リバビリン 化學(xué)特性,用途語,生産方法
外観
白色～ほとんど白色粉末～結(jié)晶
用途
ウィルス RNA ポリメラーゼ
を阻害し、ウィルスの増殖阻害作用を示しま
す。
用途
リバビリン（Ribavirin）は、抗ウイルス薬の一つで、主にC型肝炎やウイルス性出血熱等の治療で施行されている。
効能
抗ウイルス薬
商品名
コペガス (中外製薬); レベトール (MSD)
化學(xué)的特性
Colourless Solid
使用
Ribavirin is a guanosine analog with antiviral properties against DNA and RNA viruses, including respiratory syncytial virus, hepatitis C, and influenza. It acts as a prodrug that can be activated by either mono- or tri-phosphorylation by cellular kinases. These phosphorylated derivatives of ribavirin have diverse effects on both cellular and viral enzymes, resulting in suppression of viral replication.
定義
ChEBI: A 1-ribosyltriazole that is the 1-ribofuranosyl derivative of 1,2,4-triazole-3-carboxamide. An inhibitor of HCV polymerase.
適応癥
Ribavirin is a synthetic guanosine analogue that possesses
broad antiviral inhibitory activity against many
viruses, including influenza A and B, parainfluenza,RSV,
HCV, HIV-1, and various herpesviruses, arenaviruses,
and paramyxoviruses. Its exact mechanism of action has
not been fully elucidated; however, it appears to inhibit
the synthesis of viral mRNA through an effect on nucleotide
pools. Following absorption, host cell enzymes
convert ribavirin to its monophosphate, diphosphate,
and triphosphate forms. Ribavirin monophosphate inhibits the guanosine triphosphate (GTP) synthesis
pathway and subsequently inhibits many GTP-dependent
processes. Ribavirin triphosphate inhibits the 5 capping
of viral mRNA with GTP and specifically inhibits
influenza virus RNA polymerase. Ribavirin may also
act by increasing the mutation rate of RNA viruses, leading
to the production of nonviable progeny virions.
Ribavirin resistance has not been documented in clinical
isolates.
獲得抵抗性
Development of resistant virus strains has not been
demonstrated.
一般的な説明
Ribavirin is 1-β-D-ribofuranosyl-1,2,4-thiazole-3-carboxamide.The compound is a purine nucleoside analog with amodified base and a D-ribose sugar moiety.
Ribavirin inhibits the replication of a very wide variety ofRNA and DNA viruses,68 including orthomyxoviruses,paramyxoviruses, arenaviruses, bunyaviruses, herpesviruses,adenoviruses, poxvirus, vaccinia, influenza virus(types A and B), parainfluenza virus, and rhinovirus. In spiteof the broad spectrum of activity of ribavirin, the drug hasbeen approved for only one therapeutic indication—thetreatment of severe lower respiratory infections caused byRSV in carefully selected hospitalized infants and youngchildren.
空気と水の反応
Water soluble.
反応プロフィール
Ribavirin may be sensitive to prolonged exposure to light.
危険性
Mildly toxic by ingestion. An experimental
teratogen.
火災(zāi)危険
Flash point data for Ribavirin are not available; however, Ribavirin is probably combustible.
応用例（製薬）
A synthetic nucleoside. It is neither a classic pyrimidine nor a
purine, but stereochemical studies indicate that it is a guanosine
analog. It is usually formulated for administration by inhalation,
but oral and intravenous preparations are also used.
作用機序
Ribavirin, a guanosine analogue, has broad-spectrum antiviral activity against both DNA and RNA viruses. It is phosphorylated by adenosine kinase to the triphosphate, resulting in the inhibition of viral
specific RNA polymerase, disrupting messenger RNA and nucleic acid synthesis.
薬理學(xué)
Oral and intravenous ribavirin are associated with
additional adverse effects.When given via these routes,
ribavirin can produce hemolytic anemia that is reversible
following dosage reduction or cessation of therapy.
When given in combination with interferon- , ribavirin
increases the incidence of many of its side effects,
such as fatigue, nausea, insomnia, depression, and anemia,
and may cause fatal or nonfatal pancreatitis.
Ribavirin is mutagenic, teratogenic, and embryotoxic in
animals at doses below the therapeutic level in humans.
It is contraindicated in pregnant women and in the male
partners of pregnant women. Women of childbearing
potential and male partners of these women must use
two effective forms of contraception during ribavirin
treatment and for 6 months post therapy. Pregnant
women should not directly care for patients receiving
ribavirin.
臨床応用
Ribavirin aerosol (Virazole) is indicated in the treatment
of high-risk infants and young children with severe
bronchiolitis or pneumonia due to RSV infection.
Treatment is most effective if begun within 3 days of the
onset of symptoms.
Although ribavirin monotherapy is ineffective
against HCV, oral ribavirin in combination with interferon-α
(Rebatron) is approved for this indication and is
effective in patients resistant to interferon therapy
alone. Intravenous ribavirin may be useful in the therapy
of Hantaan virus infection, Crimean or Congo virus
hemorrhagic fever, Lassa fever, and severe adenovirus
infection.
副作用
Most adverse effects associated with aerosol ribavirin
are local. Pulmonary function may decline if aerosol ribavirin
is used in adults with chronic obstructive lung disease
or asthma. Deterioration of pulmonary and cardiovascular
function has also been seen in severely ill
infants given this preparation. Rash, conjunctivitis, and
rare cases of anemia have been reported. Health care
workers exposed to aerosol ribavirin during its administration
have reported adverse effects including headache,
conjunctivitis, rash, and rarely, bronchospasm.
リバビリン 上流と下流の製品情報
原材料
準備製品
6-ベンジルアミノプリン 塩酸塩
ribavirin 2',3',5'-triacetate
1-[3,5-O-[1,1,3,3-Tetrakis(1-Methylethyl)-1,3-disiloxanediyl]-β-D-ribofuranosyl]-1H-1,2,4-triazole-3-carboxaMide
2',3'-Isopropylidene Ribavirin