natgillin/translations-raw huggingface dataset:
Systemic corticosteroid effects including Cushing's syndrome and adrenal suppression have been reported in patients receiving ritonavir and inhaled or intranasally administered fluticasone propionate; this could also occur with other corticosteroids metabolised via the P450 3A pathway eg budesonide.
Pri bolnikih, ki so prejemali ritonavir in inhalacijske ali intranazalne oblike flutikazonpropionata, so poročali o pojavu sistemskih kortikosteroidnih učinkov, vključno s Cushingovim sindromom in z zaviralnim vplivom na nadledvičo žlezo.
Consequently, concomitant administration of Kaletra and these glucocorticoids is not recommended unless the potential benefit of treatment outweighs the risk of systemic corticosteroid effects (see section 4.4).
Omenjeni sistemski kortikosteroidni učinki se lahko pojavijo tudi pri uporabi drugih kortikosteroidov, ki se presnavljajo s P450 3A, npr. budezonid, zato sočasne uporabe zdravila Kaletra in tovrstnih glukokortikodov ne priporočamo, razen v primerih, ko možne koristi zdravljenja prevladajo nad tveganjem za pojav sistemskih kortikosteroidnih učinkov (glejte poglavje 4. 4).
A dose reduction of the glucocorticoid should be considered with close monitoring of local and systemic effects or a switch to a glucocorticoid, which is not a substrate for CYP3A4 (eg beclomethasone).
Razmisliti je treba o zmanjšanju odmerka glukokortikoidov ob sočasnem skrbnem nadziranju lokalnih in sistemskih učinkov ali o zamenjavi z glukokortikoidom, ki ni substrat za CYP3A4 (npr. beklometazon).
Studies in rats revealed that lopinavir is excreted in the milk.
54 Študije pri podganah so pokazale, da se lopinavir izloča v mleku.
52 4.8 Undesirable effects
4. 8 Neželeni učinki
The safety of Kaletra has been investigated in 612 patients in Phase II/ III clinical trials, of which 442 have received a dose of 400/ 100 mg twice daily.
Varnost zdravila Kaletra so raziskali pri 612 bolnikih v kliničnih preskušanjih II. in III. faze; 442 teh bolnikov je dobivalo odmerek 400/ 100 mg dvakrat na dan.
The most common adverse reaction associated with Kaletra therapy was diarrhoea and was generally of mild to moderate severity.
Najpogostejši neželen učinek, povezan z zdravljenjem z zdravilom Kaletra, je bila driska, ki je bila praviloma blaga do zmerna.
53 Undesirable effects in clinical studies in adult patients Infections and infestations
Infekcijske in parazitske bolezni
Otitis media, bronchitis, sinusitis, furunculosis, bacterial infection, viral infection
vnetje srednjega ušesa, bronhitis, sinuzitis, furunkuloza, bakterijska okužba, virusna okužba
Avitaminosis, dehydration, oedema, increased appetite, lactic acidosis, obesity, anorexia, diabetes mellitus, hyperglycaemia, hypocholesteremia
avitaminoza, dehidracija, edemi, zvečan apetit, laktacidoza, debelost, anoreksija, diabetes mellitus, hiperglikemija, hipoholesteremija
Headache, paresthesia
glavobol, parastezija
Dizziness, amnesia, ataxia, encephalopathy, facial paralysis, hypertonia, neuropathy, peripheral neuritis, somnolence, tremor, taste loss, taste perversion, migraine, extrapyramidal syndrome
omotica, amnezija, ataksija, encefalopatija, paraliza obraza, hipertonija, nevropatija, periferni nevritis, zaspanost, tremor, izguba okusa, motnje okusa, migrena, ekstrapiramidni sindrom
Abnormal vision, eye disorder Tinnitus Palpitation, lung oedema, myocardial infarct1 Hypertension, thrombophlebitis, vasculitis, varicose vein, deep thrombophlebitis, vascular disorder
hipertenzija, tromboflebitis, vaskulitis, varikozne vene, globoka flebotromboza, žilna motnja
Gastrointestinal disorders
56 Bolezni prebavil
54 Skin and subcutaneous tissue disorders
Bolezni kože in podkožja
Kidney calculus, urine abnormality, albuminuria, hypercalcinuria, nephritis, hyperuricemia
ledvični kamni, nenormalnosti urina, albuminurija, hiperkalciurija, nefritis, hiperurikemija
Abnormal ejaculation, amenorrhoea, breast enlargement, gynecomastia, impotence, menorrhagia
nenormalna ejakulacija, amenoreja, zvečanje prsi, ginekomastija, impotenca, menoragija
SGOT/ AST, increased SGPT/ ALT, liver function tests abnormal
zvišana glukoza, zvišana amilaza, zvišana SGOT/ AST, zvišana SGPT/ ALT, nenormalni jetrni funkcijski testi
weight loss, increased bilirubin, hormone level altered, lab test abnormal
Test
55 Paediatric patients
57 Pediatrični bolniki
Since Kaletra is highly protein bound, dialysis is unlikely to be beneficial in significant removal of the active substance.
