natgillin/translations-raw huggingface dataset:
Tilstedeværelse af krydsresistens mod andre protease- hæmmere blev analyseret i 18 rebound- isolater, som havde vist udvikling af resistens mod lopinavir under 3 fase II - og et fase III - forsøg med Kaletra i protease - hæmmer- erfarne- patienter.
The presence of cross resistance to other protease inhibitors was analysed in 18 rebound isolates that had demonstrated evolution of resistance to lopinavir during 3 Phase II and one Phase III studies of Kaletra in protease inhibitor-experienced patients.
Den gennemsnitlige sammenlægning af IC50 for lopinavir for disse 18 isolater ved baseline og rebound var henholdsvis 6. 9 - og 63- gange sammenlignet med vildtype- virus.
The median fold IC50 of lopinavir for these 18 isolates at baseline and rebound was 6.9- and 63-fold, respectively, compared to wild type virus.
Der blev set beskedent fald i amprenavir- aktivitet med en gennemsnitlig stigning af IC50 fra 3. 7 – til 8- gange i henholdsvis baseline - og rebound- isolater.
Modest decreases in amprenavir activity were noted with a median increase of IC50 from 3.7- to 8-fold in the baseline and rebound isolates, respectively.
Isolaterne bibeholdt følsomhed for tipranavir med en gennemsnitlig stigning af IC50 i henholdsvis baseline - og rebound- isolater på 1. 9 - og 1. 8 gange, sammenlignet med vild- type virus.
Please refer to the Aptivus Summary of Product
Se venligt produktresuméet for Aptivis for yderligere information om anvendelsen af tipranavir, inklusiv genotype forudsigelse af respons, i behandling af lopinavir- resistent HIV- 1 - infektion.
16 Characteristics for additional information on the use of tipranavir, including genotypic predictors of response, in treatment of lopinavir-resistant HIV-1 infection.
Kaletras virkning (i kombination med andre antiretrovirale stoffer) på biologiske markører (plasma HIV RNA niveauer og CD4 celletælling) er blevet vurderet i en kontrolleret afprøvning af behandling med Kaletra i 24 uger og yderligere afprøvninger af behandling med Kaletra i 360 uger.
The effects of Kaletra (in combination with other antiretroviral agents) on biological markers (plasma HIV RNA levels and CD4 counts) have been investigated in a controlled study of Kaletra of 48 weeks duration, and in additional studies of Kaletra of 360 weeks duration.
Studie M98- 863 er en randomiseret, dobbeltblind afprøvning af Kaletra (400/ 100 mg to gange dagligt) i 653 patienter uden forudgående antiretroviral behandling sammenlignet med nelfinavir (750 mg tre gange dagligt) og nukleosid revers transkriptasehæmmere.
Study M98-863 is a randomised, double-blind trial of 653 antiretroviral treatment naïve patients investigating Kaletra (400/ 100 mg twice daily) compared to nelfinavir (750 mg three times daily) plus nucleoside reverse transcriptase inhibitors.
Ved ” intent- to- treat ” analyse, hvor patienter med manglende værdier bliver klassificeret som patienter, for hvem behandlingen har slået fejl, var andelen af patienter ved 48 uger med HIV RNA < 400 kopier/ ml 75% i Kaletra gruppen og 63% i nelfinavir gruppen efter 24 ugers behandling.
By intent to treat analysis where patients with missing values are considered virologic failures, the proportion of patients at 48 weeks with HIV RNA < 400 copies/ ml in the Kaletra arm was 75% and 63% in the nelfinavir arm.
Gennemsnitlig basal CD4 celletælling var 259 celler/ mm3 (variationsbredde:
Mean baseline CD4 cell count was 259 cells/ mm3 (range:
2 til 949 celler/ mm3) og gennemsnitlig basal plasma HIV- 1 RNA var 4, 9 log10 kopier/ ml (variationsbredde:
2 to 949 cells/ mm3) and mean baseline plasma HIV-1 RNA was 4.9 log10 copies/ ml (range:
2, 6 til 6, 8 log10 kopier/ ml).
