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Comparative Acute Toxicity of Four Drugs

Nathaniel M. Nord

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Abstract

Of the complex aminosugar antibiotics, streptomycin-dihydrostreptomycin, neomycin, kanamycin, and gentamicin have attained to some degree of clinical application. Kanamycin and gentamicin are reported to rival neomycin in antibacterial potency,1without partaking so generously of its toxic properties. However, careful comparison of these agents, taking into account the critical differences in molecular weight, apparently has not been carried out. This report presents the results of side-byside comparisons of equimolar quantities of neomycin, kanamycin, gentamicin, and dihydrostreptomycin with regard to (1) toxicity for bacteria, ie, in vitro antibacterial activity against 246 clinical isolates of gramnegative bacilli; and (2) toxicity for mammalian cells, ie, acute, lethal toxicity to Swiss-Webster albino mice on injection intravenously, intraperitoneally, or intramuscularly. These experiments were concerned with acute toxicity. Consequently, the known, late-appearing, differences in otovestibular toxicity of streptomycin-dihydrostreptomycin2were not relevant. Dihydrostreptomycin, as a chemical derivative of streptomycin, is available in higher purity than is

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Of the complex aminosugar antibiotics, streptomycin-dihydrostreptomycin, neomycin, kanamycin, and gentamicin have attained to some degree of clinical application. Kanamycin and gentamicin are reported to rival neomycin in antibacterial potency,1without partaking so generously of its toxic properties. However, careful comparison of these agents, taking into account the critical differences in molecular weight, apparently has not been carried out. This report presents the results of side-byside comparisons of equimolar quantities of neomycin, kanamycin, gentamicin, and dihydrostreptomycin with regard to (1) toxicity for bacteria, ie, in vitro antibacterial activity against 246 clinical isolates of gramnegative bacilli; and (2) toxicity for mammalian cells, ie, acute, lethal toxicity to Swiss-Webster albino mice on injection intravenously, intraperitoneally, or intramuscularly. These experiments were concerned with acute toxicity. Consequently, the known, late-appearing, differences in otovestibular toxicity of streptomycin-dihydrostreptomycin2were not relevant. Dihydrostreptomycin, as a chemical derivative of streptomycin, is available in higher purity than is

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Available abstract

Of the complex aminosugar antibiotics, streptomycin-dihydrostreptomycin, neomycin, kanamycin, and gentamicin have attained to some degree of clinical application. Kanamycin and gentamicin are reported to rival neomycin in antibacterial potency,1without partaking so generously of its toxic properties. However, careful comparison of these agents, taking into account the critical differences in molecular weight, apparently has not been carried out. This report presents the results of side-byside comparisons of equimolar quantities of neomycin, kanamycin, gentamicin, and dihydrostreptomycin with regard to (1) toxicity for bacteria, ie, in vitro antibacterial activity against 246 clinical isolates of gramnegative bacilli; and (2) toxicity for mammalian cells, ie, acute, lethal toxicity to Swiss-Webster albino mice on injection intravenously, intraperitoneally, or intramuscularly. These experiments were concerned with acute toxicity. Consequently, the known, late-appearing, differences in otovestibular toxicity of streptomycin-dihydrostreptomycin2were not relevant. Dihydrostreptomycin, as a chemical derivative of streptomycin, is available in higher purity than is

Key concepts: Dihydrostreptomycin, Neomycin, Streptomycin, Gentamicin, Kanamycin, Toxicity, Aminoglycoside, Pharmacology

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