(A) CPT-11 (irinotecan) produced delayed diarrhea in 25%, 60%, and 100% of mice in 8, 9, and 10 days, respectively. Oral delivery of Inhibitor R1, a 1.9-μM inhibitor of E. coli β-glucuronidase, reduces the number of mice that experience diarrhea at days 9 and 10 to 40% and 60%, respectively, but is less effective than Inhibitor 1, a 0.16-μM inhibitor, on which it was based. N = 9 mice per group.
(B) The circulating plasma levels of CPT-11, its active metabolite SN-38, or its inactive glucuronide conjugate SN-38-G are unaffected by the oral delivery of the microbial β-glucuronidase Inhibitor 1 (Inh1).