CV 73%, range:
Absolute bioavailability averaged 4% (CV 73%, range:
1% til 9%) hos 8 raske frivillige der fik en enkelt 600 mg dose (3 x 200 mg hårde kapsler) Invirase efter et stort morgenmåltid.
1% to 9%) in 8 healthy volunteers who received a single 600 mg dose (3 x 200 mg hard capsule) of Invirase following a heavy breakfast.
50 ng/ ml og en AUC0- 24 på omkring 20. 000 ng⋅time/ ml.
Effective therapy in treatment naïve patients is associated with a Cmin of approximately 50 ng/ml and an AUC0-24 of about 20,000 ng·h/ml.
100 ng/ ml og en AUC0- 24 på omkring 20. 000 ng⋅time/ ml.
Effective therapy in treatment experienced patients is associated with a Cmin of approximately 100 ng/ml and an AUC0-24 of about 20,000 ng·h/ml.
In vitro studier har vist, at saquinavir er et substrat for P- glycoprotein (P- gp).
In vitro studies have shown that saquinavir is a substrate for P-glycoprotein (P-gp).
Effekt af føde:
Effect of food:
Patienterne fik tre konsekutive doser under fastende betingelser eller efter et fedt - og kalorierigt måltid (46 g fedt, 1. 091 kcal), hvor AUC0- 12, Cmax og Ctrough værdier af saquinavir under fastende betingelser var omkring 70% lavere end efter et måltid med højt fedtindhold.
In a cross-over study in 22 HIV-infected patients treated with Invirase/ritonavir 1000 mg/100 mg twice daily and receiving three consecutive doses under fasting conditions or after a high-fat, high-calorie meal (46 g fat, 1,091 Kcal), the AUC0-12, Cmax and Ctrough values of saquinavir under fasting conditions were about 70 per cent lower than with a high-fat meal.
Alle undtagen én patient ramte Ctrough værdier for saquinavir over den terapeutiske grænseværdi (100 ng/ ml) under fastende betingelser.
All but one of the patients achieved Ctrough values of saquinavir above the therapeutic threshold (100 ng/ml) in the fasted state.
Der var ingen klinisk signifikante forskelle i den farmakokinetiske profil af ritonavir i fastende eller mæt tilstand, men ritonavir Ctrough (geometrisk gennemsnit 245 mod 348 ng/ ml) var lavere under fastende betingelser end efter indtagelse af et måltid.
348 ng/ml) was lower in the fasting state compared to the administration with a meal.
Invirase/ ritonavir kan administreres med eller uden samtidig fødeindtagelse.
Invirase/ritonavir should be administered with or after food.
Distribution hos voksne:
Distribution in adults:
Saquinavir penetrerer udtalt ind i vævene.
Saquinavir partitions extensively into the tissues.
Middel steady- state fordelingsvolumen efter intravenøs indgift af en 12 mg dosis af saquinavir var 700 l (CV 39%).
The mean steady-state volume of distribution following intravenous administration of a 12 mg dose of saquinavir was 700 l (CV 39%).
97% bundet til plasma proteiner op til 30 μg/ ml.
It has been shown that saquinavir is approximately 97% bound to plasma proteins up to 30 μg/ml.
Hos to patienter der fik Invirase 600 mg tre gange daglig fandtes cerebrospinalvæskekoncentrationerne af saquinavir ubetydelige sammenlignet med koncentrationer fra tilsvarende plasmaprøver.
In two patients receiving Invirase 600 mg three times daily, cerebrospinal fluid concentrations of saquinavir were negligible when compared to concentrations from matching plasma samples.
Metabolisme og udskillelse hos voksne:
21 Metabolism and elimination in adults:
In vitro eksperimenter har vist at saquinavir' s metabolisme er P450 medieret med det specifikke isoenzym, CYP3A4, som ansvarlig for over 90% af den hepatiske metabolisme.
In vitro studies using human liver microsomes have shown that the metabolism of saquinavir is cytochrome P450 mediated with the specific isoenzyme, CYP3A4, responsible for more than 90% of the hepatic metabolism.
Baseret på in vitro undersøgelser, metaboliseres saquinavir hurtigt til en række mono - og dihydroxylerede inaktive stoffer.
Based on in vitro studies, saquinavir is rapidly metabolised to a range of mono- and di-hydroxylated inactive compounds.
I en massebalanceundersøgelse med anvendelse af 600 mg 14 C- saquinavir (n = 8), genfandtes henholdsvis 88% og 1% af den peroralt indgivne radioaktivitet i fæces og i urin indenfor 4 døgn efter indgift.
In a mass bal ance study using 600 mg 14C-saquinavir (n = 8), 88% and 1% of the orally administered radioactivity, was recovered in faeces and urine, respectively, within 4 days of dosing.
