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Ribavirin
- indication:For the treatment of chronic hepatitis C and for respiratory syncytial virus (RSV).
- pharmacologypharmacology:
- mechanism: Ribavirin is readily phosphorylated intracellularly by adenosine kinase to ribavirin mono-, di-, and triphosphate metabolites. Ribavirin triphosphate (RTP) is a potent competitive inhibitor of inosine monophosphate (IMP) dehydrogenase, viral RNA polymerase and messenger RNA (mRNA) guanylyltransferase (viral) and can be incorporated into RNA in RNA viral species.. Guanylyltranserase inhibition stops the capping of mRNA. These diverse effects result in a marked reduction of intracellular guanosine triphosphate (GTP) pools and inhibition of viral RNA and protein synthesis. Ribavirin is also incorporated into the viral genome causing lethal mutagenesis and a subsequent decrease in specific viral infectivity.
- toxicity: Side effects include "flu-like" symptoms, such as headache, fatigue, myalgia, and fever. The LD<sub>50</sub> in mice is 2 g/kg orally and is associated with hypoactivity and gastrointestinal symptoms (estimated human equivalent dose of 0.17 g/kg, based on body surface area conversion).
- absorprion: Rapidly and extensively absorbed following oral administration. However, due to first-pass metabolism, the absolute bioavailability averages 64%.
- halflife: 9.5 hours
- roouteelimination:
- volumedistribution:
- clearance: * Apparent cl=26 L/h [A single oral dose]