アトバコン 化学特性,用途語,生産方法
外観
うすい黄色～褐色粉末～結晶
効能
抗真菌薬 (ニューモシスチス)
商品名
サムチレール (グラクソ・スミスクライン)
説明
Atovaquone is an orally active antiprotozoal agent indicated for patients with mild to
moderate AIDS-associated Pneumocystis carinii pneumonia who are intolerant to the
fist-line therapy of trimethoprim-sulfamethoxazole. It is also under investigation as a
treatment for malaria and AIDS-associated toxoplasmosis.
化学的特性
Yellow to Orange Crystalline Solid
使用
Atovaquone inhibits the cytochrome bc(1) complex via interactions with the Rieske iron-sulfur protein and cytochrome b in the ubiquinol oxidation pocket. In addition to its use as a treatment for toxoplasmosis, atovaquone has antimalarial properties and prevents pneumocystis pneumonia post-renal transplant.
定義
ChEBI: A naphthoquinone compound having a 4-(4-chlorophenyl)cyclohexyl group at the 2-position and a hydroxy substituent at the 3-position.
抗菌性
It is active against erythrocytic, liver and sexual stages of
malaria parasites. It shows synergy with proguanil and tetracyclines
in vitro. It is also active against Babesia spp. and both
tachyzoites and cysts of Tox. gondii. Pn. jirovecii is sensitive in
vitro at 0.1–3.0 mg/L and high doses are effective in the rat.
獲得抵抗性
Point mutations on parasite cytochrome b, in particular
at codon 268, cause resistance and readily occur when the
drug is used alone. The rapid selection of resistance led to
the development of the synergistic combination with proguanil.
Failure of Pn. jirovecii prophylaxis has also been associated
with cytochrome b mutations.
一般的な説明
Pharmaceutical secondary standards for application in quality control, provide pharma laboratories and manufacturers with a convenient and cost-effective alternative to the preparation of in-house working standards.
Atovaquone belongs to the class of naphthoquinones with a broad-spectrum activity against parasitic infections including malaria, toxoplasmosis and Pneumocystis pneumonia. It is a potent antiprotozoal compound which aids in collapsing the mitochondrial membrane potential in a malaria parasite.
応用例（製薬）
A hydroxynaphthoquinone. Available as the trans isomer
(which is more active than the cis form) for oral use. It is insoluble
in water.
作用機序
Atovaquone is thought to produce its antiparasitic action by virtue of its ability to
inhibit the mitochondrial respiratory chain. More specifically, atovaquone is a ubiquinone
reductase inhibitor, inhibiting at the cytochrome bc1 complex. This action leads to a collapse
of the mitochondrial membrane potential. The compound shows stereospecific inhibition, with the
trans isomer being more active than the cisisomer.
薬物動態学
Oral absorption: Poor
C
max 750 mg oral: 27 mg/L (steady state)
Plasma half-life: 70 h
Plasma protein binding: >99%
It is highly lipophilic and is poorly absorbed from the gastrointestinal
tract following oral administration. Bioavailability is
improved when administered with meals, particularly those
with a high fat content. Steady-state plasma concentrations
are up to 50% lower in AIDS patients than in asymptomatic
HIV-positive cases and the elimination half-life is lower (55 h)
in patients with AIDS. The concentration in CSF is <1% of
the plasma level. Unlike some other naphthoquinones it is not
metabolized by human liver microsomes. Combinations with
co-trimoxazole (in HIV patients) and with proguanil plus
artesunate in healthy adults did not produce any changes in
atovaquone pharmacokinetics.
臨床応用
Pn. jirovecii pneumonia; alternative therapy for mild to moderate illness
(prophylaxis and treatment)
Prophylaxis and treatment of malaria in combination with proguanil
It has also been used in cerebral toxoplasmosis in AIDS
patients and in a few cases of human babesiosis.
副作用
Most clinical trials of atovaquone alone have involved patients
with AIDS in whom adverse effects are often difficult to
detect; however, more than 20% reported fever, nausea, diarrhea
and rashes. There were limited changes in hepatocellular
function. In malaria, in combination with proguanil, there are
few reported side effects.
代謝
Atovaquone is poorly absorbed from the GI tract because of its poor water solubility and high fat
solubility, but the absorption can be significantly increased if taken with a fat-rich meal. The drug
is highly bound to plasma protein (94%) and does not enter the CNS in significant quantities. It is
not significantly metabolized in humans and is exclusively eliminated in feces via the bile.
アトバコン 上流と下流の製品情報
原材料
準備製品