Ribavirin Levels in Post Liver Transplant Patients Treated for Recurrent Hepatitis C Viral Infection

Jain, Ashok; Vekatramanan, Raman; Yelochan, B.; Kashyap, Randeep; Marcos, Amadeo; Fung, John J.

doi:10.1016/j.transproceed.2005.07.057

Cited by 7 publications

(6 citation statements)

References 21 publications

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“…Clinically achievable ribavirin concentrations have been reported to be ≥2.5 µg/ml (28–30). In patients with impaired renal function ribavirin plasma concentrations >100 µg/ml were detected (31). Thus, antiangiogenic concentrations are in the range of therapeutic plasma levels.…”

Section: Discussionmentioning

confidence: 99%

Ribavirin inhibits angiogenesis by tetrahydrobiopterin depletion

Michaelis

Suhan

et al. 2006

FASEB j.

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Ribavirin is a broad-spectrum antiviral drug that is used to treat hepatitis C virus (HCV)-infected patients. The virological response after ribavirin treatment appears to be insufficient to fully explain ribavirin-induced beneficial effects. Angiogenesis plays a pathogenic role in HCV-induced liver damage. Here, we investigated the influence of therapeutic ribavirin concentrations on angiogenesis. Ribavirin inhibited endothelial cell tube formation in vitro and vessel formation in the chick chorioallantoic membrane assay in vivo. Ribavirin inhibits inosine monophosphate dehydrogenase, which causes depletion of cellular GTP and in turn reduction of cellular tetrahydrobiopterin levels. The availability of tetrahydrobiopterin limits NO production by endothelial NO synthase. Ribavirin reduced levels of tetrahydrobiopterin (as revealed by HPLC), NO (as revealed by electron spin resonance spectroscopy), and cGMP (as revealed by RIA) in endothelial cells. Addition of tetrahydrobiopterin or NO prevented ribavirin-induced tube formation inhibition. In conclusion, angiogenesis inhibition by ribavirin has not been described before. This inhibition may contribute to ribavirin-induced pharmacological effects including adverse events.

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Section: Discussionmentioning

confidence: 99%

Ribavirin inhibits angiogenesis by tetrahydrobiopterin depletion

Michaelis

Suhan

et al. 2006

FASEB j.

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“…67 Other trials show significantly different ribavirin concentrations between patients on antiretrovirals and those not on such treatment. 66, 74 To our knowledge, there are no published data that examine the effect of ribavirin TDM versus ribavirin dose adjustment using laboratory values or clinical signs and symptoms on rates of SVR in this patient population. Given that HIV-HCV coinfected patients with genotype 2 or 3 can achieve SVR up to 67% (similar to HCV mono-infected patients) 48 and that there is a discrepancy between studies in the concentration-virologic response relationship, TDM of ribavirin in HIV-HCV coinfected patients may not be needed.…”

Section: Hiv Coinfectionmentioning

confidence: 99%

“…76 Conversely, there are also trials demonstrating that no dose-response correlation exists, and thus suggesting that measurement of ribavirin concentrations (ie, TDM) may be of use. [73][74][75] Consequently, based on the available evidence, it is uncertain whether TDM of ribavirin in liver transplant patients offers benefits in increasing rate of SVR or decreasing incidence of anemia.…”

Section: Liver Transplantmentioning

confidence: 99%

The Utility of Therapeutic Drug Monitoring for Ribavirin in Patients with Chronic Hepatitis C—A Critical Review

2009

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“…Perhaps, with larger sample size, an association between creatinine clearance and anemia would also have been shown. In clinical practice, ribavirin dosing is adjusted for creatinine clearance because of the known associations between decreased creatinine clearance and increased risk of hemolytic anemia 59–63. Thus, there may have been a bias in our center to use lower doses of ribavirin in patients with renal insufficiency.…”

Section: Discussionmentioning

confidence: 99%