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Modeling the Effect of DAV132, a Novel Colon‐Targeted Adsorbent, on Fecal Concentrations of Moxifloxacin and Gut Microbiota Diversity in Healthy Volunteers
Author(s) -
Guk Jinju,
Guedj Jérémie,
Burdet Charles,
Andremont Antoine,
Gunzburg Jean,
Ducher Annie,
Mentré France
Publication year - 2021
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt.1977
Subject(s) - moxifloxacin , feces , gut flora , antibiotics , pharmacokinetics , metagenomics , biology , microbiology and biotechnology , pharmacology , immunology , biochemistry , gene
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 and preserves gut microbiota. We used plasma and fecal free moxifloxacin concentrations, and Shannon diversity index from 16S ribosomal RNA gene metagenomics analysis of fecal microbiota, of 143 healthy volunteers assigned randomly to receive moxifloxacin only, or with 10 DAV132 dose regimens, or to a control group. We modeled reduced fecal moxifloxacin 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 moxifloxacin‐induced perturbations on gut microbiota diversity were then quantified through a turnover model with the Emax model. With the developed model, the efficiency of pharmacokinetic antagonism and its consequences on gut microbiota diversity were quantified.