Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

DMP 406 is an atypical antipsychotic, antischizophrenic drug, biochemically related to clozapine, which exerts its desired pharmacologic effects through selective antagonism of 5-hydroxytryptamine and dopamine-receptor subtypes. Clozapine therapy is clinically associated with severe granulocytopenia in a small subset of patients. In the course of a 3-month toxicity study in dogs, severe neutropenia, thrombocytopenia, marked myeloid and erythroid left-shifted bone marrow hyperplasia with increased erythrophagocytosis, positive Coombs' tests, and hypergammaglobulinemia occurred in individual females dosed with 30 mg/kg/day of DMP 406. Related but less severe changes were also observed in males. Sera or purified immunoglobulins from affected and control dogs were tested in methylcellulose-based, canine hematopoietic colony-forming unit (CFU) assays with or without DMP 406. Neither size nor number of erythroid or myeloid CFUs differed between cultures containing control or affected dog serum components. Sera from individual affected dogs but not controls resulted in moderate numbers of fibroblast-like CFUs, suggesting DMP 406-associated marrow stromal cell-modifying, serum activities to be present. DMP 406 alone resulted in a concentration-dependent reduction of erythroid and myeloid CFUs with an approximate IC50 of 3.0 microg/mL. Taken together, DMP 406-induced granulocytopenia and bone marrow dyscrasia appear likely to result from both immune-mediated and direct drug-induced myelotoxicity.
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PMID:Atypical antipsychotic-induced neutropenia in dogs. 1007 8

There have only been a few reports about adverse events of methotrexate, vinblastine, adriamycin and cisplatin (MVAC) chemotherapy under supportive care with granulocyte stimulating factor (G-CSF) and 5-hydroxytryptamine 3 receptor (5-HT3R) antagonists. The purpose of this study was to retrospectively review the adverse events of the chemotherapy. We analyzed 59 patients with advanced bladder cancer who received MVAC chemotherapy at Sapporo Medical University hospital from January 1992 to September 2004. The adverse events were evaluated according to the Common Terminology Criteria for Adverse Events version 3.0 (Japanese edition). Thirty-one of the 59 patients (52.6%) received MVAC in the neoadjuvant setting. Two courses of chemotherapy were most frequently used in the neoadjuvant and adjuvant settings, and treatment of metastatic or recurrent lesions. More than 90% of patients experienced hematological adverse events such as some grade of leukocytopenia and neutropenia in each course of the chemotherapy. Grade 3 or 4 neutropenia was seen in 60-75% of patients. Grade 3 or 4 leukopenia and/or neutropenia in the first course of the chemotherapy was associated with patients with impaired renal function (60 mL/min< or = creatinine clearance <80 mL/min). Febrile neutropenia was found in 6 patients (5.0%), including one who died of subsequent septic shock and adult respiratory distress syndrome. Nausea was seen in 70-80% of patients. MVAC chemotherapy for advanced bladder cancer was performed with tolerable adverse events. The current results provide relevant information mainly for those who need 2 courses of chemotherapy in the neoadjuvant or adjuvant setting.
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PMID:Adverse events of MVAC chemotherapy in patients with advanced urothelial cancer of the bladder. 1751 69