2.6 to 6.8 log10 copies/ ml).
Ved 48 ugers behandling med Kaletra, havde 67% af patienterne plasma RNA < 50 kopier/ ml sammenlignet med 52% i nelfinavir gruppen.
Through 48 weeks of therapy, the proportion of patients in the Kaletra arm with plasma RNA < 50 copies/ ml was 67% and 52% in the nelfinavir arm.
Den gennemsnitlige stigning fra basal CD4 celletal var 207celler/ mm3 i Kaletra gruppen og 195 celler/ mm3 i nelfinavir gruppen.
The mean increase from baseline in CD4 cell count was 207 cells/ mm3 in the Kaletra arm and 195 cells/ mm3 in the nelfinavir arm.
Ved 48 ugers behandling havde en statistisk signifikant højere andel af patienterne i Kaletra armen HIV RNA < 50 kopier/ ml sammelignet med nelfinavir armen.
Through 48 weeks of therapy, a statistically significantly higher proportion of patients in the Kaletra arm had HIV RNA < 50 copies/ ml compared to the nelfinavir arm.
Et længerevarende virologisk respons er ligeledes observeret i et mindre fase II studie (M97- 720) efter 360 ugers behandling med Kaletra (i kombination med nukleosid/ nukleotid revers transkriptasehæmmere).
Sustained virological response to Kaletra (in combination with nucleoside/ nucleotide reverse transcriptase inhibitors) has been also observed in a small Phase II study (M97-720) through 360 weeks of treatment.
Et- hundrede patienter blev oprindeligt behandlet med Kaletra i forsøget (inkluderende 51 patienter, der modtog 400/ 100 mg to gange daglig og 49 patienter på enten 200/ 100 mg to gange daglig eller 400/ 200 to gange daglig).
One hundred patients were originally treated with Kaletra in the study (including 51 patients receiving 400/ 100 mg twice daily and 49 patients at either 200/ 100 mg twice daily or 400/ 200 mg twice daily).
Alle patienter på dosen 400/ 100 mg to gange daglig skiftede til open- label Kaletra mellem uge 48 og uge 72.
All patients converted to open-label Kaletra at the 400/ 100 mg twice daily dose between week 48 and week 72.
En- og- treds patienter fuldførte forsøget (35 patienter modtog den anbefaldede dosis 400/ 100 mg gennem hele forsøget).
Sixty-one patients completed the study (35 patients received the recommended 400/ 100 mg twice daily dose throughout the study).
Gennem 360 ugers behandling, var andelen af patieneter med HIV RNA < 400 (< 50) Kopier/ ml 61% (59%), og den korresponderende gennemsnitssigning i CD4 celletæling var 551 celler/ mm3.
Through 360 weeks of treatment, the proportion of patients with HIV RNA < 400 (< 50) copies/ ml was 61% (59%), and the corresponding mean increase in CD4 cell count was 501 cells/ mm3.
Niogtredve patienter (39%) afbrød studiet, inklusiv 16 (16%) som afbrød på grund af bivirkninger, en af dem var associeret med et dødsfald.
Thirty-nine patients (39%) discontinued the study, including 16 (16%) discontinuations due to adverse events, one of which was associated with a death.
Patienter med forudgående antiretroviral behandling
Patients with prior antiretroviral therapy
Studie M97- 765 er en randomiseret, dobbeltblind afprøvning af Kaletra i to dosisniveauer (400/ 100 mg og 400/ 200 mg, begge to gange dagligt) og nevirapin (200 mg to gange dagligt) og to nukleosid revers transkriptasehæmmere i 70 patienter, der tidligere er blevet behandlet med enkelt proteasehæmmere, men ikke med non- nukleosid revers transkriptasehæmmere.
