Сульфадоксин

Описание

Sulfadoxin is a sulfonamide antibiotic that inhibits dihydropteroate synthetase (DHPS), an enzyme involved in folic acid synthesis. Sulfadoxin competes with 4-aminobenzoate (PABA), the native substrate of DHPS, and inhibits PABA incorporation into folic acid. Folate is essential for purine and pyrimidine synthesis, therefore, sulfadoxin has antiproliferative activity in non-resistant P. falciparum. Sulfadoxin inhibits growth of P. falciparum in vitro, but potency varies between non-resistant (IC₅₀ = 4 ng/ml) and resistant strains (IC₅₀ = 3,970 ng/ml).

Химические свойства

White Crystalline Solid

Определение

ChEBI: A sulfonamide consisting of pyrimidine having methoxy substituents at the 5- and 6-positions and a 4-aminobenzenesulfonamido group at the 4-position. In combination with the antiprotozoal pyrimethamine (CHEBI:8673) it is used as an antimalarial.

Антимикробная активность

Its antibacterial activity is relatively poor. Used alone it has a slow and uncertain effect against malaria parasites. Resistance of malaria parasites to the combination with pyrimethamine is common in many endemic areas.

Фармацевтические приложения

An ultra-long-acting sulfonamide. It is no longer prescribed alone, but is used in combination with pyrimethamine as the antimalarial agent Fansidar. It is poorly soluble in water.

Фармаколо?гия

In terms of antibacterial action, this drug is analogous to other sulfanilamides; however, it possesses very prolonged action. Its half-life is from 120 to 200 h. Sulfadoxine is used for infectious diseases caused by microorganisms that are sensitive to the sulfanilamide drugs, such as infections of respiratory organs, gastric and urinary tracts; purulent infections of various localization, osteomyelitis, sinusitis, and other infections. It is used in combination with antimalarial drugs. Synonyms of this drug are sulfarmethoxine, fanasil, and fansidar.

Фармакокине?тика

Oral absorption ：Extensive
C_max 500 mg oral： c. 60 mg/L after 3–4 h
Plasma half-life：c.6 days
Volume of distribution：0.13 L/kg
Plasma protein binding：94%
The extremely long half-life allows administration at weekly intervals. The acetyl metabolite has a similarly long half-life, but sulfadoxine is less extensively metabolized than many other sulfonamides.

Клиническое использование

Sulfadoxine is used only in combination with pyrimethamine.

Побочные эффекты

Side effects are those common to the group. There have been many reports of Stevens–Johnson syndrome following its use and the combination with pyrimethamine is no longer recommended for the prophylaxis of malaria.