Total clearance (CL/F) of ribavirin is the factor most influencing incidence of hemolytic anemia in interferon .ALPHA. plus ribavirin combination therapy

成司, 豊田; 吉康, 狩野; 淳, 赤池; 卓味, 大村; 隆啓, 佐藤; 克, 山崎; 靖昭, 桑田; 四郎, 飯野

doi:10.2957/kanzo.46.107

Kanzo

2005

DOI: 10.2957/kanzo.46.107

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Total clearance (CL/F) of ribavirin is the factor most influencing incidence of hemolytic anemia in interferon .ALPHA. plus ribavirin combination therapy

豊田成司¹,

狩野吉康²,

赤池淳³

et al.

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Cited by 4 publications

(2 citation statements)

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“…Kamar et al (16) recently demonstrated that RBV apparent clearance (CL/F) is a good marker for determining RBV clearance in HCV-positive transplant patients with normal or impaired renal function. Toyota et al (45) reported that discontinuation of RBV and decrease in hemoglobin concentration depended on CL/F levels.…”

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confidence: 99%

“…Renal function was assessed by serum creatinine (Cr) concentration (mg/dl) and Cr clearance (CrCl; ml/min). RBV apparent clearance was obtained from the formula CL/F (liter/h) ϭ 32.3 ϫ (body weight [kg]) ϫ (1 Ϫ 0.0094 ϫ age) ϫ (1 Ϫ 0.42 ϫ gender [M ϭ 0, F ϭ 1])/Cr (mol/liter), according to previous reports (16,45).Treatment regimen. Patients received 6 million units (MU) of intramuscular IFN-␣2b (IntronA; Schering-Plough, Kenilworth, NJ) daily for 2 weeks and three times a week for 22 weeks.…”

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Role of Erythrocytes as a Reservoir for Ribavirin and Relationship with Adverse Reactions in the Early Phase of Interferon Combination Therapy for Chronic Hepatitis C Virus Infections

et al. 2006

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We investigated the relationship between serum ribavirin concentrations and clearance, as well as therapeutic efficacy and adverse reactions, in 97 Japanese patients with chronic hepatitis C virus infections treated with a 6-month course of high-dose alpha2b interferon (6 million units/day) plus ribavirin (600 to 800 mg/day) combination therapy. This randomized trial showed that the saturation of ribavirin uptake after taking ribavirin capsules does not occur within a dose range of 600 to 800 mg/day, which is a standard dosage used clinically in Japan. Serum ribavirin concentrations and clearance did not correlate with sustained virological response rates. Fourteen patients discontinued therapy because of adverse reactions, and sustained virological response rates were significantly reduced by discontinuation of therapy, while dose reduction of ribavirin did not alter the therapeutic effects. Ribavirin concentrations after 1 week and ribavirin clearance were significantly correlated with discontinuation of ribavirin; however, a multiple-regression analysis revealed that only hemoglobin concentration, but not ribavirin clearance, was a significant factor for discontinuation of therapy (odds ratio, 0.514; 95% confidence interval, 0.311 to 0.85; P ‫؍‬ 0.0095). It appears that peripheral erythrocytes may act as a reservoir for ribavirin and regulate serum ribavirin levels in the very early phase of treatment.It is estimated that 170 million people are infected with hepatitis C virus (HCV) worldwide, and the prevalence is 1% to 2% in developed countries (12,17). The natural history of hepatitis C involves the gradual progression to liver cirrhosis, with hepatocellular carcinoma as a final complication (44). The goal of therapy is to halt or decrease the progression of liver fibrosis (38), and interferon (IFN) therapy has been used for this purpose for more than a decade (33, 34). However, IFN-␣ and -␤ monotherapy is effective in a limited number of patients, with only 10% to 30% of patients experiencing a sustained virological response (SVR) to monotherapy (1,10,36,37). Many investigators, including our group, have tried alternative approaches to enhance SVR rates (5, 9), and based on these investigations, oral ribavirin (RBV) combination therapy is now a first-line treatment (2, 42). Recently, the pegylated form of IFN (PEG-IFN) was demonstrated to be significantly more effective in achieving SVRs than IFN combination therapy (23), and as a result, PEG-IFN and RBV combination therapy has been recently recommended as a standard therapy for HCV infection.Several types of adverse reactions have been reported in patients undergoing antiviral therapy for chronic hepatitis C (35). In recipients of combination therapy, consisting of either standard IFN or PEG-IFN with RBV, hemolytic anemia (hemoglobin concentration of Ͻ100 g/liter) occurred frequently and led to dosage reduction or discontinuation of RBV treatment in 1% to 15% of patients (21,43). Most patients treated with IFN plus RBV combination therapy experience a dec...

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Role of Erythrocytes as a Reservoir for Ribavirin and Relationship with Adverse Reactions in the Early Phase of Interferon Combination Therapy for Chronic Hepatitis C Virus Infections

et al. 2006

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Nadir platelet and neutrophil counts during the course of PEG-IFN α-2b plus ribavirin combination therapy can be predicted by the values at week one: Towards achieving better efficacy

吉康¹,

成司²,

智宏³

et al. 2008

Kanzo

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A case of chronic hepatitis C in which a 72-week course of pegylated interferon and ribavirin combination therapy resulted in relapse but a subsequent interferon monotherapy could induce sustained virological response

千晃¹,

大輔²,

稔³

et al. 2008

Kanzo

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Total clearance (CL/F) of ribavirin is the factor most influencing incidence of hemolytic anemia in interferon .ALPHA. plus ribavirin combination therapy

Cited by 4 publications

References 29 publications

Role of Erythrocytes as a Reservoir for Ribavirin and Relationship with Adverse Reactions in the Early Phase of Interferon Combination Therapy for Chronic Hepatitis C Virus Infections

Role of Erythrocytes as a Reservoir for Ribavirin and Relationship with Adverse Reactions in the Early Phase of Interferon Combination Therapy for Chronic Hepatitis C Virus Infections

Nadir platelet and neutrophil counts during the course of PEG-IFN α-2b plus ribavirin combination therapy can be predicted by the values at week one: Towards achieving better efficacy

A case of chronic hepatitis C in which a 72-week course of pegylated interferon and ribavirin combination therapy resulted in relapse but a subsequent interferon monotherapy could induce sustained virological response

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