| Autor: |
D F, Kehrer, A, Sparreboom, J, Verweij, P, de Bruijn, C A, Nierop, J, van de Schraaf, E J, Ruijgrok, M J, de Jonge |
| Rok vydání: |
2001 |
| Předmět: |
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| Zdroj: |
Clinical cancer research : an official journal of the American Association for Cancer Research. 7(5) |
| ISSN: |
1078-0432 |
| Popis: |
This study was designed to evaluate irinotecan (CPT-11) disposition and pharmacodynamics in the presence and absence of the broad-spectrum antibiotic neomycin. Seven evaluable cancer patients experiencing diarrhea gradedor =2 after receiving CPT-11 alone (350 mg/m(2) i.v. once every 3 weeks) received the same dose combined with oral neomycin at 1000 mg three times per day (days -2 to 5) in the second course. Neomycin had no effect on the systemic exposure of CPT-11 and its major metabolites (Por = 0.22). However, it changed fecal beta-glucuronidase activity from 7.03 +/- 1.76 microg/h/mg (phenolphthalein assay) to undetectable levels and decreased fecal concentrations of the pharmacologically active metabolite SN-38. Although neomycin had no significant effect on hematological toxicity (P0.05), diarrhea ameliorated in six of seven patients (P = 0.033). Our findings indicate that bacterial beta-glucuronidase plays a crucial role in CPT-11-induced diarrhea without affecting enterocycling and systemic SN-38 levels. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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