Ribavirin and cellular ribavirin‐triphosphate concentrations in blood and bronchoalveolar lavage fluid in two lung transplant patients with respiratory syncytial virus

Abstract

Respiratory syncytial virus (RSV) is responsible for significant morbidity and mortality in the lung transplant population. Oral and aerosolized ribavirin may improve outcomes in lung transplant patients with RSV; however, data relating ribavirin concentrations in plasma and intracellular ribavirin triphosphate (iRTP) concentrations in blood and bronchoalveolar lavage (BAL) fluid cells with efficacy and safety are lacking. We describe ribavirin and iRTP concentrations within various compartments in two adult lung transplant recipients with RSV who were sampled throughout successful treatment courses with oral and inhaled ribavirin. In patient 1, iRTP BAL concentrations decreased by 45% over 3 days after changing inhaled ribavirin to oral (6.32 to 3.43 pmol/106 cells). In patient 2, iRTP BAL concentrations were 103 pmol/106 cells after 5 days of oral followed by 5 days of inhaled ribavirin. Further study is needed to describe ribavirin pharmacokinetics in the respiratory compartment to inform clinical use of ribavirin for respiratory viruses.

Effects of the 5′‐Triphosphate Metabolites of Ribavirin, Sofosbuvir, Vidarabine, and Molnupiravir on CTP Synthase Catalysis and Filament Formation: Implications for Repurposing Antiviral Agents against SARS‐CoV‐2

“…Considering that the concentration of RBV−TP in the red blood cells and bronchoalveolar lavages from patients with respiratory syncytial virus were 313 μM and 514 μM, respectively, [40] it is possible that RBV−TP could replace GTP as a weak allosteric activator of CTPS, thereby furnishing a mechanism by which CTPS can remain active. Although the overall efficiency of activation ( k act / K A ) by RBV−TP is ∼24‐fold less than that of GTP, the allosteric activation of Ec CTPS by RBV−TP suggests a mechanism for the continued production of CTP despite the depletion of the GTP pools arising from the inhibition of IMPDH by ribavirin‐5′‐monophosphate upon ribavirin treatment [34a,37] …”