Treatment of pneumonia with sulfidine during the Great Patriotic War, 1941 – 1945

Abstract

Synthesis, manufacturing and clinical trials of sulfonamides during the Great Patriotic War is a glorious page of Russian pharmaceutical industry and clinical medicine. Sulfidine, the active sulfonamide, was synthesized in 1937 under the stewardship of I.Y.Postovsky. Sulfidine manufacturing was organized in 1942. Pharmacokinetics and pharmacodynamics of sulfidine were investigated in a number of studies of the time. Blood concentration of sulfidine reached 0.88 – 3.1 0 mg/dL within 4 h after a single oral dose of 1 – 3 g. The peak concentration was observed in 8 – 12 h and was held at this level within 8 – 16 h. To achieve clinical effect, researchers recommended maintaining sulfidine concentration ≥ 3 – 4 mg/dL during 3 or 4 days. The oral administration of sulfidine was associated with gastrointestinal adverse events in 31% of patients; skin rash in 7% of patients, and polyneuritis in one patient. Therefore, Soviet investigators developed intravenous formulation of sulfidine. Pneumonia treatment with i.v. sulfidine required 0.75 – 3.0 g of the drug compared to 24 g of oral formulation. I.v. sulfidine caused less adverse events and similar clinical effect compared to the oral route of administration. Sulfidine treatment of pneumonia led to outstanding results including dramatically decreased mortality from 30% to 4 – 6%. A valuable experience of development and implementation of antibacterial drugs during the Great Patriotic War could be used for revival of the Russian national pharmaceutical industry.