natgillin/translations-raw huggingface dataset:
53 og 64%) histologisk forbedring ved uge 48 sammenlignet med baseline end i placebogrupperne (25 og 33%).
In two placebo-controlled studies (total n=522) in HBeAg positive or in HBeAg negative chronic hepatitis B patients with compensated liver disease, significantly more patients (p < 0.001) in the 10 mg adefovir dipivoxil groups (53 and 64%, 8 respectively) had histological improvement from baseline at week 48 than in the placebo groups (25 and 33%).
Forbedring blev defineret som en reduktion fra baseline på mindst to eller flere points i Knodell’ s nekro- inflammatoriske score uden nogen samtidig forværring i Knodell’ s fibrosescore.
Improvement was defined as a reduction from baseline of two points or more in the Knodell necro-inflammatory score with no concurrent worsening in the Knodell fibrosis score.
Histologisk forbedring blev set, uanset baseline demografiske og hepatitis B karakteristika, herunder tidligere interferon- alfa terapi.
Histological improvement was seen regardless of baseline demographic and hepatitis B characteristics, including prior interferon-alpha therapy.
Høje baseline- ALAT- niveauer (≥ 2 x ULN) og Knodell Histology Activity Index (HAI) score (≥ 10) og lav HBV- DNA (< 7, 6 log10 kopier/ ml) blev forbundet med større histologisk forbedring.
High baseline ALT levels (≥ 2 x ULN) and Knodell Histology Activity Index (HAI) scores (≥ 10) and low HBV DNA (< 7.6 log10 copies/ ml) were associated with greater histological improvement.
Blinde, rangordnede vurderinger af både nekro- inflammatorisk aktivitet og fibrose ved baseline og ved uge 48 påviste, at patienter behandlet med 10 mg adefovirdipivoxil havde bedre nekro- inflammatoriske og fibrosescorer end placebokontrollerede patienter.
Blinded, ranked assessments of both necro- inflammatory activity and fibrosis at baseline and week 48, demonstrated that patients treated with 10 mg adefovir dipivoxil had improved necro-inflammatory and fibrosis scores relative to placebo- treated patients.
Vurdering af forandringen i fibrose efter 48 ugers behandling ved hjælp af Knodell’ s score bekræfter, at patienter behandlet med adefovirdipivoxil 10 mg har større regression og mindre progression af fibrose end patienter i placebobehandling.
Assessment of the change in fibrosis after 48 weeks treatment using the Knodell scores confirms that patients treated with adefovir dipivoxil 10 mg had more regression and less progression of fibrosis than patients treated with placebo.
3, 52 og 3, 91 log10 kopier/ ml sammenlignet med 0, 55 og 1, 35 log10 kopier/ ml), en større procentdel af patienter med ALAT- normalisering (48 og 72% sammenlignet med 16 og 29%) eller en større procentdel af patienter med serum- HBV- DNA under kvantificeringsgrænserne (< 400 kopier/ ml Roche Amplicor Monitor PCR analysen) (21 og 51% sammenlignet med 0%) i sammenligning med placebo.
In the two studies mentioned above, treatment with 10 mg adefovir dipivoxil was associated with significant reductions in serum HBV DNA (3.52 and 3.91 log10 copies/ ml, respectively, versus 0.55 and 1.35 log10 copies/ ml), increased proportion of patients with normalisation of ALT (48 and 72% versus 16 and 29%) or increased proportion of patients with serum HBV DNA below the limits of quantification (< 400 copies/ ml Roche Amplicor Monitor PCR assay) (21 and 51% versus 0%) when compared with placebo.
6% og 11%), efter 48 ugers behandling.
In the study in HBeAg positive patients, HBeAg seroconversion (12%) and HBeAg loss (24%) was observed significantly more frequently in patients receiving 10 mg adefovir dipivoxil than in patients receiving placebo (6% and 11%, respectively) after 48 weeks of treatment.
I undersøgelsen med HBeAg- positive patienter resulterede behandling i mere end 48 uger i yderligere reduktioner af serum- HBV- DNA- niveauerne samt i en øget andel af patienter med ALAT - normalisering, HBeAg- tab og serokonversion.
In the HBeAg positive study, treatment beyond 48 weeks resulted in further reductions in serum HBV DNA levels and increases in the proportion of patients with ALT normalisation, HBeAg loss and seroconversion.
