natgillin/translations-raw huggingface dataset:
Limited historical data indicate that treatment for 48 weeks might be associated with a higher sustained response rate (11/11) and with a lower risk of relapse (0/11 as compared to 7/96 following 24 weeks of treatment).
18 Omejena količina predhodnih podatkov kaže, da je lahko zdravljenje, ki traja 48 tednov, povezano z večjo stopnjo stalnega virološkega odziva (11/ 11) in z manjšim tveganjem za relaps (0/ 11 v primerjavi s 7/ 96 po 24 tednih zdravljenja).
Predictability of sustained virological response in naïve patients Virological response by week 12, defined as a 2-log viral load decrease or undetectable levels of HCV RNA has been shown to be predictive for sustained response (Table 8).
Predvidljivost trajnega virološkega odziva pri predhodno nezdravljenih bolnikih Pokazali so, da je virološki odziv do 12. tedna, opredeljen kot 2- log zmanjšanje virusne obremenitve ali nemerljive koncentracije HCV RNK, dober napovednik za trajen odziv (Preglednica 8).
Predictability of sustained response by viral response at week 12 and genotype*
Predvidljivost trajnega virološkega odziva po odzivu v 12. tednu in genotipu *
Treatment
Trajen odziv
Genotype Viral response at Sustained response Negative week 12 predictive value
Negativna napovedna vrednost
Rebetol (> 10.6mg/kg) 1 +peginterferon alfa-2b
(> 10, 6 mg/ kg) + peginterferon alfa
Yes 75% (82/110)
da 75% (82/ 110)
1.5 48-week treatment
- 2b 1, 5 48 - tedensko zdravljenje Rebetol
No 25% (28/110)
ne 25% (28/ 110)
Rebetol 800-1400 mg 2 and 3 +peginterferon alfa-2b
800 – 1. 400 mg + peginterferon alfa - 2b 1, 5 24 - tedensko zdravljenje
Yes 99% (213/215) 83%
da 99% (213/ 215)
No 1% (2/215)
ne 1% (2/ 215)
HCV/HIV Co-infected patients Two trials have been conducted in patients co-infected with HIV and HCV.
Bolniki, sočasno okuženi s HCV in HIV Pri bolnikih, sočasno okuženih z virusoma HIV in HCV, sta bili opravljeni dve preskušanji.
The response to treatment in both of these trials is presented in Table 9.
V Preglednici 9 je predstavljen odziv bolnikov na zdravljenje pri obeh preskušanjih.
Study 1 (RIBAVIC; P01017) was a randomized, multicentre study which enrolled 41 2 previously untreated adult patients with chronic hepatitis C who were co-infected with HIV.
Študija 1 (RIBAVIC; P01017) je bila randomizirana, multicentrična študija, v katero so vključili 412 predhodno nezdravljenih odraslih bolnikov s kroničnim hepatitisom C, ki so bili sočasno okuženi tudi z virusom HIV.
Patients were randomized to receive either Rebetol (800 mg/day) plus peginterferon alfa-2b (1.5 µg/kg/week) or Rebetol (800 mg/day) plus interferon alfa-2b (3 MIU TIW) for 48 weeks with a follow-up period of 6 months.
Bolnike so naključno razporedili bodisi v skupino, ki bo prejemala zdravili Rebetol (800 mg/ dan) in peginterferon alfa- 2b (1, 5 µg/ kg/ teden), ali pa v skupino, ki bo prejemala zdravili Rebetol (800 mg/ dan) in interferon alfa- 2b (3 milijone i. e. trikrat na teden) v času 48 tednov, s 6 - mesečnim spremljanjem.
Patients were randomized to receive either Rebetol (800-1,200 mg/day based on weight) plus peginterferon alfa-2b (100 or 150 µg/week based on weight) or Rebetol (800- 1,200 mg/day based on weight) plus interferon alfa-2b (3 MIU TIW).
Bolnike so naključno razporedili bodisi v skupino, ki bo prejemala zdravili Rebetol (800- 1. 200 mg/ dan glede na telesno maso) in peginterferon alfa- 2b (100 ali 150 µg/ teden glede na telesno maso) ali pa zdravili Rebetol (800- 1. 200 mg/ dan glede na telesno maso) in interferon alfa- 2b (3 milijone i. e. trikrat na teden).
