| Indication |
For the treatment of chronic hepatitis C and for respiratory syncytial virus (RSV). |
| Pharmacodynamics |
Ribavirin is an anti-viral drug active against a number of DNA
and RNA viruses. It is a member of the nucleoside antimetabolite drugs
that interfere with duplication of the viral genetic material. The drug
inhibits the activity of the enzyme RNA dependent RNA polymerase, due to
it's resemblence to building blocks of the RNA molecules. The oral form
is used in the treatment of hepatitis C, in combination with interferon
drugs. The aerosol form is used to treat respiratory syncytial
virus-related diseases in children. The primary serious adverse effect
of ribavirin is hemolytic anemia, which may worsen preexisting cardiac
disease. |
| Mechanism of action |
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. |
| Absorption |
Rapidly and extensively absorbed following oral administration.
However, due to first-pass metabolism, the absolute bioavailability
averages 64%. |
| Volume of distribution |
Not Available |
| Protein binding |
Not Available |
| Metabolism |
Hepatic. Results of in vitro studies using both human and
rat liver microsome preparations indicated little or no cytochrome P450
enzyme-mediated metabolism of ribavirin, with minimal potential for
P450 enzyme-based drug interactions. Ribavirin has two pathways of
metabolism: (1) a reversible phosphorylation pathway in nucleated cells;
and (2) a degradative pathway involving deribosylation and amide
hydrolysis to yield a triazole carboxylic acid metabolite. |
| Route of elimination |
Not Available |
| Half life |
9.5 hours |
| Clearance |
- Apparent cl=26 L/h [A single oral dose]
|
| Toxicity |
Side effects include "flu-like" symptoms, such as headache, fatigue, myalgia, and fever. The LD50
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). |
