DRUG-SPECIFIC IMMUNE RESPONSES INDUCED BY IMMUNIZATION WITH DRUGS IN GUINEA PIGS AND MICE
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概要
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In order to develop a system for evaluating the allergenicity of drugs in clinical use, we tested drugs for the ability to induce drug-specific immune responses in guinea pigs and mice. Test drugs were benzylpenicillin, procainamide, hydralazine, isoniazid, α-methyldopa, D-penicillamine, captopril, sulfamethoxazole and 2,4-dinitrochlorobenzene (DNCB), which are known to induce allergic responses in man including hypersensitivity reactions and drug-induced auto-immune responses. Guinea pigs were immunized with an emulsion of complete Freund's adjuvant (CFA) and 25 mg of each drug. Mice were immunized with an emulsion of CFA and 2 mg of each drug or a mixture of aluminum hydroxide gel and 2 mg of each drug. In order to examine drug-specific immune responses, we employed detection of antibodies by enzyme-linked immunosorbent assay (ELISA) and passive cutaneous anaphylaxis tests, active systemic anaphylaxis (ASA) tests and delayed type hypersensitivity (DTH) tests. In guinea pigs, drug-specific antibodies were detected following immunization with benzylpenicillin, procainamide, hydralazine, isoniazid, captopril, sulfamethoxazole or DNCB. Some of these drugs were also positive in DTH tests and/or ASA tests. In mice, however, only DNCB gave positive results. Therefore, our system involving immunization of guinea pigs with CFA emulsion of a drug and detection of drug-specific immune responses is considered to be an effective test method for evaluating drug allergenicity.
- 日本トキシコロジー学会の論文
- 1992-11-25
著者
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SHIONOYA Hiroshi
Department of Drug Safety Research, Eisai Kawashima Research Laboratories, Eisai Co., Ltd.
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Katsutani Naruo
エーザイ
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Katsutani Naruo
Department Of Developmental Safety Assessment Research Eisai Co. Ltd.
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Shionoya H
Department Of Drug Safety Research Eisai Kawashima Research Laboratories Eisai Co. Ltd.
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