Study M97-765 is a randomised, double-blind trial evaluating Kaletra at two dose levels (400/ 100 mg and 400/ 200 mg, both twice daily) plus nevirapine (200 mg twice daily) and two nucleoside reverse transcriptase inhibitors in 70 single protease inhibitor experienced, non-nucleoside reverse transcriptase inhibitor naïve patients.
72 til 807 celler/ mm3) og median basal plasma HIV- 1
Median baseline CD4 cell count was 349 cells/ mm3 (range 72 to 807 cells/ mm3) and median baseline plasma HIV-1 RNA was 4.0 log10 copies/ ml (range 2.9 to 5.8 log10 copies/ ml).
Ved ” intent- to- treat ” analyse, hvor patienter med manglende værdier bliver klassificeret som patienter, for hvem behandlingen har slået fejl, var andelen af patienter med HIV RNA < 400 (< 50) kopier/ ml efter 24 uger 75% (58%) og den gennemsnitlige stigning fra basal CD4 celletal var 174 celler/ mm3 hos de 36 patienter, der blev behandlet med Kaletra 400/ 100 mg.
By intent to treat analysis where patients with missing values are considered virologic failures, the proportion of patients with HIV RNA < 400 (< 50) copies/ ml at 24 weeks was 75% (58%) and the mean increase from baseline in CD4 cell count was 174 cells/ mm3 for the 36 patients receiving the 400/ 100 mg dose of Kaletra.
M98- 957 er en randomiseret, open- label afprøvning af Kaletra i to dosisniveauer (400/ 100 mg og 533/ 133 mg, begge to gange dagligt) og efavirenz (600 mg en gang dagligt) og nukleosid revers transkriptasehæmmere i 57 patienter, der tidligere er blevet behandlet med flere proteasehæmmere, men ikke med non- nukleosid revers transkriptasehæmmere.
M98-957 is a randomised, open-label study evaluating Kaletra treatment at two dose levels (400/ 100 mg and 533/ 133 mg, both twice daily) plus efavirenz (600 mg once daily) and nucleoside reverse transcriptase inhibitors in 57 multiple protease inhibitor experienced, non-nucleoside reverse transcriptase inhibitor naïve patients.
Mellem uge 24 og 48 blev patienter som var randomiseret til dosen 400/ 100 mg ændret til, en dosis på 533/ 133 mg.
Between week 24 and 48, patients randomised to a dose of 400/ 100 mg were converted to a dose of 533/ 133 mg.
Median basal CD4 celletal var 220 celler/ mm3 (variationsbredde:
Median baseline CD4 cell count was 220 cells/ mm3 (range 13 to 1030 cells/ mm3).
Ved ” intent- to- treat ” analyse af begge kombinerede doseringsgrupper (n=57), hvor patienter med manglende værdier bliver klassificeret som patienter, for hvem behandlingen har slået fejl, var andelen af patienter med HIV RNA < 400 kopier/ ml efter48 uger henholdsvis 65% og den gennemsnitlige stigning fra basal CD4 celletal var henholdsvis 94 celler/ mm3.
17 with HIV RNA < 400 copies/ ml at 48 weeks was 65% and the mean increase from baseline CD4 cell count was 94 cells/ mm3.
M98- 940 er en open- label afprøvning af en flydende formulering af Kaletra med 100 pædiatriske patienter, der enten var antiretroviralt behandlingsnaive (44%) eller med forudgående behandling med antiretrovirale midler (56%).
M98-940 is an open-label study of a liquid formulation of Kaletra in 100 antiretroviral naïve (44%) and experienced (56%) paediatric patients.
Ingen af patienterne var tidligere blevet behandlet med non- nukleosid revers transkriptasehæmmere.
All patients were non-nucleoside reverse transcriptase inhibitor naïve.
Patienterne blev randomiseret til enten 230 mg lopinavir/ 57, 5 mg ritonavir per m2 eller 300 mg lopinavir/ 75 mg ritonavir per m2.
