Systemic pharmacokinetics of rifaximin (RFX) in subjects with shigellosis

Abstract

Background Rifaximin (RFX) is a non-systemic (F <0.4%), gut-selective rifamycin SV antimicrobial agent recently approved for the treatment of travelers' diarrhea. This study was done to evaluate the systemic PK of RFX given to subjects with Shigella flexneri diarrhea. Methods The study was a single-site, open-label PK and safety study of RFX 200 mg given every 8 hours for 9 doses. Subjects were challenged with S. flexneri and subsequently treated with RFX if a standard definition of diarrhea was met. Blood samples were taken for RFX PK with the 3rd and 9th doses of RFX administered under fasting conditions. Results Fifteen subjects were enrolled; 13 developed diarrhea, received RFX and were evaluable for PK and safety. RFX was well tolerated; no significant adverse events were reported. The table below shows the mean (±SD) RFX PK parameters. Mean, dose-normalized parameters from a separate single-dose study in fasted healthy subjects are also shown for the sake of comparison: Conclusions Systemic RFX exposure was low and variable in the subjects with shigellosis. The PK and safety of RFX in patients with diarrhea caused by S. flexneri were comparable to those in healthy volunteers. These results are consistent with previously reported RFX PK (F <0.4%) and safety data. Clinical Pharmacology & Therapeutics (2005) 77, P60–P60; doi: 10.1016/j.clpt.2004.12.118 3rd dose RFX 200 mg 9th dose RFX 200 mg Single dose RFX 200 mg Cmax (ng/mL) 1.63 ± 0.86 1.23 ± 0.52 1.9 AUC0-last (ng*hr/mL) 6.95 ± 5.15 7.83 ± 4.94 9.2 Tmax (hr) 2.77 ± 2.24 2.11 ± 1.58 1.21