I undersøgelsen med HBeAg- negative patienter, der blev behandlet med adefovirdipivoxil (0- 48 uger), blev der foretaget en blindet re- randomisering med henblik på fortsat behandling med adefovirdipivoxil eller placebo i yderligere 48 uger.
In the HBeAg negative study patients on adefovir dipivoxil (0-48 weeks) were re-randomised in a blinded-manner to continue on adefovir dipivoxil or receive placebo for an additional 48 weeks.
Ved uge 96 blev der hos de patienter, som havde modtaget fortsat behandling med adefovirdipivoxil 10 mg, set en vedvarende hæmning af serum- HBV med bevarelse af den reduktion, der blev observeret ved uge 48.
At week 96, patients continuing on adefovir dipivoxil 10 mg had sustained suppression of serum HBV with maintenance of the reduction seen at week 48.
Hos mere end to tredjedele af patienterne var hæmningen af serum- HBV- DNA forbundet med ALAT- normalisering.
In over two thirds of patients suppression of serum HBV DNA was associated with normalisation of ALT levels.
Hos de fleste patienter, som ikke længere modtog behandling med adefovirdipivoxil, gik serum- HBV- DNA - og ALAT- niveauerne tilbage mod baseline.
In most patients who stopped treatment with adefovir dipivoxil, serum HBV DNA and ALT levels returned towards baseline.
Behandling i 96 uger med adefovirdipivoxil resulterede i en forbedring af leverfibrosen sammenlignet med baseline ved analyser baseret på Ishak’ s score (median forandring:
Treatment with adefovir dipivoxil resulted in improvement in the liver fibrosis from baseline to 96 weeks therapy when analysed using the Ishak score (median change:
Ved benyttelse af Knodell’ s fibrosescore blev der ikke set nogen forskel mellem grupperne med hensyn til median fibrosescore.
No differences in the median fibrosis score were seen between groups using the Knodell fibrosis score.
De patienter, som fuldførte de første 96 uger af undersøgelsen med HBeAg- negative patienter, og som fik behandling med adefovirdipivoxil i løbet af ugerne 49 til 96, blev tilbudt muligheden for at få åben behandling med adefovirdipivoxil fra undersøgelsesuge 97 til og med uge 240.
Patients who completed the first 96 weeks of the HBeAg negative study and received adefovir dipivoxil treatment during weeks 49 to 96, were offered the opportunity to receive open-label treatment with adefovir dipivoxil from study week 97 through to week 240.
Fra starten af behandlingen med
Serum HBV DNA levels remained undetectable and ALT levels normalised in approximately two thirds of patients following treatment with adefovir dipivoxil for up to 240 weeks.
9 adefovirdipivoxil til slutningen af undersøgelsen (uge 240) viste ændringerne af Ishak scores (median forandring:
Clinically and statistically significant improvement in fibrosis was seen in the changes in Ishak scores from the start of adefovir dipivoxil treatment to the end of the study (week 240) (median change:
Δ= - 1) en klinisk og statistisk signifikant forbedring af fibrose.
Δ = -1).
Ved afslutningen af undersøgelsen havde 7 ud af 12 patienter (58%) med brofibrose eller cirrose ved baseline en forbedret Ishak fibrosescore på ≥ 2 point.
By the end of the study, 7 of 12 patients (58%) with bridging fibrosis or cirrhosis at baseline, had an improved Ishak fibrosis score of ≥ 2 points.
Fem af patienterne opnåede og opretholdt HBsAg- serokonversion (HBsAg negativ/ HBsAb positiv).
Five patients achieved and maintained HBsAg seroconversion (HBsAg negative/ HBsAb positive).
Erfaring med præ - og post- levertransplanterede patienter med lamivudin- resistent HBV:
Experience in patients pre- and post-liver transplantation with lamivudine-resistant HBV:
4, 1 og 4, 2 log10 kopier/ ml ved uge 48.
In a clinical study in 394 chronic hepatitis B patients with lamivudine-resistant HBV (pre-liver transplantation (n=186) and post-liver transplantation (n=208)), treatment with 10 mg adefovir dipivoxil resulted in a median reduction in serum HBV DNA of 4.1 and 4.2 log10 copies/ ml, respectively, at week 48.
