Figure 1. The Effect of Ribavirin on Intracellular Concentration of Didanosine's Active Metabolite

Abbreviations: IMP = inosine monophosphate, AMP = adenosine monophosphate, ADP = adenosine diphosphate, ATP = adenosine triphosphate

Ribavirin inhibits IMP dehydrogenase leading to an increase in the IMP pool available to act as a phosphate donor for the transformation of didanosine (ddI) into deoxy IMP (dIMP). The dIMP is then metabolized sequentially into dideoxy AMP (ddAMP), ddADP, and ddATP, the triphosphorylated active metabolite of didanosine. The ddATP inhibits both HIV reverse transcriptase and human mitochondrial DNA polymerase-gamma. The increased intracellular concentration of ddATP may lead to increased mitochondrial toxicity with resultant clinical manifestations of pancreatitis, peripheral neuropathy, and lactic acidosis. This figure is adapted from Salmon-Ceron D, Chauvelot-Moachon L, Abad S, Silbermann B, Sogni P. Mitochondrial toxic effects and ribavirin. Lancet. 2001;357:1803-4. Reproduced with permission from Elsevier.

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