Patients were randomised to either 230 mg lopinavir/ 57.5 mg ritonavir per m2 or 300 mg lopinavir/ 75 mg ritonavir per m2.
Derefter fortsatte alle patienter med 300/ 75 mg per m2.
Subsequently, all patients were continued on the 300/ 75 mg per m2 dose.
6 måneder til 12 år) og færre end 14% var under 2 år og 6 patienter var et år eller derunder.
Patients had a mean age of 5 years (range 6 months to 12 years) with 14 patients less than 2 years old and 6 patients one year or less.
Gennemsnitlig basal CD4 celletal var 838 celler/ mm3 og gennemsnitlig basal plasma HIV- 1 RNA var 4, 7 log10 kopier/ ml.
Mean baseline CD4 cell count was 838 cells/ mm3 and mean baseline plasma HIV-1 RNA was 4.7 log10 copies/ ml.
Ved 48 ugers behandling havde84% af de antiretroviralt behandlingsnaive patienter og 75% af de patienter med forudgående behandling med antiretrovirale midler HIV RNA < 400, og den gennemsnitlige stigninger fra basal CD4 celletal var henholdsvis 404 celler/ mm3 og 284 celler/ mm3.
Through 48 weeks of therapy, the proportion of patients with HIV RNA < 400 copies/ ml was 84% for antiretroviral naïve patients and 75% for antiretroviral experienced patients and the mean increases from baseline in CD4 cell count were 404 cells/ mm3 and 284 cells/ mm3 respectively.
Der var ingen betydelige forskelle mellem de to grupper.
The pharmacokinetic properties of lopinavir co-administered with ritonavir have been evaluated in healthy adult volunteers and in HIV-infected patients; no substantial differences were observed between the two groups.
I forskellige afprøvninger af HIV- smittede patienter ses det, at Kaletra 400/ 100 mg to gange dagligt forårsager gennemsnitlige steady- state lopinavir plasmakoncentrationer, der er 15 til 20 gange højere end ritonavir.
Across studies, administration of Kaletra 400/ 100 mg twice daily yields mean steady-state lopinavir plasma concentrations 15 to 20-fold higher than those of ritonavir in HIV-infected patients.
Plasmaniveauerne af ritonavir er mindre end 7% af hvad, der opnås efter en ritonavir dosis på 600 mg to gange dagligt.
The plasma levels of ritonavir are less than 7% of those obtained after the ritonavir dose of 600 mg twice daily.
Flergangsdosering med 400/ 100 mg Kaletra to gange dagligt i 3- 4 uger og uden begrænsning af fødeindtagelse forårsager en gennemsnitlig ± SD lopinavir maksimal plasmakoncentration (Cmax) på 9, 6 ± 4, 4 μg/ ml, der fremkommer cirka 4 timer efter administration.
Absorption: multiple dosing with 400/ 100 mg Kaletra twice daily for 3 to 4 weeks and without meal restriction produced a mean ± SD lopinavir peak plasma concentration (Cmax) of 9.6 ± 4.4 μ g/ ml, occurring approximately 4 hours after administration.
Den gennemsnitlige laveste steady- state koncentration før morgen dosis var 5, 5 ± 4, 0 μg/ ml.
The mean steady-state trough concentration prior to the morning dose was 5.5 ± 4.0 μ g/ ml.
Lopinavir AUC over et 12 timers doseringsinterval var i gennemsnit 82, 8 ± 44, 5 μg• h/ ml.
Lopinavir AUC over a 12 hour dosing interval averaged 82.8 ± 44.5 μ g• h/ ml.
Fødeindtagelse og dets effekter på oral absorption:
Effects of food on oral absorption:
Kaletra bløde kapsler og Kaletra oral opløsning er bioækvivalente under ikke- fastende betingelser (mad med moderat fedtindhold).
Kaletra soft capsules and liquid have been shown to be bioequivalent under nonfasting conditions (moderate fat meal).