77 af 109 (71%) patienter og 64 af 159 (40%) patienter HBV- DNA- niveauer, som ikke kunne påvises, ved uge 48 (< 1. 000 kopier/ ml Roche Amplicor Monitor PCR analysen).
In the pre-liver transplantation and post-liver transplantation cohorts 77 of 109 (71%) patients and 64 of 159 (40%) patients, respectively, achieved undetectable HBV DNA levels at week 48 (< 1,000 copies/ ml Roche Amplicor Monitor PCR assay).
Behandling med 10 mg adefovirdipivoxil viste lignende effekt, uanset hvilke mønstre af lamivudin- resistent HBV- DNA- polymerase- mutationer der fandtes ved baseline.
Treatment with 10 mg adefovir dipivoxil showed similar
Forbedringer eller stabilisering blev set i Child- Pugh- Turcotte’ s score.
Improvements or stabilisation were seen in Child-Pugh-Turcotte score.
Normalisering af ALAT, albumin, bilirubin og protrombintid blev set ved uge 48 hos 51- 85% af patienterne.
Normalisation of ALT, albumin, bilirubin and prothrombin time was seen at week 48 in 51-85% of the patients.
I den præ- levertransplanterede kohorte opnåede 25 af 33 (76%) patienter HBV- DNA- niveauer, som ikke kunne påvises, og 84% af patienterne havde ALAT- normalisering ved uge 96.
In the pre-liver transplantation cohort, 25 of 33 (76%) patients achieved undetectable HBV DNA levels and 84% of patients had ALT normalisation at 96 weeks.
I den post - levertransplanterede kohorte opnåede 61 af 94 (65%) og 35 af 45 (78%) af patienterne HBV- DNA - niveauer, som ikke kunne påvises, ved hhv. uge 96 og 144, og 70% og 58% af patienterne udviste ALAT- normalisering ved disse besøg.
In the post-liver transplantation cohort, 61 of 94 (65%) and 35 of 45 (78%) of patients achieved undetectable HBV DNA levels at 96 and 144 weeks, respectively, and 70% and 58% of patients had ALT normalisation at these study visits.
Erfaring med patienter med kompenseret leversygdom og lamivudin- resistent HBV:
Experience in patients with compensated liver disease and lamivudine-resistant HBV:
I en dobbeltblind, sammenlignende undersøgelse af kroniske hepatitis B patienter med lamivudin- resistent HBV (n=58) var der ingen median reduktion i HBV- DNA fra baseline efter 48 ugers behandling med lamivudin.
In a double-blind comparative study in chronic hepatitis B patients with lamivudine-resistant HBV (n=58), there was no median reduction in HBV DNA from baseline after 48 weeks of treatment with lamivudine.
4, 04 log10 kopier/ ml og 3, 59 log10 kopier/ ml).
Forty-eight weeks of treatment with adefovir dipivoxil 10 mg alone or in combination with lamivudine resulted in a similar significant decrease in median serum HBV DNA levels from baseline (4.04 log10 copies/ ml and 3.59 log10 copies/ ml, respectively).
Den kliniske signifikans af disse observerede forandringer i HBV- DNA er ikke fastlagt.
The clinical significance of these observed changes in HBV DNA has not been established.
Erfaring med patienter med dekompenseret leversygdom og lamivudin- resistent HBV:
Experience in patients with decompensated liver disease and lamivudine-resistant HBV:
I 40 HBeAg - positive eller HBeAg- negative patienter med lamivudin- resistent HBV og dekompenseret leversygdom, som blev behandlet med 100 mg lamivudin, resulterede tilføjelsen af behandling med 10 mg adefovirdipivoxil i 52 uger i en median reduktion i HBV- DNA på 4, 6 log10 kopier/ ml.
In 40 HBeAg positive or HBeAg negative patients with lamivudine-resistant HBV and decompensated liver disease receiving treatment with 100 mg lamivudine, addition of 10 mg adefovir dipivoxil treatment for 52 weeks resulted in a median reduction in HBV DNA of 4.6 log10 copies/ ml.
Erfaring med patienter med samtidig HIV- infektion og lamivudin- resistent HBV:
Experience in patients with HIV co-infection and lamivudine-resistant HBV:
I en åben investigatorundersøgelse, hvor der deltog 35 kroniske hepatitis B patienter med lamivudin- resistent HBV, der samtidig var inficerede med HIV, resulterede fortsat behandling med 10 mg adefovirdipivoxil i progressive reduktioner i serum- HBV- DNA- niveauer og ALAT- niveauer igennem hele behandlingsforløbet på op til 144 uger.
