Reactions Between Penicillins and Pharmaceutical Adjuvants

An additional source of preformed antigenic penicilloyl-specific substances in penicillin preparations may be penicilloyl-carbohydrate conjugates. 

In 1962 Siegel (1962) observed that benzylpenicillin incubated with the additive carboxymethylcellulose was capable of producing a wheal and flare reaction in sensitive patients. Later, Schneider et al. (1971 a) have shown that the antigenic product produced in the reaction between penicillin and the additive is a penicilloy-lated carboxymethylcellulose conjugate. 

Several therapeutically used penicillin preparations contain carbohydrates. Thus, penicillins are commonly infused in glucose or fructose solutions, sucrose is a common ingredient of penicillin syrups and benzylpenicillin procaine suspensions may contain carboxymethylcellulose as an additive. Because of the antigenic and potentially allergenic effect of penicilloyl-carbohydrate conjugates, their presence in penicillin preparations must be avoided. Information about the kinetics of reaction of penicillins with carbohydrate and factors affecting the reaction rate have recently been reported. 

Bundgaard and Larsen (1978 a) have studied the kinetics and mechanism of the sucrose-accelerated degradation of benzylpenicillin and a number of semisyn- 

The formation of penicilloyl esters can, for all penicillins, be greatly depressed or avoided by adjusting the pH of penicillin solutions containing the hydroxy com- 

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