Indtag af en enkelt 400/ 100 mg dosis af Kaletra bløde kapsler og et måltid med moderat fedtindhold (500 - 682 kcal, 22, 7 - 25, 1% fra fedt) var forbundet med en gennemsnitlig stigning på 48% og 23% for henholdsvis
Administration of a single 400/ 100 mg dose of Kaletra soft capsules with a moderate fat meal (500 – 682 kcal, 22.7 – 25.1% from fat) was associated with a mean increase of 48% and 23% in lopinavir AUC and Cmax, respectively, relative to fasting.
For Kaletra oral opløsning er de tilsvarende stigninger i AUC og Cmax henholdsvis 80 og 54%.
For Kaletra oral solution, the corresponding increases in lopinavir AUC and Cmax were 80% and 54%, respectively.
Administration af Kaletra og et måltid med højt fedtindhold (872 kcal, 55, 8% fra fedt) øgede lopinavir AUC og Cmax med henholdsvis 96 og 43% for bløde kapsler og henholdsvis 130 og 56% for den orale opløsning.
Administration of Kaletra with a high fat meal (872 kcal, 55.8% from fat) increased lopinavir AUC and Cmax by 96% and 43%, respectively, for soft capsules, and 130% and 56%, respectively, for oral solution.
Ved steady- state er lopinavir cirka 98- 99% bundet til serumproteiner.
Distribution: at steady state, lopinavir is approximately 98 − 99% bound to serum proteins.
Lopinavir bindes både til alfa- 1- syre glucoprotein (AAG) og albumin, men har støre affinitet overfor AAG.
Lopinavir binds to both alpha-1-acid glycoprotein (AAG) and albumin, however, it has a higher affinity for AAG.
Ved steady - state forbliver lopinavir proteinbinding konstant, ved en række observerede koncentrationer, efter 400/ 100 mg Kaletra to gange dagligt, og den er sammenlignelig mellem raske frivillige og HIV - positive patienter.
At steady state, lopinavir protein binding remains constant over the range of observed concentrations after 400/ 100 mg Kaletra twice daily, and is similar between healthy volunteers and HIV-positive patients.
In vitro forsøg med human hepatiske mikrosomer indikerer at lopinavir fortrinsvis metaboliseres oxidativt.
Metabolism: in vitro experiments with human hepatic microsomes indicate that lopinavir primarily undergoes oxidative metabolism.
Lopinavir er i høj grad metaboliseret af det hepatiske cytokrom- P450 system, næsten udelukkende af isoenzym CYP3A.
Lopinavir is extensively metabolised by the hepatic cytochrome P450 system, almost exclusively by isozyme CYP3A.
Ritonavir er en potent CYP3A- hæmmer, hvilket hæmmer metabolismen af lopinavir og derved øger plasma niveauer af lopinavir.
18 inhibits the metabolism of lopinavir and therefore, increases plasma levels of lopinavir.
En afprøvning i mennesker med 14C- lopinavir har vist at 89% af plasmaradioaktiviteten efter en enkelt 400/ 100 mg Kaletra dosis skyldes den aktive modersubstans.
A 14 C-lopinavir study in humans showed that 89% of the plasma radioactivity after a single 400/ 100 mg Kaletra dose was due to parent active substance.
4 - oxo - og 4- hydroxymetabolit epimere par er de primære metabolitter med antiviral effekt, men de udgør kun en lille del af den samlede plasmaradioaktivitet.
The 4-oxo and 4-hydroxymetabolite epimeric pair are the major metabolites with antiviral activity, but comprise only minute amounts of total plasma radioactivity.
Efter en dosis 400/ 100 mg 14C- lopinavir/ ritonavir kan cirka 10, 4 ± 2, 3% og 82, 6 ± 2, 5% af den indgivne dosis genfindes henholdsvis i urin og fæces.
