An assessment of antigenic potential of beta-lactam antibiotics, low molecular weight drugs, using guinea pig models.
Allergic reactions are among the common adverse effects in humans. However, it is widely assumed that there are practically no reliable animal models for preclinical tests of low-molecular weight drugs that are available to predict such reactions. This study was designed to compare the detecting ability of test methods for antigenic potential of eight beta-lactam antibiotics with which allergic outcome has been reported in humans. The tests included active systemic anaphylaxis (ASA), delayed type skin reaction (DSR), maximization test (GPMT) in guinea pigs sensitized with antibiotics emulsified with Freund's complete adjuvant, passive cutaneous anaphylaxis (PCA) and enzyme-linked immunosorbent assay (ELISA) as serological tests. PCA and ELISA though using protein-conjugates as detecting antigens, especially ELISA, showed positive reactions with relatively high incidence. On the other hand, GPMT was the most sensitive method to detect antigenic potential of antibiotics despite the use of antibiotics alone for sensitizing and challenging phases. It is suggested that GPMT can be considered the most reliable method in preclinical testing.
Hattori
H
H
Drug Safety Research Laboratory, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
Yamaguchi
F
F
Wagai
N
N
Kato
M
M
Nomura
M
M
D000707:Anaphylaxis; D000818:Animals; D000900:Anti-Bacterial Agents / Q000276:immunology*; D000941:Antigens; D015281:Cefmenoxime / Q000276:immunology; D015311:Cefmetazole / Q000276:immunology; D002442:Ceftazidime / Q000276:immunology; D002444:Cefuroxime / Q000276:immunology; D002511:Cephalosporins / Q000276:immunology; D002512:Cephalothin / Q000276:immunology; D004342:Drug Hypersensitivity; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006168:Guinea Pigs; D006968:Hypersensitivity, Delayed; D007428:Intradermal Tests; D010323:Passive Cutaneous Anaphylaxis; D010878:Piperacillin / Q000276:immunology
D000900:Anti-Bacterial Agents; D000941:Antigens; D002511:Cephalosporins; D015311:Cefmetazole; D002442:Ceftazidime; D015281:Cefmenoxime; D002444:Cefuroxime; D002512:Cephalothin; C045693:flomoxef; D010878:Piperacillin