The duration of therapy was 18 48 weeks with a follow-up period of 6 months except for patients infected with genotypes 2 or 3 and viral load < 800,000 IU/ml (Amplicor) who were treated for 24 weeks with a 6 month follow-up period.
Zdravljenje je trajalo 48 tednov, bolnike pa so spremljali 6 mesecev, razen tistih, ki so bili okuženi z genotipoma 2 ali 3 in so imeli virusno breme < 800. 000 i. e. / ml (Amplicor) - te so zdravili 24 tednov in jih spremljali 6 mesecev.
Table 9 Sustained virological response based on genotype after Rebetol in combination with peginterferon alfa-2b in HCV/HIV co-infected patients
Stalni virološki odziv glede na genotip po jemanju zdravila Rebetol v kombinaciji s peginterferonom alfa- 2b pri bolnikih, sočasno okuženih s HCV in HIV
Rebetol (800- Rebetol (800-
Rebetol (800 - Rebetol (800 - 1200 mg/ dand 1200 mg/ dand
(800 mg/day)
(800 mg/ dan) (800 mg/ dan) +
peginterferon (800 mg/day) + peginterferon
Interferon alfa - +
alfa-2b
Vredno
Interferon alfa-
peginterferon
alfa-2b (100
2b (3 milijone Vredn peginterferon ost pa
Interferon
Interferon
(1.5 µg /kg/
st pb
p
i. e. trikrat na alfa- 2b (100
or 150c
alfa- 2b
alfa-2 b
19
p
(1, 5 µg/ kg /
b
teden)
week)
ali
TIW)
(3 milijone
value a
150cµg/ teden)
µg/week)
teden)
(3 MIU TIW) value
i. e. trikrat na teden)
All Genotype 1, 17 4
Vsi Genotip 1, 4
27% (56/205) 20%% (21/125)
20% (41/ 205) 6% (8/ 129)
(41/205) 0.047 6% (8/129)
0, 047 0, 006
Genotype 2, 44% (35/80) 3
Genotip 2, 3
Rebetol dosing was 800 mg for patients < 60 kg, 1,000 mg for patients 60-75 kg, and 1,200 mg for patients > 75 kg.
Mio i. e. = milijonov mednarodnih enot a: vrednost p pri Cochran- Mantel Haenszelovem testu hi- kvadrat b: vrednost p pri testu hi- kvadrat c: preiskovanci s telesno maso < 75 kg so prejemali 100 µg peginterferona alfa- 2b na teden, preiskovanci s telesno maso ≥ 75 kg pa so prejemali 150 µg peginterferona alfa- 2b na teden. d: odmerek Rebetola je znašal 800 mg za bolnike s telesno maso < 60 kg, 1000 mg za bolnike s telesno maso od 60 do 75 kg in 1200 mg za tiste s telesno maso > 75 kg.
Histological response Liver biopsies were obtained before and after treatment in Study 1 and were available for 210 of the 412 subjects (51%).
Histološki odziv na zdravljenje V študiji 1 so biopsijo jeter opravili pred in po zdravljenju - na voljo so podatki za 210 od 412 preiskovancev (51%).
Both the Metavir score and Ishak grade decreased among subjects treated with Rebetol in combination with peginterferon alfa-2b.
Pri preiskovancih, zdravljenih z zdravilom Rebetol v kombinaciji s peginterferonom alfa- 2b, sta se zmanjšali tako ocena po Metavirju kot ocena po Ishaku.
This decline was significant among responders (-0.3 for Metavir and -1.2 for Ishak) and stable (-0.1 for Metavir and -0.2 for Ishak) among non- responders.
Ta upad je bil statistično značilen pri bolnikih, ki so se odzvali na zdravljenje (- 0, 3 pri oceni po Metavirju in - 1, 2 pri oceni po Ishaku) in stabilen (- 0, 1 pri oceni po Metavirju in - 0, 2 pri oceni po Ishaku) pri tistih, ki se niso odzvali na zdravljenje.
There was no improvement in terms of fibrosis observed in this study.
Kar zadeva aktivnost bolezni, se je pri približno eni tretjini bolnikov s stalnim odzivom pokazalo izboljšanje, pri nobenem od bolnikov pa ni prišlo do poslabšanja.
Previous treatment failure patients Retreatment of prior treatment failures (relapse and non-responder patients) with peginterferon alfa- 2b in combination with Rebetol In a non-comparative trial, 2,293 patients with moderate to severe fibrosis who failed previous treatment with combination alpha interferon/ribavirin were retreated with peginterferon alfa 2b, 1.5 microgram/kg subcutaneously, once weekly, in combination with weight adjusted Rebetol.