Elimination: after a 400/ 100 mg 14C-lopinavir/ ritonavir dose, approximately 10.4 ± 2.3% and 82.6 ± 2.5% of an administered dose of 14C-lopinavir can be accounted for in urine and faeces, respectively.
Uændret lopinavir udgjorde cirka 2, 2% og 19, 8% af den indgivne dosis i henholdsvis urin og fæces.
Unchanged lopinavir accounted for approximately 2.2% and 19.8% of the administered dose in urine and faeces, respectively.
Efter flergangsdosering bliver mindre end 3% af lopinavir dosis udskilt uændret i urinen.
After multiple dosing, less than 3% of the lopinavir dose is excreted unchanged in the urine.
Lopinavirs effektive halveringstid (fra maksimum til minimum) over et doseringsinterval på 12 timer er i gennemsnit 5- 6 timer, og lopinavirs tilsyneladende orale clearance (CL/ F) er 6 til 7 l/ h.
The effective (peak to trough) half-life of lopinavir over a 12 hour dosing interval averaged 5 − 6 hours, and the apparent oral clearance (CL/ F) of lopinavir is 6 to 7 l/ h.
Pædiatriske patienter:
Paediatrics:
Farmakokinetiske parametre af Kaletra 300/ 75 mg/ m2 to gange dagligt og 230/ 57, 5 mg/ m2 to gange dagligt er blevet undersøgt på i alt 53 pædiatriske patienter i alderen fra 6 måneder til 12 år.
The pharmacokinetics of Kaletra 300/ 75 mg/ m2 twice daily and 230/ 57.5 mg/ m2 twice daily have been studied in a total of 53 paediatric patients, ranging in age from 6 months to 12 years.
Lopinavir gennemsnitlig steady- state AUC, Cmax og Cmin var henholdsvis 72, 6 ± 31, 1 μg• h/ ml, 8, 2 ± 2, 9 μg/ ml og 3, 4 ± 2, 1 μg/ ml efter Kaletra 230/ 57, 5 mg/ m2 to gange dagligt uden nevirapin (n=12) og var henholdsvis 85, 8 ± 36, 9 μg• h/ ml, 10, 0 ± 3, 3 μg/ ml og 3, 6 ± 3, 5 μg/ ml efter 300/ 75 mg/ m2 to gange dagligt med nevirapin (n=12).
The lopinavir mean steady-state AUC, Cmax, and Cmin were 72.6 ± 31.1 μ g• h/ ml, 8.2 ± 2.9 μ g/ ml and 3.4 ± 2.1 μ g/ ml, respectively after Kaletra 230/ 57.5 mg/ m2 twice daily without nevirapine (n=12), and were 85.8 ± 36.9 μ g• h/ ml, 10.0 ± 3.3 μ g/ ml and 3.6 ± 3.5 μ g/ ml, respectively after 300/ 75 mg/ m2 twice daily with nevirapine (n=12).
Behandling med 230/ 57, 5 mg/ m2 to gange dagligt uden nevirapin og 300/ 75 mg/ m2 to gange dagligt med nevirapin gav lopinavir plasmakoncentrationer, der var sammenlignelige med de plasmakoncentrationer, der blev påvist i voksne efter indtagelse af 400/ 100 mg to gange dagligt uden nevirapin.
The 230/ 57.5 mg/ m2 twice daily regimen without nevirapine and the 300/ 75 mg/ m2 twice daily regimen with nevirapine provided lopinavir plasma concentrations similar to those obtained in adult patients receiving the 400/ 100 mg twice daily regimen without nevirapine.
Kaletra bløde kapsler og Kaletra oral opløsning er bioækvivalente under ikke- fastende betingelser.
Kaletra soft capsules and Kaletra oral solution are bioequivalent under nonfasting conditions.
Køn, race og alder:
Gender, Race and Age:
Farmakokinetiske parametre af Kaletra er ikke blevet undersøgt hos ældre personer.
Kaletra pharmacokinetics have not been studied in the elderly.
