Studies on the Stability of Drugs in Biological Media. III. Effect of Cupric Ion on the Stability and Antibacterial Activity of Penicillins in Culture Medium

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The effect of cupric ion on the stability and antibacterial activity of penicillins, benzylpenicillin and 2,6-dimethoxyphenylpenicillin, in phosphate buffer solution and phosphate broth kept at pH 5.0 was investigated. The degradation was found to obey first-order kinetics to produce the corresponding penicillenic acids, though the formation of penicilloic acid analogs have been postulated in other studies. Catalytic and complexing effect of cupric ion on the stability of penicillins was revealed in relatively lower and higher concentrations of the metal ion respectively, where an appreciable difference in the effect was noted between buffer solution and broth. Apparent stability constants for the proposed complex between penicillins and cupric ion were estimated to be log K_<app>=2.65 and 2.91 with benzylpenicillin and 2,6-dimethoxyphenylpenicillin, respectively. The antibacterial activity against Staphylococcus aureus was not apparently affected by the addition of cupric ion, which indicates an apparent lack of correlation between the stability and the activity of the drug in broth. This is presumably because the probable enhancing effect of the metal ion on the cell wall permeability of the penicillins outweighs the other effects investigated.
社団法人日本薬学会の論文
1971-04-25