Bolniki, pri katerih je bilo prejšnje zdravljenje neuspešno Ponovno zdravljenje s peginterferonom alfa- 2b v kombinaciji z zdravilom Rebetol v primeru neuspešnega prejšnjega zdravljenja (za bolnike s ponovitvijo bolezni in tiste, ki se niso odzvali na predhodno terapijo) V neprimerjalnem preskušanju so skupaj 2293 bolnikov z zmerno do hudo fibrozo, pri katerih je bilo predhodno zdravljenje s kombinacijo interferona alfa in ribavirina neuspešno, ponovno zdravili s peginterferonom alfa- 2b v odmerku 1, 5 mikrograma/ kg enkrat na teden subkutano, v kombinaciji z zdravilom Rebetol v odmerku, odvisnem od bolnikove telesne mase.
Failure to prior therapy was defined as relapse or non-response (HCV-RNA positive at the end of a minimum of 12 weeks of treatment).
Neuspešnost prejšnjega zdravljenja so opredelili kot ponovitev bolezni (relaps) ali odsotnost odziva na zdravljenje (bolniki so imeli pozitiven izvid na HCV- RNA ob koncu najmanj 12- tedenskega zdravljenja).
Patients who were HCV-RNA negative at Treatment Week 12 continued treatment for 48 weeks and were followed for 24 weeks post-treatment.
Bolniki, ki so imeli negativen izvid na HCV- RNA v 12. tednu zdravljenja, pa so nadaljevali z zdravljenjem še 48 tednov, po zdravljenju pa so jih spremljali še 24 tednov.
Response Week 12 was defined as undetectable HCV- RNA after 12 weeks of treatment.
Odziv v 12. tednu so opredelili kot nezaznavno količino HCV- RNA po 12. tednih zdravljenja.
Sustained Virologic Response (SVR) is defined as undetectable HCV-RNA at 24 weeks post-treatment (Table 10).
Stalen virološki odziv (SVR) pa je bil opredeljen kot nezaznavna vrednost HCV- RNA 24 tednov po zdravljenju (Preglednica 10).
Table 10 Rates of Response to retreatment in prior treatment failures
Stopnje odziva na ponovno zdravljenje v primeru, da je bilo prejšnje zdravljenje neuspešno
Patients with undetectable HCV–RNA 19 at treatment Week 12 and SVR upon retreatement Overall
Bolniki, pri katerih je bila vrednost HCV– RNA nemerljiva v 12. tednu zdravljenja in SVR pri ponovnem zdravljenju
interferon alpha/ribavirin
interferon alfa/ ribavirin
peginterferon alpha/ribavirin
peginterferon alfa/ ribavirin
Population*
Skupaj *
Response Week 12% (n/N)
Odziv v 12. tednu% (n/ N)
SVR% (n/ N) 99% CI
SVR% (n/ N) 99% IZ
Response SVR% (n/N) Week 12% 99% CI (n/N)
SVR% (n/ N) tednu% (n/ N) 99% IZ
SVR% (n/N) 99% CI
SVR% (n/ N) 99% IZ
Overall Prior Response
Skupaj Prejšnji odziv
38.6 (549/1,423) 59.4 (326/549) 54.0,64.8
38, 6 (549/ 1423) 59, 4 (326/ 549) 54, 0, 64, 8
31.5 (272/863) 50.4 (137/272) 42.6, 58.2
31, 5 (272/ 863) 50, 4 (137/ 272) 42, 6, 58, 2
