Study of the Pharmacokinetic Action of Amantadine and Ribavirin in Chronic Hepatitis C. CINAM

The study is conducted in naive patients infected with genotype non 2 non 3 administered peginterferon alpha 2-a (40KD) weekly, and ribavirin with dose adjusted on BW (< 75 kg 1000 mg/day, >75 kg 1200 mg/day) for the first three months with adjunction of amantadine 200 mg daily for the following 9 months.

Plasma concentration profiles of ribavirin were studied after the first dose (D0) and at W12. At each period, blood samples were collected pre-dose and 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, and 10 hours post-dosing. Ribavirin concentrations were measured using liquid chromatography-tandem mass spectrometry and ribavirin area under the concentration-timcurves (AUC0-10h) were derived from plasma concentrations profiles using the linear trapezoidal rule.

Virological follow-up was performed at W2, W4, W6, W8, W12, W24 and W72. Early virological response was defined by undetectable viral load at W12.

Inclusion criteria

• Male and female patients >18 years of age and <65 years of age
• Génotype non2 non3
• Chronic liver disease consistent with chronic hepatitis C infection on a biopsy (obtained within the past 24 months) as judged by a local pathologist (Metavir >A1and >F1)
• Negative urine or blood pregnancy test (for women of childbearing potential) documented within the 24-hour period prior to the first dose of study drug

Exclusion criteria

• Women with ongoing pregnancy or breast feeding
• IFN or ribavirin therapy at any previous time
• Positive test at screening for anti-HAV IgM Ab, HBsAg, anti-HBc IgM Ab, anti-HIV Ab
• History or other evidence of a medical condition associated with chronic liver disease other than HCV (e.g., hemochromatosis, autoimmune hepatitis, metabolic liver disease, alcoholic liver disease, toxin exposures)
• Serum creatinine level >1.5 times the upper limit of normal at screening
• History of severe psychiatric disease, especially depression