Ker je zdravilo Kaletra v veliki meri vezana na beljakovine, ni verjetno, da bi dializa pomembno odstranila zdravilno učinkovino.
Antiviral activity in vitro: the in vitro antiviral activity of lopinavir against laboratory and clinical HIV strains was evaluated in acutely infected lymphoblastic cell lines and peripheral blood lymphocytes, respectively.
V odsotnosti človeškega seruma je bila povprečna IC50 lopinavirja proti petim različnim laboratorijskim sevom HIV- 1 19 nM.
In the absence of human serum, the mean IC50 of lopinavir against five different HIV-1 laboratory strains was 19 nM.
V odsotnosti oz. prisotnosti 50% človeškega seruma je bila povprečna IC50 lopinavirja proti HIV- 1IIIB v celicah MT4 17 nM oz.
Resistance
In vitro selekcija odpornosti:
In vitro selection of resistance:
Izolati HIV- 1 z zmanjšano občutljivostjo za lopinavir so bili izbrani in vitro.
HIV-1 isolates with reduced susceptibility to lopinavir have been selected in vitro.
Analiza odpornosti pri bolnikih, naivnih za protiretrovirusna zdravila:
HIV-1 has been passaged in vitro with lopinavir alone and with lopinavir plus ritonavir at concentration ratios representing the range of plasma concentration ratios observed during Kaletra therapy.
V študiji II. faze (M97- 720) so med 204 tedni zdravljenja uspešno opravili genotipsko analizo virusnih izolatov pri 11 od 16 bolnikov s potrjeno HIV RNA nad 400 kopij/ ml.
Genotypic and phenotypic analysis of viruses selected in these passages suggest that the presence of ritonavir, at these concentration ratios, does not measurably influence the selection of lopinavir-resistant viruses.
Analiza ni pokazala primarnih mutacij oz. mutacij aktivnega mesta na proteazi (aminokisline na položajih 8, 30, 32, 46, 47, 48, 50, 82, 84 in 90) ali fenotipske odpornosti proti zaviralcu proteaze.
In a Phase II study (M97-720) through 204 weeks of treatment, genotypic analysis of viral isolates was successfully conducted in 11 of 16 patients with confirmed HIV RNA above 400 copies/ ml revealed no primary or active site mutations in protease (amino acids at positions 8, 30, 32, 46, 47, 48, 50, 82, 84 and 90) or protease inhibitor phenotypic resistance.
59 V študiji III. faze (M98- 863) so 653 bolnikov randomizirali na prejemanje stavudina in lamivudina z bodisi lopinavirjem/ ritonavirjem ali nelfinavirjem.
57 subjects could be amplified for resistance testing.
Analiza odpornosti pri bolnikih, izkušenih z zaviralci proteaz:
Resistance to nelfinavir, defined as the presence of the D30N or L90M mutation in protease, was observed in 41/ 96 (43%) subjects.
Selekcijo odpornosti proti lopinavirju pri bolnikih, pri katerih je bilo predhodno zdravljenje z zaviralcem proteaz neuspešno, so opredelili z analizo longitudinalnih izolatov 19 bolnikov, izkušenih z zaviralci proteaz, in sicer v dveh študijah II. faze in eni študiji III. faze.