In an open-label investigator study in 35 chronic hepatitis B patients with lamivudine-resistant HBV and co-infected with HIV, continued treatment with 10 mg adefovir dipivoxil resulted in progressive reductions in serum HBV DNA levels and ALT levels throughout the course of treatment up to 144 weeks.
I en anden åben, enkeltarmet undersøgelse blev der tilføjet 10 mg adefovirdipivoxil og pegyleret interferon alfa- 2a til den igangværende lamivudin- behandling af 18 patienter, som havde både HIV - og lamivudin- resistent HBV- infektion.
In a second open-label, one-arm study, 10 mg adefovir dipivoxil and pegylated interferon alpha-2a were added to ongoing lamivudine therapy in 18 HIV/ HBV co-infected patients with lamivudine-resistant HBV.
Patienterne var alle testet positive for HBeAg og havde et mediant CD4- celletal på 441 celler/ mm3 (ingen patienter havde CD4- celletal < 200 celler/ mm3).
Patients were all HBeAg positive and had median CD4 cell count of 441 cells/ mm3 (no patient had CD4 count < 200 cells/ mm3).
Under behandlingen var serum- HBV- DNA- niveauerne betydeligt lavere end ved baseline i op til 48 uger af behandlingen, mens ALAT- niveauerne faldt progressivt fra uge 12.
During therapy, serum HBV DNA levels were significantly lower compared to baseline for up to 48 weeks of treatment while ALT levels declined progressively from week 12.
Imidlertid blev HBV- DNA - responset ikke opretholdt efter behandlingen, da der hos alle patienter var en forværring af HBV- DNA efter seponering af adefovirdipivoxil og pegyleret interferon- alfa- 2a.
However, on-treatment HBV DNA response was not maintained off-therapy since all the patients had a rebound in HBV DNA after adefovir dipivoxil and pegylated interferon alpha-2a discontinuation.
Ingen patienter blev HBsAg - eller HBeAg- negative i løbet af undersøgelsen.
No patients became HBsAg- or HBeAg-negative during the study.
På grund af den ringe populationsstørrelse og undersøgelsens opbygning, især udeladelsen af behandlingsarme med pegyleret interferon alfa- 2a - monobehandling og adefovir- monobehandling, er det ikke muligt at udlede formelle konklusioner om en optimal behandlingsstrategi hos disse patienter, der har både HIV - og lamivudin- resistent HBV- infektion.
Due to the small sample size and the study design, in particular the lack of treatment arms with pegylated interferon alpha-2a monotherapy and with adefovir monotherapy, it is not possible to draw formal conclusions on the best therapeutic management of HIV co-infected patients with lamivudine-resistant HBV.
10 Pædiatrisk population:
Paediatric population:
Virkningen og sikkerheden af en daglig dosis fra 0, 25 mg/ kg op til 10 mg adefovirdipivoxil hos børn (i alderen 2 til < 18 år) blev undersøgt i en dobbeltblind, randomiseret, placebo- kontrolleret klinisk undersøgelse med 173 pædiatriske patienter (115 fik adefovirdipivoxil, 58 fik placebo), som havde HBeAg- positiv kronisk hepatitis B, serum- ALAT- niveauer ≥ 1, 5 x øvre grænse af normal (ULN) og kompenseret leversygdom.
The efficacy and safety of a daily dose of 0.25 mg/ kg to 10 mg adefovir dipivoxil in children (aged from 2 to < 18 years) was examined in a double-blind, randomised, placebo-controlled study in 173 paediatric patients (115 on adefovir dipivoxil, 58 on placebo) who had HBeAg positive chronic hepatitis B, serum ALT levels ≥ 1.5 x upper limit of normal (ULN) and compensated liver disease.
Ved uge 48 blev der ikke observeret nogen statistisk signifikant forskel mellem placebo- armen og adefovirdipivoxil- armen hos børn i alderen 2 til 11 år blandt de patienter, som opnåede det primære endpoint, som var serum- HBV- DNA < 1. 000 kopier/ ml og normale ALAT- niveauer.
