プログアニル

危険有害性情報のコード(GHS)

• 絵表示(GHS)

  

• 注意喚起語

  Warning

• 危険有害性情報

  H302：飲み込むと有害

  H315：皮膚刺激

  H319：強い眼刺激

  H335：呼吸器への刺激のおそれ

• 注意書き

  P261：粉じん/煙/ガス/ミスト/蒸気/スプレーの吸入を避ける こと。

  P280：保護手袋/保護衣/保護眼鏡/保護面を着用するこ と。

  P301+P312：飲み込んだ場合：気分が悪い時は医師に連絡する こと。

  P302+P352：皮膚に付着した場合：多量の水と石鹸で洗うこと。

  P305+P351+P338：眼に入った場合：水で数分間注意深く洗うこと。次にコ ンタクトレンズを着用していて容易に外せる場合は外す こと。その後も洗浄を続けること。

プログアニル 化学特性,用途語,生産方法

• 効能

  抗マラリア薬

• 説明

  Chloroguanide is active with respect to exoerythrocyte and erythrocyte forms of plasmodia. It is most beneficial for suppressive therapy. It is used for preventing malaria, and it should be started 2 weeks before entering a malarial zone and should be taken for 8 weeks. Synonyms of this drug are biguanide, bigunal, paludrine, proguanil, and others.

• 使用

  Proguanil is medicaments; used in preparation of pyrrolecarboxamide derivatives as anti-malarial agents.

• 適応症

  Chloroguanide hydrochloride (Paludrine) is activated to a triazine metabolite, cycloguanil, which also interferes with parasite folic acid synthesis. It is a dihydrofolate reductase inhibitor that is used for the prophylaxis of malaria caused by all susceptible strains of plasmodia. Chloroguanide is rapidly absorbed from the gastrointestinal tract. Peak plasma levels occur 2 to 4 hours after oral administration, and the drug is excreted in the urine with an elimination half-life of 12 to 21 hours. Its side effects and spectrum of antimalarial activity are quite similar to those of pyrimethamine.The conversion of chloroguanide to the active metabolite is decreased in pregnancy and also as a result of genetic polymorphism in 3% of whites and Africans and 20% of Asians.

• 定義

  ChEBI: A biguanide compound which has isopropyl and p-chlorophenyl substituents on the terminal N atoms. A prophylactic antimalarial drug, it works by inhibiting the enzyme dihydrofolate reductase, which is involved in the reproduction of the malaria parasites Plasmodium falciparum and P. vivax within the red blood cells.

• 抗菌性

  Proguanil has low antiplasmodial action, but useful activity is attributable to the metabolite cycloguanil, which inhibits the early erythrocytic stages of all four Plasmodium spp. that cause human malaria and the primary hepatic stage of P. falciparum. Proguanil acts synergistically with atovaquone and probably enhances its effect on mitochondrial membrane charge.

• 獲得抵抗性

  Resistance of P. falciparum associated with point mutations of dihydrofolate reductase has been reported worldwide. Resistance in P. vivax and P. malariae has been reported in South East Asia. Cross-resistance with pyrimethamine is not absolute, because differential resistance can arise from different point mutations on the dihydrofolate reductase gene.

• 応用例（製薬）

  A synthetic arylbiguanide, formulated as the hydrochloride for oral use. It is slightly soluble in water.

• 薬物動態学

  Oral absorption: >90%
  C_max 100 mg oral: 0.4 mg/L after 2–4 h
  Plasma half-life: 10 h
  Plasma protein binding: 75%
  Oral absorption is slow. It is 75% protein bound and is concentrated 10- to 15-fold by erythrocytes. About 20% of the drug is metabolized to dihydrotriazene derivatives, most importantly cycloguanil,by hepatic cytochrome P₄₅₀ processes. Cycloguanil is detectable 2 h after administration of proguanil. High proportions of ‘non-metabolizers’ have been identified in Japan and Kenya, indicating another source of resistance. About 60% of the dose is excreted in the urine.

• 臨床応用

  Antimalarial prophylaxis (usually in combination with chloroquine)
  Treatment and prophylaxis for drug-resistant falciparum malaria (in combination with atovaquone)

• 副作用

  It is well tolerated at recommended doses. Gastrointestinal and renal effects have been reported at doses exceeding 600 mg per day.

• 安全性プロファイル

  Poison by ingestion, intravenous, and intraperitoneal routes. Experimental reproductive effects. When heated to decomposition it emits toxic fumes of Cland NOx.

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