Ribavirin ADME

RBV is administered orally in doses of 400 to 600 mg. It is highly soluble in water and a typical dose is dissolved completely over a wide range of acidities. RBV is rapidly absorbed into the circulation. After the oral administration of 600 mg radiolabeled ribavirin, approximately 61% of the drug was detected in the urine and 12% was detected in the feces. 17% of an administered dose was in unchanged form. RBV accumulates in human erythrocytes and remains in the body for weeks, with a halflife of >100 hours. A consequence of the accumulation in erythrocytes is the well-known side effect of hemolytic anemia, which is reversible by cessation of administration (FDA label Rebetol, 2013).

Ribavirin is a prodrug. It is metabolized through two different paths: phosphorylation, yielding the active triphosphate (RBV-TP), and degradation via de-ribosylation and hydrolysis of the amide group. The GI tract, and not the liver, appears to be the major site of first-pass elimination.