At week 48, in children aged 2 to 11 years old, no statistically significant difference was observed in the proportions of patients that achieved the primary endpoint of serum HBV DNA < 1,000 copies/ ml and normal ALT levels between the placebo arm and the adefovir dipivoxil arm.
Signifikant flere af de unge patienter (n=83) (i alderen 12 til < 18 år), der blev behandlet med adefovirdipivoxil, opnåede det primære virknings- endpoint og havde væsentlige fald i serum- HBV- DNA (23%) sammenlignet med de placebo- behandlede unge patienter (0%).
In the adolescent population (n=83) (aged from 12 to < 18 years), significantly more patients treated with adefovir dipivoxil achieved the primary efficacy endpoint and obtained significant reductions in serum HBV DNA (23%) compared to placebo-treated patients (0%).
Andelen af de unge patienter, som opnåede HBeAg- serokonversion (11%) ved uge 48 var imidlertid nogenlunde ens i både placebo- armen og adefovirdipivoxil- armen med 10 mg.
However, the proportions of subjects who achieved HBeAg seroconversion at week 48 were similar (11%) between the placebo arm and the adefovir dipivoxil 10 mg arm in adolescent patients.
Sikkerhedsprofilen for adefovirdipivoxil hos børn var generelt den samme som den kendte sikkerhedsprofil for voksne patienter.
10 Overall, the safety profile of adefovir dipivoxil in children was consistent with the known safety profile in adult patients.
Der synes dog at være tegn på, at der i adefovir- armen var en større andel patienter, der havde nedsat appetit og/ eller spiste mindre end i placebo- armen.
However, a signal towards a higher rate of decreased appetite and/ or food intake was observed in the adefovir arm as compared to the placebo arm.
Ved uge 48 og 96 var der tendens til, at middelændringer fra baseline i vægt - og BMI Z- scorer steg hos patienter, som blev behandlet med adefovirdipivoxil.
At week 48 and 96, mean changes from baseline in weight and BMI Z scores tended to decrease in adefovir dipivoxil-treated patients.
For børn findes der hverken langtidsdata om sikkerheden af eller resistensen over for adefovirdipivoxil.
No long-term safety data or long-term resistance data are available with adefovir dipivoxil in children.
4. 2).
The clinical data available are insufficient to draw definitive conclusions on the benefit/ risk ratio of the adefovir treatment in children with chronic hepatitis B (see section 4.2).
Klinisk resistens hos patienter, der fik adefovirdipivoxil som monoterapi og i kombination med lamivudin:
Clinical resistance in patients receiving adefovir dipivoxil as monotherapy and in combination with lamivudine:
I flere kliniske undersøgelser (HBeAg- positive, HBeAg- negative, præ - og post - levertransplanterede patienter med lamivudin- resistent HBV og patienter med lamivudin- resistent HBV, der samtidig var inficeret med HIV) blev genotypeanalyser udført på HBV- isolater fra 379 ud af i alt 629 patienter, som var blevet behandlet med adefovirdipivoxil i 48 uger.
In several clinical studies (HBeAg positive, HBeAg negative, pre- and post-liver transplantation with lamivudine-resistant HBV and lamivudine-resistant HBV co-infected with HIV patients), genotypic analyses were conducted on HBV isolates from 379 of a total of 629 patients, treated with adefovir dipivoxil for 48 weeks.
Ingen HBV- DNA - polymerase- mutationer forbundet med resistens over for adefovir blev identificeret, da patienter blev genotypeanalyseret ved baseline og uge 48.
No HBV DNA polymerase mutations associated with resistance to adefovir were identified when patients were genotyped at baseline and at week 48.
To hidtil ukendte bindingstedsmutationer i et konserveret område blev identificeret i HBV- polymerasegenet (rtN236T og rtA181V) og medførte klinisk adefovirdipivoxilresistens.
Two novel conserved site mutations were identified in the HBV polymerase gene (rtN236T and rtA181V), which conferred clinical resistance to adefovir dipivoxil.
De kumulative sandsynligheder for udvikling af disse adefovirforbundne resistensmutationer hos alle patienter i behandling med adefovirdipivoxil var 0% ved 48 uger og cirka 2%, 7%, 14% og 25% efter henholdsvis 96, 144, 192 og 240 uger.