Resistance to lopinavir, defined as the presence of any primary or active site mutations in protease (see above), was observed in 0/ 51 (0%) subjects.
Pri teh bolnikih se je po uvodnem odzivu na zdravilo Kaletra pojavila bodisi nepopolna virološka supresija ali virusni preobrat, poleg tega se je pri njih kazala naraščajoča odpornost in vitro med izhodiščem in preobratom (opredeljenim kot pojav novih mutacij ali 2- kratna sprememba fenotipske občutljivosti za lopinavir).
Lack of resistance to lopinavir was confirmed by phenotypic analysis.
Najpogosteje so se pojavile mutacije V82A, I54V in M46I.
Analysis of resistance in PI-experienced patients:
Opažali so tudi mutacije L33F, I50V in V32I v kombinaciji z I47V/ A.
The selection of resistance to lopinavir in patients having failed prior protease inhibitor therapy was characterised by analysing the longitudinal isolates from 19 protease inhibitor-experienced subjects in 2 Phase II and one Phase III studies who either experienced incomplete virologic suppression or viral rebound subsequent to initial response to Kaletra and who demonstrated incremental in vitro resistance between baseline and rebound (defined as emergence of new mutations or 2-fold change in phenotypic susceptibility to lopinavir).
In vitro so ocenili protivirusno dejavnost lopinavirja proti 112 kliničnim izolatom, vzetih bolnikom, pri katerih zdravljenje z enim ali več zaviralci proteaz ni bilo uspešno.
Incremental resistance was most common in subjects whose baseline isolates had several protease inhibitor-associated mutations, but < 40-fold reduced susceptibility to lopinavir at baseline.
V tem okviru so bile z manjšo občutljivostjo za lopinavir in vitro povezane naslednje mutacije proteaze HIV:
Mutations V82A, I54V and M46I emerged most frequently.
L10F/ I/ R/ V, K20M/ R, L24I, M46I/ L, F53L, I54L/ T/ V, L63P, A71I/ L/ T/ V, V82A/ F/ T, I84V in L90M.
Mutations L33F, I50V and V32I combined with I47V/ A were also observed.
Mediana EC50 lopinavirja proti izolatom z 0– 3, 4– 5, 6– 7 oz.
The 19 isolates demonstrated a 4.3-fold increase in IC50 compared to baseline isolates (from 6.2- to 43-fold, compared to wild-type virus).
8– 10 mutacijami na omenjenih aminokislinskih položajih je bila 0, 8 -, 2, 7 -, 13, 5 - oz.
Genotypic correlates of reduced phenotypic susceptibility to lopinavir in viruses selected by other protease inhibitors.
44, 0- krat večja kot EC50 proti divjemu tipu HIV.
Within this panel, the following mutations in HIV protease were associated with reduced in vitro susceptibility to lopinavir:
Vseh 16 virusov, ki so pokazali > 20- kratno spremembo v občutljivosti, je imelo mutacije na položajih 10, 54, 63 ter dodatno 82 in/ ali 84.
L10F/ I/ R/ V, K20M/ R, L24I, M46I/ L, F53L, I54L/ T/ V, L63P, A71I/ L/ T/ V, V82A/ F/ T, I84V and L90M.
Poleg tega so imeli mediano 3 mutacije na aminokislinskih položajih 20, 24, 46, 53, 71 in 90.
The median EC50 of lopinavir against isolates with 0 − 3, 4 − 5, 6 − 7 and 8 − 10 mutations at the above amino acid positions was 0.8, 2.7 13.5 and 44.0-fold higher than the EC50 against wild type HIV, respectively.
Poleg zgoraj opisanih mutacij so opažali mutaciji V32I in I47A pri izolatih s preobratom, to je z manjšo občutljivostjo za lopinavir pri bolnikih izkušenih z zaviralci proteaz, ki so dobivali zdravilo Kaletra.
The 16 viruses that displayed > 20-fold change in susceptibility all contained mutations at positions 10, 54, 63 plus 82 and/ or 84.
