Reactome | Ribavirin ADME

Ribavirin ADME

Stable Identifier

R-HSA-9755088

DOI

10.3180/R-HSA-9755088.1

Type

Pathway

Species

Homo sapiens

Compartment

cytosol, extracellular region, plasma membrane

ReviewStatus

5/5

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Ribavirin (RBV) is a synthetic nucleoside analog structurally related to guanine. It is given orally as part of the treatment of HCV infection, and by inhalation for the treatment of RSV infection. According to the WHO, ribavirin can also be used for the treatment of viral hemorrhagic fevers (WHO 2015).
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 (Goodarzi et al, 2016). 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 (Dixit and Perelson, 2006).

Literature References

PubMed ID	Title	Journal	Year
	HIGHLIGHTS OF PRESCRIBING INFORMATION Food and Drug Administration, FDA
26952879	Biowaiver Monographs for Immediate Release Solid Oral Dosage Forms: Ribavirin Polli, JE, Mehta, MU, Langguth, P, Abrahamsson, B, Shah, VP, Goodarzi, N, Groot, DW, Cristofoletti, R, Dressman, JB, Barazesh Morgani, A	J Pharm Sci	2016
16501888	The metabolism, pharmacokinetics and mechanisms of antiviral activity of ribavirin against hepatitis C virus Dixit, NM, Perelson, AS	Cell Mol Life Sci	2006
	World Health Organization model list of essential medicines: 21st list 2019. No. WHO/MVP/EMP/IAU/2019.06 World Health Organization, WHO