21.7 (497/2,293) 19.5, 23.9
21, 7 (497/ 2293) 19, 5, 23, 9
67.7 (203/300)
67, 7 (203/ 300)
59.6 (121/203) 50.7, 68.5
59, 6 (121/ 203) 50, 7, 68, 5
52.5 (105/200) 43.4, 61.6
52, 5 (105/ 200) 43, 4, 61, 6
51.2 (66/129) 39.8, 62.5
51, 2 (66/ 129) 39, 8, 62, 5
44.3 (54/122) 32.7, 55.8
44, 3 (54/ 122) 32, 7, 55, 8
28.6 (134/468) 23.3, 34.0
28, 6 (134/ 468) 23, 3, 34, 0
73.6 (53/72) (60.2, 87.0)
73, 6 (53/ 72) (60, 2, 87, 0)
64.9 (50/77) 50.9, 78.9
64, 9 (50/ 77) 50, 9, 78, 9
61.3 (106/173) 51.7, 70.8
61, 3 (106/ 173) 51, 7, 70, 8
NR
Neodzivni (NR)
57.0 (147/258) 49.0, 64.9
57, 0 (147/ 258) 49, 0, 64, 9
44.1 (26/59) 27.4, 60.7
44, 1 (26/ 59) 27, 4, 60, 7
13.6 (188/1,385) 11.2, 15.9
13, 6 (188/ 1385) 11, 2, 15, 9
38.6 (17/44) 19.7, 57.5
38, 6 (17/ 44) 19, 7, 57, 5
9.9 (123/1,242) 7.7, 12.1
9, 9 (123/ 1242) 7, 7, 12, 1
70.3 (52/74) 56.6, 84.0
70, 3 (52/ 74) 56, 6, 84, 0
60.0 (9/ 15) 27.4, 92.6
60, 0 (9/ 15) 27, 4, 92, 6
46.0 (63/137) 35.0, 57.0
46, 0 (63/ 137) 35, 0, 57, 0
51.3 (176/343) 44.4, 58.3
51, 3 (176/ 343) 44, 4, 58, 3
42.6 (69/162) 32.6, 52.6
42, 6 (69/ 162) 32, 6, 52, 6
14.6 (270/1,846) 12.5, 16.7
14, 6 (270/ 1846) 12, 5, 16, 7
73.0 (135/185) 64.6, 81.4
73, 0 (135/ 185) 64, 6, 81, 4
75.6 (96/127) 63.5 (61/96) 50.9, 76.2
75, 6 (96/ 127) 63, 5 (61/ 96) 50, 9, 76, 2
55.3 (203/367) 48.6, 62.0
55, 3 (203/ 367) 48, 6, 62, 0
70.6 (12/17) 42.1, 99.1
70, 6 (12/ 17) 42, 1, 99, 1
44.4 (12/27) 50.0 (6/12) 12.8, 87.2
44, 4 (12/ 27) 50, 0 (6/ 12) 12, 8, 87, 2
28.4 (19/67) 14.2, 42.5
28, 4 (19/ 67) 14, 2, 42, 5
METAVIR Fibrosis score
METAVIR Ocena fibroze
66.8 (129/193) 58.1, 75.6
66, 8 (129/ 193) 58, 1, 75, 6
57.7 (45/78) 43.3, 72.1
57, 7 (45/ 78) 43, 3, 72, 1
29.2 (191/653) 24.7, 33.8
29, 2 (191/ 653) 24, 7, 33, 8
62.6 (102/163) 52.8, 72.3
62, 6 (102/ 163) 52, 8, 72, 3
51.3 (40/78) 36.7, 65.9
51, 3 (40/ 78) 36, 7, 65, 9
21.9 (147/672) 17.8, 26.0
21, 9 (147/ 672) 17, 8, 26, 0
49.5 (95/192) 40.2, 58.8
49, 5 (95/ 192) 40, 2, 58, 8
44.8 (52/116) 32.9, 56.7
44, 8 (52/ 116) 32, 9, 56, 7
16.5 (159/966) 13.4, 19.5
16, 5 (159/ 966) 13, 4, 19, 5
Baseline Viral Load HVL (> 600,000 IU/ml)
Začetno virusno breme HVL (> 600 000 i. e. / ml)
56.1 (157/280) 48.4, 63.7
56, 1 (157/ 280) 48, 4, 63, 7
41.4 (63/152) 31.2, 51.7
41, 4 (63/ 152) 31, 2, 51, 7
16.6 (239/1,441) 14.1, 19.1
16, 6 (239/ 1441) 14, 1, 19, 1
LVL (≤600,000 IU/ml)
LVL (≤600 000 i. e. / ml)
62.8 (169/269) 55.2, 70.4
62, 8 (169/ 269) 55, 2, 70, 4
61.0 (72/118) 49.5, 72.6
61, 0 (72/ 118) 49, 5, 72, 6
30.2 (256/848) 26.1, 34.2
30, 2 (256/ 848) 26, 1, 34, 2
Non-responder defined as serum/plasma HCV-RNA positive at the end of a minimum of 12 weeks of treatment.
