[Immunological properties of S-1090, cefmatilen hydrochloride hydrate].
S-1090, a cefmatilen hydrochloride hydrate, is being developed as a cephalosporin antibiotic for oral use. Immunogenicity, hypersensitivity-eliciting antigenicity and immunological cross-reactivity with other antibiotics were evaluated by active systemic anaphylaxis (ASA) test, passive cutaneous anaphylaxis (PCA) test and enzyme-linked immunosorbent assay (ELISA) using guinea pigs and mice/rats. In addition, in vitro direct Coombs' test was also performed to examine the possibility of hemolytic anemia in clinical use. Immunogenicity of S-1090 was not observed in guinea pigs after repeated immunization with S-1090 by ASA or PCA tests. Even in ELISA, only weak antibody production against S-1090 was found in some guinea pigs from the intraperitoneal groups showing the antibody titers only 10(1) to 10(2). When the sera collected from C3H/He mice and C57BL/6J mice immunized with S-1090 were tested for immunogenicity, rat PCA was elicited in a C3H/He mouse serum by S-1090 and antibodies against S-1090 were detected in a C57BL/6J mouse serum by ELISA. When adjuvant was used in mice and guinea pigs, the production of antibody against S-1090 was less frequent in comparison with other antibiotics such as cefmetazole (CMZ) and cefotiam (CTM). When hypersensitivity-eliciting antigenicity of S-1090 was examined using S-1090 as an eliciting antigen in ASA and PCA tests, positive ASA and PCA were observed in guinea pigs and positive PCA in a C3H/He mouse. Hypersensitivity-eliciting antigenicity was also observed in other reference antibiotics, i.e. cephalothin (CET), CMZ and CTM. Immunological cross-reactivity among S-1090, penicillin G (PCG), CET, CMZ and CTM was tested by ASA and PCA tests. S-1090 was found to immunologically cross-react only with CET in guinea pigs. In the present study, immunological cross-reactivities were also noted between PCG and CET, PCG and CMZ, PCG and CTM, and between CET and CMZ. In in vitro direct Coombs' test using human red blood cells, S-1090.Na, PCG and CET gave positive reactions at the final concentrations of 40 mg/mL, 20 to 40 mg/mL and 2.5 to 10 mg/mL, respectively.
Takeuchi
M
M
Developmental Research Laboratories, Shionogi & Co., Ltd., 3-1-1 Futaba-cho, Toyonaka, Osaka 561-0825, Japan.
Harada
M
M
Nagata
M
M
Watanabe
A
A
Nakamura
K
K
D000818:Animals; D000941:Antigens / Q000276:immunology*; D015311:Cefmetazole / Q000276:immunology; D015310:Cefotiam / Q000276:immunology; D002511:Cephalosporins / Q000276:immunology*; D002512:Cephalothin / Q000276:immunology; D003298:Coombs Test; D003429:Cross Reactions; D004342:Drug Hypersensitivity / Q000209:etiology*; D005260:Female; D006168:Guinea Pigs; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D010323:Passive Cutaneous Anaphylaxis; D010400:Penicillin G / Q000276:immunology
D000941:Antigens; D002511:Cephalosporins; D015311:Cefmetazole; D015310:Cefotiam; D010400:Penicillin G; D002512:Cephalothin; C419864:cefmatilen