Pri izolatih s preobratom, to je z manjšo občutljivostjo za lopinavir pri bolnikih, ki so dobivali zdravilo Kaletra, so opažali tudi mutaciji I47A in L76V.
In addition to the mutations described above, mutations V32I and I47A have been observed in rebound isolates with reduced lopinavir susceptibility from protease inhibitor experienced patients receiving Kaletra therapy.
Zaključki o pomembnosti določenih mutacij ali mutacijskih vzorcev se lahko spreminjajo z dodatnimi podatki, zato je priporočljivo, da se vedno upošteva trenutne sisteme interpretacije za analiziranje rezultatov preizkusa odpornosti.
After 48 weeks of treatment with Kaletra, efavirenz and nucleoside reverse transcriptase inhibitors, plasma HIV RNA ≤ 400 copies/ ml was observed in 93% (25/ 27), 73% (11/ 15), and 25% (2/ 8) of patients with< 10-fold, 10 to 40-fold, and > 40-fold reduced susceptibility to lopinavir at baseline, respectively.
33% (2/ 6) bolnikov z 0– 5, 6– 7 oz.
In addition, virologic response was observed in 91% (21/ 23), 71% (15/ 21) and 33% (2/ 6) patients with 0 − 5, 6 − 7, and 8 − 10 mutations of the above mutations in HIV protease associated with reduced in vitro susceptibility to lopinavir.
Ker ti bolniki predhodno niso bili izpostavljeni niti zdravilu Kaletra niti efavirenzu,
Since these patients had not previously been exposed to either Kaletra or efavirenz, part of the response may be attributed to the antiviral activity of efavirenz, particularly in patients harbouring highly lopinavir resistant virus.
60 je del odziva mogoče pripisati protivirusni dejavnosti efavirenza, zlasti pri bolnikih, ki so imeli proti lopinavirju zelo odporen virus.
Please refer to the Aptivus Summary of Product
Klinični farmakodinamični podatki
58 Characteristics for additional information on the use of tipranavir, including genotypic predictors of response, in treatment of lopinavir-resistant HIV-1 infection.
Učinke zdravila Kaletra (v kombinaciji z drugimi protiretrovirusnimi zdravili) na biološke označevalce (koncentracijo HIV RNA in število celic CD4 v plazmi) so raziskali v kontrolirani 48- tedenski študiji zdravila Kaletra ter v dodatnih 360- tedenskih raziskavah zdravila Kaletra.
Clinical pharmacodynamic data
Uporaba pri odraslih
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.
Povprečno izhodiščno število celic CD4 je bilo 259 celic/ mm3 (razpon: od 2 do 949 celic/ mm3), povprečna izhodiščna HIV- 1 RNA v plazmi pa je bila 4, 9 log10 izvodov/ ml (razpon: od 2, 6 do 6, 8 log10 izvodov/ ml).
Patients without prior antiretroviral therapy
Med 48 tedni zdravljenja je bil delež bolnikov z RNA v plazmi < 50 izvodov/ ml v kraku z zdravilom Kaletra 67% in v kraku z nelfinavirjem 52%.
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.
Dolgotrajni virološki odziv na zdravilo Kaletra (v kombinaciji z nukleozidnimi/ nukleotidnimi zaviralci reverzne transkriptaze) so ugotovili tudi v majhni študiji II. faze (M97- 720) med 360 tedni zdravljenja.
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.
Uvodoma je zdravilo Kaletra v študiji dobivalo 100 bolnikov (51 bolnikov je dobivalo odmerek 400/ 100 mg dvakrat na dan, 49 bolnikov pa bodisi 200/ 100 mg dvakrat na dan ali 400/ 200 mg dvakrat na dan).
Mean baseline CD4 cell count was 259 cells/ mm3 (range:
Vsi bolniki so med 48. in 72. tednom prešli na odprto uporabo zdravila Kaletra v odmerku 400/ 100 mg dvakrat na dan.
2.6 to 6.8 log10 copies/ ml).
Študijo je dokončalo 61 bolnikov (35 bolnikov je ves čas študije dobivalo priporočeni odmerek 400/ 100 mg dvakrat na dan).