Neodzivni bolniki so opredeljeni kot tisti, ki imajo pozitiven izvid na serumsko ali plazemsko HCV- RNA ob koncu najmanj 12 tednov zdravljenja.
Plasma HCV-RNA is measured with a research-based quantitative polymerase chain reaction assay by a central laboratory * Intent to treat population includes 7 patients for whom at least 12 weeks of prior therapy could not be confirmed.
Plazemska vrednost HCV- RNA je bila izmerjena s raziskovalnim kvantitativnim testom polimerazne verižne reakcije v centralnem laboratoriju. * V skupini, ki so jo nameravali zdraviti, je bilo 7 ljudi, pri katerih ni bilo mogoče potrditi najmanj 12 tednov predhodnega zdravljenja.
Overall, approximately 36% (821/2,286) of patients had undetectable plasma HCV-RNA levels at Week 12 of therapy measured using a research-based test (limit of detection 125 IU/ml).
Skupaj je imelo v 12. tednu zdravljenja približno 36% (821/ 2286) bolnikov nezaznavne koncentracije HCV- RNA v plazmi, kar so merili z raziskovalnim testom (meja detekcije 125 i. e. / ml).
In this subgroup, there was a 56% (463/823) sustained virological response rate.
V tej podskupini je bila stopnja stalnega virološkega odziva 56% (463/ 823).
For patients with prior failure on therapy with nonpegylated interferon or pegylated interferon and negative at Week 12, the sustained response rates were 59% and 50%, respectively.
Pri bolnikih s predhodno neuspešnim zdravljenjem z nepegiliranim interferonom oziroma s pegiliranim interferonom in negativnim izvidom v 12. tednu sta bili pogostnosti stalnega virološkega odziva 59% oziroma 50%.
Among 480 patients with > 2 log viral reduction but detectable virus at Week 12, altogether 188 patients continued therapy.
Med 480 bolniki z zmanjšanjem količine virusa za > 2 log vrednosti, vendar še vedno z merljivo količino virusa v krvi v 12. tednu zdravljenja, je z zdravljenjem nadaljevalo skupaj 188 bolnikov.
In those patients the SVR was 12%.
Pri teh bolnikih je vrednost SVR znašala 12%.
20 Non-responders to prior therapy with pegylated interferon alpha/ribavirin were less likely to achieve a Week 12 response to retreatment than non-responders to nonpegylated interferon alpha/ribavirin (12.4% vs.
Pri bolnikih, ki se niso odzvali na predhodno zdravljenje s pegiliranim interferonom alfa/ ribavirinom, je bila verjetnost, da se bodo odzvali na ponovno zdravljenje v 12. tednu, manjša kot pri tistih, ki se niso odzvali na zdravljenje z nepegiliranim interferonom alfa/ ribavirinom (12, 4% v primerjavi z 28, 6%).
However, if a Week 12 response was achieved, there was little difference in SVR regardless of prior treatment or prior response.
Če pa se je v 12. tednu pojavil odziv na zdravljenje, je bila razlika v stalnem virološkem odzivu (SVR) majhna, ne glede na predhodno zdravljenje ali bolnikov predhodni odziv na zdravljenje.
Retreatment of relapse patients with Rebetol and interferon alfa-2b combination treatment Two trials examined the use of Rebetol and interferon alfa-2b combination treatment in relapse patients (C95-144 and I95-145); 345 chronic hepatitis patients who had relapsed after previous interferon treatment were treated for six months with a six month follow-up.
21 Ponovno zdravljenje bolnikov s ponovitvijo bolezni z zdravilom Rebetol in interferonom alfa- 2b v kombinirani terapiji V dveh preskušanjih so raziskovali uporabo kombinacije zdravil Rebetol + interferona alfa- 2b pri bolnikih s ponovitvijo bolezni (C95- 144 in I95- 145); 345 bolnikov s kroničnim hepatitisom, pri katerih se je bolezen ponovila po predhodnem zdravljenju z interferonom, so zdravili šest mesecev, in jih nato spremljali še šest mesecev.
Combination therapy with Rebetol and interferon alfa-2b resulted in a sustained virological response that was ten-fold higher than that with interferon alfa-2b alone (49% vs 5%, p < 0.0001).
Pri kombinirani terapiji z zdravilom Rebetol + interferonom alfa - 2b je bil trajen virološki odziv kar desetkrat večji kot pri monoterapiji z interferonom alfa- 2b (49% proti 5%, p < 0, 0001).
