A pilot study, randomized control trial on effect of oral calcium carbonate to fecal functional levofloxacin concentration in healthy volunteer taking oral levofloxacin

Abstract

Objective: We conducted a pilot randomized control trial (RCT) to study whether oral calcium carbonate (CaCO3) can lower fecal levofloxacin (LVX) concentration and preserve gut microbiota diversity in healthy volunteers. Methods: The healthy volunteers received a 5-day course of once-daily 500 mg LVX oral tablet and were randomly assigned to treatment (6-day course of 1,000 mg CaCO3 oral tablet twice daily) and control group (no CaCO3). The primary outcome was fecal LVX concentration by MIC and high-performance liquid chromatography (HPLC) on day 2 and 5. The secondary outcomes were fecal microbiota diversity Shannon index (H) by 16s rDNA analysis, plasma LVX Cmax by HPLC, and drug adverse events (AEs) in 4 weeks period. Results: Total 20 volunteers were enrolled and randomly assigned to treatment and control group. Mean fecal LVX concentration was higher in treatment than control group, 100.50 (SD=64.88) vs 53.21 (SD =39.57) µg/ml by MIC at day 5 (95% CI 4.912, 89.73; p = 0.0242). No difference in mean fecal LVX concentrations by HPLC, plasma LVX Cmax. Treatment group had significantly declined in H index (p = 0.0019). Only mild AEs included nausea and diarrhea. Conclusion: CaCO3 is significantly related to higher fecal LVX level by MIC but does not significantly affect the LVX Cmax. However, rather than protecting gut microbiota from LVX, CaCO3 may lower gut microbiota diversity in the presence of LVX. Therefore, co-prescription of LVX and CaCO3 might be cautioned even without the concern about the absorption and further research is needed in the future.