リレンザ 化学特性,用途語,生産方法
解説
ザナミビル（zanamivir），抗インフルエンザウイルス薬の一。商品名リレンザ。日本では平成12年（2000）12月に発売され、平成13年（2001）2月に健康保険適用となった。販売元はグラクソ‐スミスクライン。吸入薬で、専用の吸入器を用いてドライパウダーを吸入する。平成20年（2008）から翌年にかけてオセルタミビルの耐性ウイルスが流行したため、需要が高まった。合理的薬物設計によって合成された抗インフルエンザ薬．シアリダーゼを阻害することにより，インフルエンザウイルスの複製を抑制する．分解点256 ℃．[α]20D＋40.9(c ＝ 0.9，H2O)．
用途
ノイラミニダーゼ阻害剤です。
ノイラミニダーゼは糖鎖の末端に結合したシ
アル酸を切り離す作用を有します。宿主細胞
内で増殖したウィルスが、細胞から遊離して
別の細胞に感染するのを阻害します。
効能
抗ウイルス薬, ノイラミニダーゼ阻害薬
商品名
リレンザ (グラクソ・スミスクライン)
説明
Zanamivir was launched as Relenza in Australia for treatment of human
influenza A and B virus infections. Zanamivir (4-guanidino-Neu5Ac2en) can be
obtained by several similar ways, for instance in seven step synthesis starting
from N-acetyI-D-neuraminic acid. Mechanistically, Zanamivir is a potent and
specific inhibitor of neuraminidase (or sialidase), a key viral surface
glycohydrolase essential for viral replication and disease progression by
catalyzing the cleavage of terminal sialic acid residues from the glycoprotein.
The in vitro activity of Zanamivir against a wide variety of influenza A and B
strains was demonstrated in different model systems; its activity against
clinically relevant isolates of influenza virus, with IC50 values ranging from 0.005
to 15 pM was superior to those of amantadine and rimantadine.
化学的特性
Colorless Crystalline Solid
使用
ZANAMIVIR HYDRATE is a sialic acid analog that inhibits neuraminidase release of newly replicated influenza virus particles. It has been shown to selectively inhibit the growth of influenza A and B viruses in plaque reduction assays with IC50 values ranging from 5 to 14 nM and to directly inhibit influenza A and B virus neuraminidases with IC50 values ranging from 0.6 to 7.9 nM in vitro. The efficacy and tolerabilbity of zanamivir has also been established in clinical trial.[Cayman Chemical]
適応症
Zanamivir (Relenza) is a neuraminidase inhibitor with
activity against influenza A and B strains. Like oseltamivir,
zanamivir is a reversible competitive antagonist
of viral neuraminidase. It inhibits the release of
progeny virus, causes viral aggregation at the cell surface,
and impairs viral movement through respiratory
secretions. Resistant variants with hemagglutinin and/or
neuraminidase mutations have been produced in vivo;
however, clinical resistance to zanamivir is quite rare at
present.
獲得抵抗性
Resistance is presently uncommon, including strains resistant
to oseltamivir. In clinical trials the frequency was no more
than 1% of exposed patients.
一般的な説明
Zanamivir is identical to 2-deoxy-2,3-dehydro-N-acetylneuraminic acid except that itpossesses a guanidino group at position 4 instead of a hydroxylgroup. At positions 119 and 227 of the receptor site,there exist glutamic acid residues. Zanamivir has beenshown to form a salt bridge with the guanidine and Glu-119and a charge transfer interaction with Glu-227. These interactionsincrease the interaction strength with the enzymeand create an excellent competitive inhibitor and an effectiveantiviral agent for influenza types A and B.
Human studies have shown that zanamivir is effectivewhen administered before or after exposure to the influenzavirus. If administered before exposure to the virus, the drugreduced viral propagation, infectivity, and disease symptoms.If administered after exposure, the drug reduces propagation,viral titer, and illness. Zanamivir is marketed as a dry powderfor oral inhalation. It is used in adolescents and adults who have been exposed and are symptomatic for not more than 2days. Zanamivir is also indicated for prophylactically treatingfamily members of a person who has developed influenza.
応用例（製薬）
A synthetic neuraminidase inhibitor formulated for administration
by inhalation.
薬理学
Zanamivir is generally well tolerated. Bronchospasm
and impaired lung function have been reported in some
patients taking this medication, but many of these individuals
had serious underlying pulmonary disease.
Zanamivir should be discontinued if an individual develops
bronchospasm or breathing difficulties; treatment
and hospitalization may be required. Allergic reactions,
including angioedema, have been rarely
reported. The efficacy of zanamivir depends upon the
proper use of the inhaler device.
薬物動態学
Oral bioavailability is poor. After inhalation local respiratory
mucosal concentrations greatly exceed those that are inhibitory
for influenza A and B replication. The median concentrations
in the sputum exceed 1 mg/L 6 h after inhalation and
remain detectable for 24 h.
臨床応用
Treatment of influenza A and B infections in patients over 7 years of age,
and prophylaxis of patients ??5 years of age
副作用
Most adverse effects are related to the respiratory tree. These
include rhinorrhea and, rarely, bronchospasm. Nausea and
vomiting have been reported at low incidence.
代謝
Zanamirvir is effective when administered via the nasal, intraperitoneal, and intravenous (IV) routes, but it is inactive when given orally. Animal studies have shown 68% recovery of the drug in the urine following intraperitoneal administration, 43% urinary recovery following nasal administration, and only 3% urinary recovery following oral administration. Human data gave results similar to those obtained in animal models. Human efficacy studies with nasal drops or sprays demonstrated that the drug was effective when administered before and after exposure to influenza A or B virus. When given before viral inoculation, the drug reduced viral shedding, infection, and symptoms. When administered beginning at either 26 or 32 hours after inoculation, there was a reduction in shedding, viral titer, and fever.
リレンザ 上流と下流の製品情報
原材料
臭化シアン
ヒドラジン (無水)
メチルアミン
酢酸ナトリウム
149398-58-3
Carbamimidothioic acid, N-acetyl-, methyl ester
1H-Pyrazole-3-carboximidamide Hydrochloride
D-glycero-D-galacto-Non-2-enonic acid, 5-(acetylamino)-4-[(aminoiminomethyl)amino]-2,6-anhydro-3,4,5-trideoxy-, methyl ester, 7,8,9-triacetate
ザナミビルアミン
三酢酸ザナミビルアミンメチルエステル
1-アミジノピラゾール塩酸塩
(3AR,4R,7AR)-3A,7A-ジヒドロ-2-メチル-4-[(1S,2R)-1,2,3-トリス(アセチルオキシ)プロピル]-4H-ピラノ[3,4-D]オキサゾール-6-カルボン酸メチルエステル
イミノ(アミノ)メタンスルホン酸
準備製品