The cumulative probabilities of developing these adefovir-associated resistance mutations in all patients treated with adefovir dipivoxil were 0% at 48 weeks and approximately 2%, 7%, 14% and 25% after 96, 144, 192 and 240 weeks, respectively.
Klinisk resistens ved monoterapiundersøgelser hos nucleosid- naive patienter:
Clinical resistance in monotherapy studies in nucleoside naïve patients:
48, 96, 144, 192 og 240 uger.
In patients receiving adefovir dipivoxil monotherapy (HBeAg negative study) the cumulative probability of developing adefovir-associated resistance mutations was 0%, 3%, 11%, 18% and 29% at 48, 96, 144, 192 and 240 weeks respectively.
Derudover var den langsigtede (4 til 5 år) udvikling af resistens over for adefovirdipivoxil signifikant lavere hos patienter, der havde serum- HBV- DNA under grænsen for kvantificering (< 1. 000 kopier/ ml ved uge 48) sammenlignet med patienter, der havde serum - HBV- DNA på over 1. 000 kopier/ ml ved uge 48.
In addition, the long-term (4 to 5 years) development of resistance to adefovir dipivoxil was significantly lower in patients who had serum HBV DNA below the limit of quantification (< 1,000 copies/ ml) at week 48 as compared to patients with serum HBV DNA above 1,000 copies/ ml at week 48.
135, 189 og 235 uger.
In HBeAg positive patients, the incidence of adefovir-associated resistance mutations was 3% (2/ 65), 17% (11/ 65) and 20% (13/ 65) after a median duration exposure of 135, 189 and 235 weeks respectively.
Klinisk resistens ved undersøgelser, hvor adefovirdipivoxil blev føjet til igangværende lamivudinbehandling hos patienter med lamivudinresistens:
Clinical resistance in studies where adefovir dipivoxil was added to ongoing lamivudine in patients with lamivudine-resistance:
I en åben undersøgelse af præ - og post - levertransplanterede patienter med kliniske tegn på lamuvidinresistent HBV, blev der ikke observeret adefovirforbundne resistensmutationer ved uge 48.
In an open-label study of pre- and post-liver transplantation patients with clinical evidence of lamivudine-resistant HBV, no adefovir-associated resistance mutations were observed at week 48.
Alle 4 patienter fik serum- HBV tilbagefald.
However, 4 patients who discontinued lamivudine treatment developed the rtN236T mutation while receiving adefovir dipivoxil monotherapy and all experienced serum HBV rebound.
11 De nuværende tilgængelige data både in vitro og hos patienter tyder på, at HBV, som eksprimerer den adefovirforbundne resistensmutation rtN236T, er følsom over for lamivudin.
The currently available data both in vitro and in patients suggest that HBV expressing the adefovir- associated resistance mutation rtN236T is susceptible to lamivudine.
Adefovirdipivoxil er et dipivaloyloxymethylester- prodrug af det aktive stof adefovir.
Adefovir dipivoxil is a dipivaloyloxymethyl ester prodrug of the active substance adefovir.
Den perorale biotilgængelighed af adefovir fra 10 mg adefovirdipivoxil er 59%.
The oral bioavailability of adefovir from 10 mg adefovir dipivoxil is 59%.
Efter peroral indgivelse af en enkelt dosis af 10 mg adefovirdipivoxil hos kroniske hepatitis B patienter blev den mediane (område) peak- serumkoncentration (Cmax) opnået efter 1, 75 time (0, 58- 4, 0 time).
Following oral administration of a single dose of 10 mg adefovir dipivoxil to chronic hepatitis B patients, the median (range) peak serum concentration (Cmax) was achieved after 1.75 h (0.58-4.0 h).
16, 70 (9, 66- 30, 56) ng/ ml og 204, 40 (109, 75- 356, 05) ng· t/ ml.
Median Cmax and AUC0-∞ values were 16.70 (9.66-30.56) ng/ ml and 204.40 (109.75-356.05) ng·h/ ml, respectively.
Fordeling:
11 Distribution:
Prækliniske undersøgelser har vist, at adefovir efter peroral indgivelse af adefovirdipivoxil fordeles til de fleste væv, hvor de højeste koncentrationer forekommer i nyre -, lever - og tarmvæv.
Preclinical studies show that after oral administration of adefovir dipivoxil, adefovir is distributed to most tissues with the highest concentrations occurring in kidney, liver and intestinal tissues.