Modulation of irinotecan-induced diarrhea by cotreatment with neomycin in cancer patients
2001
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 ≥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 ≥ 0.22). However, it changed fecal β-glucuronidase activity from 7.03 ± 1.76 μg/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 β-glucuronidase plays a crucial role in CPT-11-induced diarrhea without affecting enterocycling and systemic SN-38 levels.
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