Topic
Cefazedone
About: Cefazedone is a research topic. Over the lifetime, 49 publications have been published within this topic receiving 311 citations. The topic is also known as: EMD-30087.
Papers
TL;DR: It is concluded that antibody‐mediated blood cell destruction contributes to all three cephalosporin‐induced cytopenias in the dog.
Abstract: Cephalosporin treatment in man has been associated with a low incidence of hemolytic anemia, thrombocytopenia, and neutropenia; some cases have been shown to be immune-mediated. This triad of blood dyscrasias was also demonstrated in our laboratory in a series of toxicity studies in dogs of two cephalosporin compounds, cefonicid and cefazedone; these studies provided evidence for drug-associated immune hemolytic anemia, based on conventional laboratory tests. To further investigate possible immune mechanisms of the cephalosporin-induced cytopenias, we measured erythrocyte-associated, platelet-associated (PAIgG), and serum antineutrophil IgG over the course of cephalosporin treatment, using highly sensitive 125I-staphylococcal protein A (SPA) assays, as well as the direct antiglobulin test; we compared these findings with the hematologic changes. Intravenous treatment with high doses of cefazedone (540 mg/kg/day, increased to a maximum of 840 mg/kg/day for 4 months or until hematologic effects were evident) resulted in a high incidence of anemia (7/14), thrombocytopenia (11/14), and neutropenia (7/14). Of the affected dogs examined, 6/7 with anemia, 9/9 with thrombocytopenia, and 7/7 with neutropenia showed increased levels of the respective cell-associated antibody, compared with untreated controls. Unaffected dosed animals generally did not show these changes. In 3/3 dogs examined following remission of thrombocytopenia, PAIgG returned to levels comparable with controls; as one of these dogs suffered a relapse, increased PAIgG was again observed. Animals sacrificed during cytopenic episodes showed cytologic and histologic evidence of increased hemophagocytosis. We conclude that antibody-mediated blood cell destruction contributes to all three cephalosporin-induced cytopenias in the dog.
44 citations
TL;DR: The results suggest that the teratogenic effect of cefazedone and cefazolin sodium on zebrafish embryonic development is associated with the structure of MMTD, which should be recommended as a specified impurity and qualified as serious again.
Abstract: 2-mercapto-5-methyl-1,3,4-thiadiazole (MMTD) is the 3’-side chain of cephalosporin including cefazolin sodium (CFZL) and cefazedone (CFZD). It is not only present in finished products as the residual precursor, but also produced through drug degradation. Performing the zebrafish embryo toxicity test, we evaluated the toxicity effects of cefazolin sodium, cefazedone, their synthetic precursors and intermediates. Our results suggest that the teratogenic effect of cefazedone and cefazolin sodium on zebrafish embryonic development is associated with the structure of MMTD. They mainly interfere with the development of tissues and organs derived from embryonic ectoderm and mesoderm. We further consider the rationality of the quality control limit of MMTD (1.0%) in the specification. As the acceptable daily intakes (ADIs) of cefazolin is 10 mg/kg per day [16] and the minimum teratogenic concentration of MMTD is tenfold lower than that of cefazolin sodium, we recommend that the acceptable daily intakes of MMTD should be 1 mg/(kg day). In general, the therapeutic dose of cefazolin sodium is 2–4 g/day. Based upon the calculation of MMTD quality control limits (1.0%), MMTD intake can be 20–40 mg/day, which will be much more than the acceptable daily intake value of 1 mg/(kg day). Thus, MMTD should be recommended as a specified impurity and qualified as serious again.
38 citations
Journal Article•
TL;DR: Care must therefore be taken in the determination of creatinine in samples from patients under treatment with these drugs, the assay methods of choice at present are enzymatic or specific HPLC assays.
Abstract: The new cephalosporin, cefpirome, was investigated for its possible interference in clinical laboratory tests, especially the determination of creatinine. Tests for bilirubin, cholesterol, protein, urea, and uric acid were also studied. A selection of commercially available compounds such as cefoperazone, cefazolin, cefamandole, cefoxitin, latamoxef, ceftriaxon, cefotiam, cephaloridine, cephalotin, cefotaxime, cefazedone and cefuroxime, and cefodizime (a compound under development) were also included in these investigations. Interference was found only with the "Jaffe method" for the determination of creatinine. Pronounced interactions with alkaline picrate were observed with cefpirome, cefoxitin, cephalotin and cephaloridine, whereas the other compounds showed only weak reaction or no reaction at all. The cephalosporins did not interfere in any of the other tests mentioned above. Care must therefore be taken in the determination of creatinine in samples from patients under treatment with these drugs. The assay methods of choice at present are enzymatic or specific HPLC assays.
21 citations
TL;DR: Observations suggest that the hematologic syndrome associated with cephalosporin treatment in the dog has multiple toxicologic mechanisms, which include peripheral cytotoxic effects and bone marrow damage with depressed or ineffective hematopoiesis.
14 citations
TL;DR: It is concluded that the administration of high doses of cefonicid or cefazedone to dogs can induce hematotoxicity similar to the cephalosporin-induced blood dyscrasias described in man and thus provides a useful model for studying the mechanisms of these disorders.
14 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2019 | 1 |
| 2017 | 1 |
| 2015 | 2 |
| 2014 | 5 |
| 2011 | 2 |
| 2010 | 6 |