Modulation of irinotecan-induced diarrhea by cotreatment with neomycin in cancer patients
January 2001
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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 graded > or =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 (P > or = 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 (P > 0.05), 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.
- Adult
- Aged
- Humans
- Middle aged
- Research Support, Non-U.S. Gov't
- Adolescent
- Anti-Bacterial Agents/therapeutic use
- Diarrhea/chemically induced/*drug therapy
- Neomycin/*therapeutic use
- Cross-Over Studies
- Antineoplastic Agents, Phytogenic/*adverse effects
- Camptothecin/*adverse effects/analogs & derivatives
- Neoplasms/*complications/drug therapy
- diarrhea
- patient
- -11
- cpt -11
- neomycin
- glucuronidase activity
- course
- cancer
- -38
- plasma
- glucuronidase
- activity
- sn -38
- treatment
- study
- pharmacokinetic
- irinotecan
- sn -38g
- delayed-type diarrhea
- administration
