Ampicillin Polymers as Elicitors of Passive Cutaneous Anaphylaxis

Abstract

The ability of ampicillin polymers to elicit passive cutaneous anaphylaxis (PCA) reactions in guinea pigs was analyzed. Mediating antibodies were raised in rabbits against a crude preparation of 6-aminopenicillanic acid (6-APA). It was found that large ampicillin polymers were potent elicitors, 1,000-fold better than benzylpenicillin polymers. Small polymers in high concentrations did not elicit PCA reactions but inhibited the activity of the larger polymers. This inhibition was more pronounced than that of ampicillin monomer. High molecular weight of ampicillin polymer in the amount of 0.1% in an ampicillin solution manifested its PCA activity. The tendency of ampicillin to polymerize, particularly when kept in solution, makes this observation worth considering. The PCA reactions described were penicilloyl-specific as verified by immunosorbent experiments.

Antigenicity of Beta-Lactam Antibiotic Preparations: Production of IgE Antibodies to Beta-Lactam Antibiotic and Their Cross-Reaction Within the Antibiotic Group

“…The other is the presence of the intrinsically antigenic high molecular weight im purities in the pharmaceutical preparations. These impurities were classified into two categories: the pro teinaceous impurities derived from the fermentation process or from amydase used for the production pro cess [5,9,24,28], and the homopolymeric impurities born during the production or storage process espe cially in a solution [2,3,15,24,28,29].…”

“…While in the animal experiments an ability of the polymers to induce antibodies have not always been confirmed [4,15,18], their ability to elicit anaphylac tic reactions have been convincingly demonstrated [3,15,25]. However, the polymers used as the immuno gens or the elicitors in these experiments were those isolated from the solution aged to produce the poly mers artificially [2,3,25].…”

Thermostability Comparison of Two Solid States of Cefpiramide

“…At the end of the accelerated and stress studies, XRPD was performed to evaluate the structural stability of the different forms, and high molecular mass polymers were also determined since β-lactam antibiotic polymerization is likely to occur under severe conditions (e.g. high temperature) and might cause anaphylaxis in clinical therapy [20][21][22][23]. …”

“…It is of common knowledge that the polymers of β-lactam antibiotics have great impact on the safety of β-lactam antibiotics since they might induce anaphylaxis in clinical therapy [20][21][22][23]. Therefore, at the end of the stability studies, high molecular mass polymers in the samples being examined were analyzed by a validated SEC method (see The Method for High Molecular Mass Polymers) and results are shown in Table 4.…”

Antigens in Penicillin Allergy

“…The pcnicilloyl-protein conjugates used for raising antibodies or as reference in the RIA were recently described [5], A reteníate of a crude 6-aminopenicillanic acid was utilized to raise the antibodies used in the PCA experiments [2].…”