AIMS: To evaluate whether higher doses of peginterferon alpha-2a (40KD) [PEG-IFN alpha-2a (40KD)] can compensate for lower exposure observed among obese patients with chronic hepatitis C (CHC) treated with the standard dose of PEG-IFN alpha-2a (40KD). METHODS:Noncirrhotic, obese (body mass index > or =30 kg m(-2)) patients with CHC participated in a single-centre, open-label study. Patients were randomized to 180 or 270 microg week(-1) PEG-IFN alpha-2a (40KD) + ribavirin (1000/1200 mg day(-1)) for 48 weeks. Blood samples were collected predose and up to 168 h after the first dose and at week 12 for pharmacokinetic analysis. Trough serum concentrations (C(trough)) were determined up to week 24. RESULTS: In the 180 microg week(-1) group mean +/- SD steady-state (week 12) estimates of AUC(0-168) (ng h(-1) ml(-1)), C(max) (ng ml(-1)) and CL/F (l h(-1)) were 2154 +/- 919, 13.8 +/- 6.7 and 0.102 +/- 0.051, respectively. In the 270 microg week(-1) group, estimates were 3374 +/- 1844, 23.4 +/- 10.7 and 0.090 +/- 0.042, respectively. The mean (range) C(trough) (ng ml(-1)) was 11.2 (4.4-18.5) in the 180 microg week(-1) group and 16.1 (0.4-44.2) in the 270 microg week(-1) group. Overall, 14 of 20 (70%) and 16 of 20 (80%) patients in the 180 microg week(-1) and 270 microg week(-1) groups were infected with hepatitis C virus genotype 1 or 4. In the 180 microg week(-1) and 270 microg week(-1) groups 14 of 20 (70%) and 15 of 19 (79%) patients, respectively, achieved a sustained viral response. Safety was similar between groups. CONCLUSIONS: Mean PEG-IFN alpha-2a (40KD) exposure was dose proportional from 180 to 270 microg week(-1). Increasing PEG-IFN alpha-2a (40KD) from 180 to 270 microg week(-1) achieves higher serum drug exposure in obese patients.
RCT Entities:
AIMS: To evaluate whether higher doses of peginterferon alpha-2a (40KD) [PEG-IFN alpha-2a (40KD)] can compensate for lower exposure observed among obesepatients with chronic hepatitis C (CHC) treated with the standard dose of PEG-IFN alpha-2a (40KD). METHODS: Noncirrhotic, obese (body mass index > or =30 kg m(-2)) patients with CHC participated in a single-centre, open-label study. Patients were randomized to 180 or 270 microg week(-1) PEG-IFN alpha-2a (40KD) + ribavirin (1000/1200 mg day(-1)) for 48 weeks. Blood samples were collected predose and up to 168 h after the first dose and at week 12 for pharmacokinetic analysis. Trough serum concentrations (C(trough)) were determined up to week 24. RESULTS: In the 180 microg week(-1) group mean +/- SD steady-state (week 12) estimates of AUC(0-168) (ng h(-1) ml(-1)), C(max) (ng ml(-1)) and CL/F (l h(-1)) were 2154 +/- 919, 13.8 +/- 6.7 and 0.102 +/- 0.051, respectively. In the 270 microg week(-1) group, estimates were 3374 +/- 1844, 23.4 +/- 10.7 and 0.090 +/- 0.042, respectively. The mean (range) C(trough) (ng ml(-1)) was 11.2 (4.4-18.5) in the 180 microg week(-1) group and 16.1 (0.4-44.2) in the 270 microg week(-1) group. Overall, 14 of 20 (70%) and 16 of 20 (80%) patients in the 180 microg week(-1) and 270 microg week(-1) groups were infected with hepatitis C virus genotype 1 or 4. In the 180 microg week(-1) and 270 microg week(-1) groups 14 of 20 (70%) and 15 of 19 (79%) patients, respectively, achieved a sustained viral response. Safety was similar between groups. CONCLUSIONS: Mean PEG-IFN alpha-2a (40KD) exposure was dose proportional from 180 to 270 microg week(-1). Increasing PEG-IFN alpha-2a (40KD) from 180 to 270 microg week(-1) achieves higher serum drug exposure in obesepatients.
Authors: K Bjøro; H Bell; K B Hellum; K Skaug; N Raknerud; P Sandvei; B Døskeland; A Maeland; S Lund-Tønnesen; B Myrvang Journal: Scand J Gastroenterol Date: 2002-02 Impact factor: 2.423
Authors: M P Manns; J G McHutchison; S C Gordon; V K Rustgi; M Shiffman; R Reindollar; Z D Goodman; K Koury; M Ling; J K Albrecht Journal: Lancet Date: 2001-09-22 Impact factor: 79.321
Authors: Michael W Fried; Mitchell L Shiffman; K Rajender Reddy; Coleman Smith; George Marinos; Fernando L Gonçales; Dieter Häussinger; Moises Diago; Giampiero Carosi; Daniel Dhumeaux; Antonio Craxi; Amy Lin; Joseph Hoffman; Jian Yu Journal: N Engl J Med Date: 2002-09-26 Impact factor: 91.245
Authors: Stephanos J Hadziyannis; Hoel Sette; Timothy R Morgan; Vijayan Balan; Moises Diago; Patrick Marcellin; Giuliano Ramadori; Henry Bodenheimer; David Bernstein; Mario Rizzetto; Stefan Zeuzem; Paul J Pockros; Amy Lin; Andrew M Ackrill Journal: Ann Intern Med Date: 2004-03-02 Impact factor: 25.391