Modeling the effect of DAV132, a novel colon-targeted adsorbent, on fecal concentrations of moxifloxacin and gut microbiota diversity in healthy volunteers.

Modeling the effect of DAV132, a novel colon-targeted adsorbent, on fecal concentrations of moxifloxacin and gut microbiota diversity in healthy volunteers. Clin Pharmacol Ther. 2020 Jul 02;: Authors: Guk J, Guedj J, Burdet C, Andremont A, de Gunzburg J, Ducher A, Mentré F Abstract To prevent antibiotic-induced perturbations on gut microbiota, DAV132, a novel colon-targeted adsorbent, which sequesters antibiotic residues in the lower gastrointestinal tract was developed. We built an integrated pharmacological model of how DAV132 reduces fecal free moxifloxacin (MXF) and preserves gut microbiota. We used plasma and fecal free MXF concentrations, and Shannon diversity index from 16S rRNA gene metagenomics analysis of fecal microbiota, of 143 healthy volunteers assigned randomly to receive MXF only, or with ten DAV132 dose regimens, or to a control group. We modeled reduced fecal MXF concentrations using a transit model for DAV132 kinetics and a Michaelis-Menten model with an effect of the amount of activated charcoal on adsorption efficacy. Changes in MXF-induced perturbations on gut microbiota diversity were then quantified through a turn-over model with the Emax model. With the developed model, the efficiency of pharmacokinetic antagonism and its consequences on gut microbiota diversity were quantified. PMID: 32617960 [PubMed - as supplied by publisher]
Source: Clinical Pharmacology and Therapeutics - Category: Drugs & Pharmacology Authors: Tags: Clin Pharmacol Ther Source Type: research