This benefit was maintained irrespective of standard predictors of response to interferon alfa-2b such as virus level, HCV genotype and histological staging.
Ta koristen učinek se je ohranjal ne glede na standardne napovedne dejavnike odziva na interferon alfa- 2b, npr. virusno breme, HCV genotip in histološka stopnja bolezni.
Long-term efficacy data Two large long-term follow-up studies enrolled 1,071 patients and 567 patients after treatment in prior studies with nonpegylated interferon alfa-2b (with or without Rebetol) and pegylated interferon alfa- 2b (with or without Rebetol), respectively.
Dolgoročni podatki o učinkovitosti V dve veliki, dolgoročni študiji spremljanja bolnikov po zdravljenju v prejšnjih študijah so vključili skupaj 1071 bolnikov po končanem zdravljenju z nepegiliranim interferonom alfa- 2b (z ali brez Rebetola) ter 567 bolnikov po končanem zdravljenju s pegiliranim interferonom alfa- 2b (z ali brez Rebetola).
At least 5 years of long-term follow-up was completed after treatment in 462 patients and 327 patients, respectively.
Pri 462 bolnikih oziroma pri 327 bolnikih je bilo opravljeno najmanj 5- letno dolgoročno spremljanje.
12 out of 492 sustained responders and only 3 out of 366 sustained responders relapsed, respectively, in the studies.
V študijah se je bolezen ponovila pri 12 od 492 bolnikov s trajnim virološkim odzivom iz prve skupine in le pri 3 od 366 bolnikov s trajnim virološkim odzivom iz druge skupine.
The Kaplan-Meier estimate for continued sustained response over 5 years is 97% (95% CI:
Kaplan- Meierjeva ocena nadaljnjega neprekinjenega trajnega odziva v času 5 let je znašala 97% (95% IZ:
95-99%) for patients receiving nonpegylated interferon alfa-2b (with or without Rebetol), and is 99% (95% CI:
95- 99%) pri bolnikih, ki so prejemali nepegiliran interferon alfa- 2b (z ali brez Rebetola), oziroma 99% (95% IZ:
98-100%) for patients receiving pegylated interferon alfa-2b (with or without Rebetol).
98- 100%) pri tistih, ki so prejemali pegiliran interferon alfa- 2b (z ali brez Rebetola).
SVR after treatment of chronic HCV with interferon alfa-2b (pegylated and nonpegylated,with or without Rebetol) results in long-term clearance of the virus providing resolution of the hepatic infection and clinical'cure' from chronic HCV.
Stalni virološki odziv (SVR – » sustained virologic response «) po zdravljenju kronične okužbe z virusom hepatitisa C z interferonom alfa- 2b (pegiliranim ali nepegiliranim, z ali brez zdravila Rebetol) vodi dodolgotrajnega očistka virusa ter tako odpravi jetrno okužbo in omogoči klinično » ozdravitev « kronične okužbe z virusom hepatitisa C.
Rebetol clinical trials in children and adolescents:
Klinična preskušanja zdravila Rebetol pri otrocih in mladostnikih:
Children and adolescents 3 to 16 years of age with compensated chronic hepatitis C and detectable HCV-RNA (assessed by a central laboratory using a research-based RT-PCR assay) were enrolled in two multicentre trials and received Rebetol 15 mg/kg per day plus interferon alfa-2b 3 MIU/m2 3 times a week for 1 year followed by 6 months follow-up after treatment.
Otroci in mladostniki, stari od 3 do 16 let in s kompenziranim kroničnim hepatitisom C in merljivimi količinami HCV RNA (kar je ocenil osrednji laboratorij z uporabo raziskovalnega testa RT- PCR), so bili vključeni v dve multicentrični preskušanji in so zdravilo Rebetol prejemali v odmerku 15 mg/ kg na dan skupaj z interferonom alfa- 2b v odmerku 3 mio i. e. / m2 trikrat na teden v času enega leta, čemur je sledilo 6- mesečno spremljanje po zdravljenju.
57% male, 80% Caucasian, and 78% genotype 1, 64% ≤ 12 years of age.
V študijo je bilo vključenih 118 bolnikov; od tega je bilo 57% moških, 80% bolnikov bele rase, 78% bolnikov z genotipom 1 in 64% otrok, starih ≤12 let.