20 Nyreinsufficiens:
Renal Insufficiency:
Steady state farmakokinetiske parametre for lopinavir hos HIV- inficerede patienter med mild til moderet svækket leverfunktion blev sammelignet med de HIV- inficerede patienter med normal leverfunktion i et multidosis studie med lopinavir/ ritonavir 400/ 100 mg to gange daglig.
The steady state pharmacokinetic parameters of lopinavir in HIV-infected patients with mild to moderate hepatic impairment were compared with those of HIV-infected patients with normal hepatic function in a multiple dose study with lopinavir/ ritonavir 400/ 100 mg twice daily.
4. 2).
A limited increase in total lopinavir concentrations of approximately 30% has been observed which is not expected to be of clinical relevance (see section 4.2).
Toksicitetsforsøg med gentagen indgift i gnavere og hunde har påvist de vigtigste målorganer som værende lever, nyre, thyreoidea, milten og cirkulerende røde blodceller.
Repeat-dose toxicity studies in rodents and dogs identified major target organs as the liver, kidney, thyroid, spleen and circulating red blood cells.
Mens den eksponering, der gav disse forandringer var sammenlignelige med eller under den kliniske eksponering i mennesker, var doseringen i dyr over 6 gange den anbefalede kliniske dosering.
Mild renal tubular
Let renal tubular degenerering blev udelukkende observeret i mus, der blev eksponeret til mindst to gange den anbefalede humane eksponering, nyrene var upåvirkede i rotter og hunde.
19 degeneration was confined to mice exposed with at least twice the recommended human exposure; the kidney was unaffected in rats and dogs.
Nedsat serum thyroxin forårsagede en stigning i frigivelse af TSH med efterfølgende follikulær celle hypertrofi i skjoldbruskkirtlerne hos rotter.
Reduced serum thyroxine led to an increased release of TSH with resultant follicular cell hypertrophy in the thyroid glands of rats.
Coombs- negative anisocytose og poikilocystose var observeret hos rotter, men ikke i mus eller hunde.
Coombs-negative anisocytosis and poikilocytosis were observed in rats, but not in mice or dogs.
I In vitro studier blev klonede humane kardiale kalium kanaler (HERG) inhiberet 30% af de højeste testede koncentrationer af lopinavir/ ritanovir, svarende til en lopinavir eksponering på 7 gange det totale og 15 gange det frie peak plasma niveau, som opnås i mennesker ved de maksimalt anbefalede doser.
During in vitro studies, cloned human cardiac potassium channels (HERG) were inhibited by 30% at the highest concentrations of lopinavir/ ritonavir tested, corresponding to a lopinavir exposure 7-fold total and 15-fold free peak plasma levels achieved in humans at the maximum recommended therapeutic dose.
Der blev derimod ved lignende koncentrationer ikke demonstreret nogen repolariserings forsinkelse på kanin hjerte Purkinje fibre.
In contrast, similar concentrations of lopinavir/ ritonavir demonstrated no repolarisation delay in the canine cardiac Purkinje fibres.
Lavere koncentrationer af lopinavir/ ritonavir gav ikke nogen signifikant kalium (HERG) strøm blokade.
Lower concentrations of lopinavir/ ritonavir did not produce significant potassium (HERG) current blockade.
50% af den målte plasma AUC.
Tissue distribution studies conducted in the rat did not suggest significant cardiac retention of the active substance; 72-hour AUC in heart was approximately 50% of measured plasma AUC.
Tydelige U- bølger på elektrokardiogrammet er blevet observeret i hunde i forbindelse med forlænget PR- interval og bradycardia.
In dogs, prominent U waves on the electrocardiogram have been observed associated with prolonged PR interval and bradycardia.
4. 8 Bivirkninger).
These effects have been assumed to be caused by electrolyte disturbance The clinical relevance of these preclinical data is unknown, however, the potential cardiac effects of this product in humans cannot be ruled out (see also sections 4.4 and 4.8).