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.
Med 360 tedni zdravljenja je bil delež bolnikov s HIV RNA < 400 (< 50) izvodov/ ml 61% (59%) in ustrezajoči povprečni porast CD4 celic 501 celic/ mm3.
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.
Devetintrideset bolnikov (39%) je prenehalo s študijo, vključno s 16 (16%) prenehanji zaradi neželenih dogodkov, eden izmed teh je bil povezan s smrtjo.
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.
Študija M97- 765 je randomizirano, dvojno slepo preskušanje za oceno zdravila Kaletra v dveh različnih odmerkih (400/ 100 mg in 400/ 200 mg, oboje dvakrat na dan) hkrati z nevirapinom (200 mg
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.
Mediano izhodiščno število celic CD4 je bilo 349 celic/ mm3 (razpon od 72 do 807 celic/ mm3) in mediana izhodiščna HIV- 1 RNA v plazmi je bila 4, 0 log10 izvodov/ ml (razpon od 2, 9 do 5, 8 log10 izvodov/ ml).
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).
Po analizi z namenom zdravljenja, pri kateri so bili bolniki z manjkajočimi podatki obravnavani kot virološki neuspeh, sta bila delež bolnikov s HIV RNA < 400 izvodov/ ml po 24 tednih 75% (58%) in povprečno zvečanje števila celic CD4 od izhodišča 174 celic/ mm3 za 36 bolnikov, ki so dobivali zdravilo Kaletra v odmerku 400/ 100 mg.
All patients converted to open-label Kaletra at the 400/ 100 mg twice daily dose between week 48 and week 72.
M98- 957 je randomizirana, odprta študija za oceno zdravljenja z zdravilom Kaletra v dveh različnih odmerkih (400/ 100 mg in 533/ 133 mg, oboje dvakrat na dan) hkrati z efavirenzem (600 mg enkrat na dan) ter nukleozidnimi zaviralci reverzne transkriptaze pri 57 bolnikih, izkušenih z več zaviralci proteaz in naivnih za nenukleozidne zaviralce reverznih transkriptaz.
Sixty-one patients completed the study (35 patients received the recommended 400/ 100 mg twice daily dose throughout the study).
Med 24. in 48. tednom so bolniki, randomizirani na odmerek 400/ 100 mg, prešli na odmerek 533/ 133 mg.
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.
Mediano izhodiščno število celic CD4 je bilo 220 celic/ mm3 (razpon od 13 do 1030 celic/ mm3).
Thirty-nine patients (39%) discontinued the study, including 16 (16%) discontinuations due to adverse events, one of which was associated with a death.
Po analizi z- namenom - zdravljenja obeh odmernih skupin skupaj (n = 57), pri kateri so bili bolniki z manjkajočimi podatki obravnavani kot virološki neuspeh, sta bila delež bolnikov s HIV RNA < 400 (< 50) izvodov/ ml po 48 tednih 65% in povprečno zvečanje števila celic CD4 od izhodišča 94 celic/ mm3.
Patients with prior antiretroviral therapy
Pediatrična uporaba
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.
M98- 940 je odprta študija tekočega pripravka zdravila Kaletra pri 100 protiretrovirusno naivnih (44%) in izkušenih (56%) pediatričnih bolnikih.
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).
Vsi bolniki so bili naivni za nenukleozidne zaviralce reverzne transkriptaze.
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.
Naivni bolniki so dobili tudi nukleozidne zaviralce reverzne transkriptaze.
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.
Varnost, učinkovitost in farmakokinetične profile obeh odmernih shem so pri vsakem bolniku ocenili po 3 tednih zdravljenja.
Between week 24 and 48, patients randomised to a dose of 400/ 100 mg were converted to a dose of 533/ 133 mg.
Potem so vsi bolniki nadaljevali z odmerkom 300/ 75 mg na m2.
Median baseline CD4 cell count was 220 cells/ mm3 (range 13 to 1030 cells/ mm3).
Povprečna starost bolnikov je bila 5 let (razpon: od 6 mesecev do 12 let); 14 bolnikov je bilo mlajših od 2 let in 6 jih je bilo starih eno leto ali manj.