The population enrolled mainly consisted in children with mild to moderate hepatitis C.
Populacije je vključevala predvsem otroke z blagim do zmernim hepatitisom C.
Study results are summarized in Table 11.
Povzetek izsledkov študije je podan v Preglednici 11.
Table 11.
Table 11.
Virological response in previously untreated children and adolescents Rebetol 15 mg/kg/day + interferon alfa-2b 3 MIU/m2 3 times a week
Virološki odziv pri predhodno nezdravljenih otrocih in mladostnikih Rebetol 15 mg/ kg na dan + interferon alfa- 2b 3 mio i. e. / m2 3- krat na teden
21 Genotype 2/3/4 (n=26) * Number (%) of patients
Genotip 2/ 3/ 4 (n=26) * Število (%) bolnikov
Ribavirin is absorbed rapidly following oral administration of a single dose (mean Tmax= 1.5 hours), followed by rapid distribution and prolonged elimination phases (single dose half-lives of absorption, distribution and elimination are 0.05, 3.73 and 79 hours, respectively).
Ribavirin se hitro absorbira po zaužitju enkratnega odmerka (srednji Tmax = 1, 5 ure), čemur sledita hitra faza porazdelitve in faze podaljšanega izločanja (razpolovna doba absorpcije, porazdelitve in izločanja po enkratnem odmerku so 0, 05, 3, 73 in 79 ur).
Absorption is extensive with approximately 10% of a radiolabelled dose excreted in the faeces.
Absorpcija zdravila je obsežna.
However, absolute bioavailability is approximately 45 %-65%, which appears to be due to first pass metabolism.
Približno 10% radioaktivno označenega odmerka se izloči z blatom, vendar je absolutna biološka uporabnost zdravila približno 45% do 65%, verjetno zaradi presnove pri prvem prehodu skozi jetra.
Ribavirin has been shown to produce high inter- and intra-subject pharmacokinetic variability following single oral doses (intrasubject variability of approximately 30% for both AUC and Cmax), which may be due to extensive first pass metabolism and transfer within and beyond the blood compartment.
To je lahko posledica obsežne presnove pri prvem prehodu skozi jetra in porazdelitve v okviru krvnega prostora in iz njega.
The ratio of whole blood:plasma ribavirin concentrations is approximately 60: 1; the excess of ribavirin in whole blood exists as ribavirin nucleotides sequestered in erythrocytes.
Razmerje koncentracij ribavirina v polni krvi proti plazmi je približno 60 proti 1; prebitek ribavirina v polni krvi pa je v obliki ribavirinskih nukleotidov, sekvestriranih v eritrocitih.
Ribavirin has two pathways of metabolism:
Ribavirin ima dve presnovni poti:
1) a reversible phosphorylation pathway; 2) a degradative pathway involving deribosylation and amide hydrolysis to yield a triazole carboxyacid metabolite.
1) reverzibilno fosforilacijsko pot ter; 2) razgradno pot, ki obsega deribozilacijo in amidno hidrolizo in tvori triazolski karboksikislinski presnovek.
Following oral dosing with 600 mg BID, steady-state was reached by approximately four weeks, with mean steady state plasma concentrations approximately 2,200 ng/ml.
Po peroralnem odmerjanju ribavirina 600 mg dvakrat na dan je bilo stanje dinamičnega ravnovesja doseženo v približno štirih tednih; srednja plazemska koncentracija v stanju dinamičnega ravnovesja je bila približno 2200 ng/ ml.
Food effect:
Učinek hrane:
The bioavailability of a single oral dose of ribavirin was increased by co-administration of a high fat meal (AUCtf and Cmax both increased by 70%).
Biološka uporabnost enkratnega peroralnega odmerka ribavirina se je povečala ob sočasnem zaužitju zdravila z zelo mastnim obrokom (tako AUCtf kot Cmax sta se povečala za 70%).
Renal function:
Delovanje ledvic:
Single-dose ribavirin pharmacokinetics were altered (increased AUCtf and Cmax) in patients with renal dysfunction compared with control subjects (creatinine clearance > 90 ml/minute).
Pri bolnikih z motnjami delovanja ledvic je bila farmakokinetika ribavirina po enkratnem odmerku spremenjena (povečanje AUCtf in Cmax) glede na kontrolno skupino (očistek kreatinina > 90 ml/ minuto).
Hepatic function:
Delovanje jeter: