Optimizing peginterferon and ribavirin administration in difficult-to-treat patient populations

Landaverde, Carmen; Saab, Sammy

doi:10.1007/s11901-009-0007-9

Cited by 2 publications

(2 citation statements)

References 67 publications

(81 reference statements)

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“…exposure to ribavirin without rendering anaemia intolerable [8,25,[38][39][40][41][42]. Several previous studies have emphasized the need for personalizing and regular monitoring of ribavirin exposure during the treatment of chronic hepatitis C [25,39,40,42,43].…”

Section: Discussionmentioning

confidence: 99%

“…Adherence to ribavirin is compromised, however, by its side effect, haemolytic anaemia, which in turn lowers response. Significant efforts are underway, therefore, to identify optimal dosing protocols that would ensure adequate exposure to ribavirin without rendering anaemia intolerable [8,25,[38][39][40][41][42]. Several previous studies have emphasized the need for personalizing and regular monitoring of ribavirin exposure during the treatment of chronic hepatitis C [25,39,40,42,43].…”

Section: Discussionmentioning

confidence: 99%

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A Formula to Estimate the Optimal Dosage of Ribavirin for the Treatment of Chronic Hepatitis C: Influence of Itpa Polymorphisms

Krishnan

Dixit

2012

Antiviral Therapy

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A Formula to Estimate the Optimal Dosage of Ribavirin for the Treatment of Chronic Hepatitis C: Influence of Itpa Polymorphisms

Krishnan

Dixit

2012

Antiviral Therapy

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Ribavirin-Induced Anemia in Hepatitis C Virus Patients Undergoing Combination Therapy

Krishnan

Dixit

2011

PLoS Comput Biol

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The current standard of care for hepatitis C virus (HCV) infection – combination therapy with pegylated interferon and ribavirin – elicits sustained responses in only ∼50% of the patients treated. No alternatives exist for patients who do not respond to combination therapy. Addition of ribavirin substantially improves response rates to interferon and lowers relapse rates following the cessation of therapy, suggesting that increasing ribavirin exposure may further improve treatment response. A key limitation, however, is the toxic side-effect of ribavirin, hemolytic anemia, which often necessitates a reduction of ribavirin dosage and compromises treatment response. Maximizing treatment response thus requires striking a balance between the antiviral and hemolytic activities of ribavirin. Current models of viral kinetics describe the enhancement of treatment response due to ribavirin. Ribavirin-induced anemia, however, remains poorly understood and precludes rational optimization of combination therapy. Here, we develop a new mathematical model of the population dynamics of erythrocytes that quantitatively describes ribavirin-induced anemia in HCV patients. Based on the assumption that ribavirin accumulation decreases erythrocyte lifespan in a dose-dependent manner, model predictions capture several independent experimental observations of the accumulation of ribavirin in erythrocytes and the resulting decline of hemoglobin in HCV patients undergoing combination therapy, estimate the reduced erythrocyte lifespan during therapy, and describe inter-patient variations in the severity of ribavirin-induced anemia. Further, model predictions estimate the threshold ribavirin exposure beyond which anemia becomes intolerable and suggest guidelines for the usage of growth hormones, such as erythropoietin, that stimulate erythrocyte production and avert the reduction of ribavirin dosage, thereby improving treatment response. Our model thus facilitates, in conjunction with models of viral kinetics, the rational identification of treatment protocols that maximize treatment response while curtailing side effects.

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Optimizing peginterferon and ribavirin administration in difficult-to-treat patient populations

Cited by 2 publications

References 67 publications

A Formula to Estimate the Optimal Dosage of Ribavirin for the Treatment of Chronic Hepatitis C: Influence of Itpa Polymorphisms

A Formula to Estimate the Optimal Dosage of Ribavirin for the Treatment of Chronic Hepatitis C: Influence of Itpa Polymorphisms

Ribavirin-Induced Anemia in Hepatitis C Virus Patients Undergoing Combination Therapy

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