title: Assessment of adverse reactions and pharmacokinetics of ribavirin in combination with interferon alpha-2b in patients with chronic hepatitis C.
abstract: Ribavirin has recently been demonstrated to be efficacious in combination with interferon (IFN) alpha-2b for the treatment of relapsed hepatitis C infections. The aim of this study was to evaluate the relationship between the pharmacokinetics and adverse reactions of ribavirin when ribavirin plus IFN alpha-2b were administered to patients affected with chronic hepatitis C. Nineteen patients received intramuscular IFN alpha-2b at a dose of 6 or 10 million units and oral ribavirin at 600 mg or 800 mg daily for 24 weeks. The pharmacokinetic profiles of ribavirin were assessed by the measurement of plasma concentrations. Twelve patients were continuously given both ribavirin and IFN alpha-2b, whereas in 7 patients the therapy was discontinued due to severe adverse drug reactions such as skin eruption, anemia and depression. There were no significant differences in ribavirin dose, Hb, ALT and AST values between the continued and the discontinued therapy groups. In contrast, the pretreatment platelet level and patient age of the discontinued therapy group were significantly different to the continued group. The trough plasma concentration of ribavirin in the discontinued therapy group was significantly higher than that in the continued group at week 1. These results suggest that the monitoring of plasma ribavirin concentrations may be valid for predicting the early phase of adverse drug reactions, thereby providing useful information for the adjustment of the ribavirin dosing for each patient.
authors.affiliation: Department of Pharmacy, Kumamoto University Hospital, Kumamoto, Japan.
authors.forename: Misako
authors.initials: M
authors.lastname: Uchida
authors.forename: Akinobu
authors.initials: A
authors.lastname: Hamada
authors.forename: Masafumi
authors.initials: M
authors.lastname: Yamasaki
authors.forename: Shigetoshi
authors.initials: S
authors.lastname: Fujiyama
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Sasaki
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Saito
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism; D000998:Antiviral Agents / Q000009:adverse effects* / Q000493:pharmacokinetics*; D004359:Drug Therapy, Combination; D005260:Female; D006454:Hemoglobins / Q000378:metabolism; D019698:Hepatitis C, Chronic / Q000378:metabolism*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects* / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D010976:Platelet Count; D011994:Recombinant Proteins; D012254:Ribavirin / Q000009:adverse effects* / Q000493:pharmacokinetics*
chemical_list: D000998:Antiviral Agents; D006454:Hemoglobins; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D012254:Ribavirin