Screening adsorbents for the prevention of drug-induced intestinal dysbiosis at pre-formulation stage: case example activated charcoal

Objectives Develop a biorelevant in vitro methodology to screen adsorbents for their safety and for their efficacy to remove unabsorbed drugs from the colonic lumen using activated charcoal (AC) as a model adsorbent; Evaluate AC’s usefulness in preventing drug-induced intestinal dysbiosis based on in vitro data. Methods Published clinical data with AC and moxifloxacin were used to evaluate biorelevance of the in vitro methodology. In vitro data with four drugs were used to evaluate the usefulness of AC in preventing drug-induced intestinal dysbiosis. Key findings In line with human data, in vitro data indicated that AC has no impact on osmolality and bacterial enzyme activity, and that complete removal of moxifloxacin accumulating in the colon after daily dosing requires the dispersion of >7 g Filtercarb Pharma-A to the colonic lumen. In vitro data with rosuvastatin, azithromycin, and metformin indicated that complete removal after daily dosing requires the dispersion of >3 g, ≈25 g, and >45 g Filtercarb Pharma-A, respectively, to the colonic lumen. Conclusions An in vitro methodology to screen adsorbents for their safety and for their efficacy in removing unabsorbed drugs from the colonic lumen was developed. The effectiveness of AC may be limited by the size and the performance variability of the colon-targeting product.