By intent-to-treat analysis of both dose groups combined (n=57), where patients with missing values are considered virologic failures, the proportion of patients
Povprečno izhodiščno število celic CD4 je bilo 838 celic/ mm3, povprečna izhodiščna HIV- 1 RNA v plazmi pa 4, 7 log10 izvodov/ ml.
59 with HIV RNA < 400 copies/ ml at 48 weeks was 65% and the mean increase from baseline CD4 cell count was 94 cells/ mm3.
Med 48 tedni zdravljenja je bil delež bolnikov s HIV RNA < 400 izvodov/ ml 84% med protiretrovirusno naivnimi bolniki in 75% med protiretrovirusno izkušenimi bolniki; povprečno zvečanje števila celic CD4 od izhodišča je bilo 404 celice/ mm3 med prvimi in 284 celic/ mm3 med drugimi.
Paediatric Use
5. 2 Farmakokinetične lastnosti
M98-940 is an open-label study of a liquid formulation of Kaletra in 100 antiretroviral naïve (44%) and experienced (56%) paediatric patients.
Lopinavir se v bistvu popolnoma presnovi s CYP3A.
All patients were non-nucleoside reverse transcriptase inhibitor naïve.
Ritonavir zavira presnovo lopinavirja in tako zvečuje koncentracijo lopinavirja v plazmi.
Patients were randomised to either 230 mg lopinavir/ 57.5 mg ritonavir per m2 or 300 mg lopinavir/ 75 mg ritonavir per m2.
Koncentracija ritonavirja v plazmi je bila manj kot 7% tiste, ki je dosežena po odmerjanju ritonavirja 600 mg dvakrat na dan.
Naïve patients also received nucleoside reverse transcriptase inhibitors.
Protivirusna EC50 lopinavirja in vitro je približno 10- krat manjša kot ritonavirja.
Experienced patients received nevirapine plus up to two nucleoside reverse transcriptase inhibitors.
Protivirusno delovanje zdravila Kaletra je torej posledica lopinavirja.
Safety, efficacy and pharmacokinetic profiles of the two dose regimens were assessed after 3 weeks of therapy in each patient.
Večkratno odmerjanje 400/ 100 mg zdravila Kaletra dvakrat na dan 3 do 4 tedne in brez omejevanja obrokov je povzročilo povprečno največjo plazemsko koncentracijo (Cmax) ± SD lopinavirja 9, 6 ± 4, 4 μg/ ml, in sicer približno 4 ure po uporabi.
Subsequently, all patients were continued on the 300/ 75 mg per m2 dose.
Povprečna najmanjša koncentracija v stanju dinamičnega ravnovesja pred jutranjim odmerkom je bila 5, 5 ± 4, 0 μg/ ml.
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.
AUC lopinavirja med 12- urnim odmernim intervalom je bila v povprečju 82, 8 ± 44, 5 μg• h/ ml.
Mean baseline CD4 cell count was 838 cells/ mm3 and mean baseline plasma HIV-1 RNA was 4.7 log10 copies/ ml.
Absolutna biološka uporabnost lopinavirja, koformuliranega z ritonavirjem, pri ljudeh ni ugotovljena.
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.
Uporabe posamičnega odmerka 400/ 100 mg tablet Kaletra na poln želodec (z mastnim obrokom, 872 kcal, 56% iz maščob) v primerjavi z uporabo na tešče ni
5.2 Pharmacokinetic properties
62 spremljala pomembna sprememba Cmax in AUCinf.
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.
Lopinavir se veže na alfa- 1- kisli glikoprotein (AKG) in na albumin, vendar ima večjo afiniteto za AKG.
Lopinavir is essentially completely metabolised by CYP3A.
Lopinavir se izdatno presnavlja s sistemom jetrnega citokroma P450, skoraj izključno z izoencimom CYP3A.
Ritonavir inhibits the metabolism of lopinavir, thereby increasing the plasma levels of lopinavir.
Ritonavir je močan zaviralec CYP3A, zavira presnovo lopinavirja in tako zvečuje koncentracijo lopinavirja v plazmi.