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• W2024956881 abstract "Variations in the treatment of polymyxin B and polymyxin E (colistin) with formaldehyde and sodium bisulphite produce sulphomethyl derivatives which differ quantitatively in acute toxicity and in antibacterial activities in vitro and in vivo. The acute intravenous LD50 values of some sixty samples of these derivatives range from six- to more than eighty-fold those of the parent antibiotics; the in vitro antibacterial activities range from 2 to 12% and the in vivo activities from 20 to 50% of those of the parent antibiotics, with the most toxic derivatives showing the highest activities. When short and prolonged incubation methods are used, assays of the derivatives in solutions of different ages and of blood collected from man and dog after intramuscular injection, show that the antibacterial activities of these sulphomethyl derivatives depend on reversion to the unsubstituted form, and that the differences in the activities are due to variations in stability. These conclusions are supported by comparison of these sulphomethyl derivatives with stable acetyl derivatives. The lower in vivo activity is due, at least partly, to the high renal excretion of the substituted form. Electrophoresis shows that the derivatives are composite, the components corresponding to mono- to pentasulphomethyl polymyxin. Pain at the injection site is the most troublesome side-effect of polymyxin therapy, and this is avoided with these derivatives. In rats injected with quantities some twenty-times the usual human dose, the derivatives cause transitory decrease in urinary output and transitory proteinuria. After intramuscular injection of these derivatives into dogs, no antibiotic is detectable in the cerebrospinal fluid and concentrations present in the bile are not significantly different from those after injection of the parent antibiotic. When injected intracisternally into these animals, derivatives are less toxic than the parent compounds. These studies show that acute intravenous toxicity is a useful index of therapeutic efficiency and that derivatives with intravenous LD50 values of about 100 mg/kg are the most satisfactory ones. Because activity depends on reversion to the parent antibiotic, the use of these derivatives for topical application is contraindicated." @default.
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• W2024956881 date "1964-12-01" @default.
• W2024956881 modified "2023-10-14" @default.
• W2024956881 title "SODIUM SULPHOMETHYL DERIVATIVES OF POLYMYXINS" @default.
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• W2024956881 doi "https://doi.org/10.1111/j.1476-5381.1964.tb01610.x" @default.
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