Hos yderligere 4 personer der fik indgivet 10, 5 mg 14 C- saquinavir intravenøst, genfandtes henholdsvis 81% og 3% af den intravenøst indgivne radioaktivitet i fæces og i urin indenfor 4 døgn efter indgift.
In an additional four subjects administered 10.5 mg 14C-saquinavir intravenously, 81% and 3% of the intravenously administered radioactivity was recovered in faeces and urine, respectively, within 4 days of dosing.
13% af cirkulerende saquinavir i plasma fandtes som uomdannet aktivt stof efter peroral indgift og resten som metabolitter.
13% of circulating saquinavir in plasma was present as unchanged compound after oral administration and the remainder as metabolites.
Efter intravenøs indgift fandtes 66% af cirkulerende saquinavir som uomdannet aktivt stof og resten som metabolitter, hvilket tyder på at saquinavir undergår udtalt first pass metabolisme.
Following intravenous administration 66% of circulating saquinavir was present as unchanged compound and the remainder as metabolites, suggesting that saquinavir undergoes extensive first pass metabolism.
In vitro eksperimenter har vist at den hepatiske metabolisme af saquinavir mættes ved koncentrationer over 2 μg/ ml.
In vitro experiments have shown that the hepatic metabolism of saquinavir becomes saturable at concentrations above 2 μg/ml.
Systemisk clearance af saquinavir var høj, 1, 14 l/ h/ kg (CV 12%), lidt over leverens plasma - gennemstrømning og konstant efter intravenøse doser på 6, 36 og 72 mg.
Systemic clearance of saquinavir was high, 1.14 l/h/kg (CV 12%), slightly above the hepatic plasma flow, and constant after intravenous doses of 6, 36 and 72 mg.
Effekten af køn efter behandling med Invirase/ ritonavir:
Effect of gender following treatment with Invirase/ritonavir:
Der blev observeret en kønsforskel, idet kvinder havde højere saquinavireksponering end mænd (AUC gennemsnitligt 56% højere og Cmax gennemsnitligt 26% højere) i det bioækvivalensstudie, som sammenlignede Invirase 500 mg filmovertrukne tabletter med Invirase 200 mg hårde kapsler, i begge tilfælde i kombination med ritonavir.
A gender difference was observed with females showing higher saquinavir exposure than males (AUC on average 56% higher and Cmax on average 26% higher) in the bioequivalence study comparing Invirase 500 mg film coated tablets with Invirase 200 mg hard capsules both in combination with ritonavir.
Akut og kronisk toksicitet:
Acute and chronic toxicity:
Saquinavir blev udmærket tolereret i orale akutte og kroniske toksicitetsstudier på mus, rotter, hunde og silkeaber.
Saquinavir was well tolerated in oral acute and chronic toxicity studies in mice, rats, dogs and marmosets.
Mutagene og genotoksiske studier, med og uden relevant metabolisk aktivering, har vist, at saquinavir ikke har mutagen aktivitet in vitro i hverken bakterielle celler (Ames test) eller pattedyrsceller (kinesisk hamsterlunge V79/ HPRT- test).
Mutagenicity and genotoxicity studies, with and without metabolic activation where appropriate, have shown that saquinavir has no mutagenic activity in vitro in either bacterial (Ames test) or mammalian cells (Chinese hamster lung V79/HPRT test).
Saquinavir inducerer ikke kromosomale skader in vivo i en mikronukleus- test på mus eller in vitro i humane perifere blodlymfocytter.
Saquinavir does not induce chromosomal damage in vivo in the mouse micronucleus assay or in vitro in human peripheral blood lymphocytes and does not induce primary DNA damage in vitro in the unscheduled DNA synthesis test.
Der var ingen tegn på carcinogen aktivitet efter indgift af saquinavirmesilat i 96 til 104 uger til rotter og mus.
The re was no evidence of carcinogenic activity after the administration of saquinavir mesilate for 96 to 104 weeks to rats and mice.
Plasmakoncentrationerne (AUC- værdier) i rotter (maksimumdosis 1000 mg/ kg/ dag) og i mus (maksimumdosis 2500 mg/ kg/ dag) var lavere end de forventede plasmakoncentrationer, der blev opnået hos mennesker ved den anbefalede kliniske dosis af Invirase boostet med ritonavir.
The plasma exposures (AUC values) in rats (maximum dose 1000 mg/kg/day) and in mice (maximum dose 2500 mg/kg/day) were lower than the expected plasma exposures obtained in humans at the recommended clinical dose of ritonavir boosted Invirase.
Forplantningstoksicitet:
Reproductive toxicity: