Targeted adsorption of molecules in the colon with the novel adsorbent‐based Medicinal Product, DAV132: A proof of concept study in healthy subjects

Abstract

During antibiotic treatments, active residuals reaching the colon profoundly affect the bacterial flora resulting in the emergence of resistance. To prevent these effects, we developed an enteric-coated formulated activated-charcoal based product, DAV132, meant to deliver its adsorbent to the ileum and neutralize antibiotic residues in the proximal colon. In a randomized, control, crossover study, the plasma pharmacokinetics of the probe drugs amoxicillin (500 mg) absorbed in the proximal intestine, and sulfapyridine (25 mg) metabolized from sulfasalazine in the cecum and rapidly absorbed, were compared after a single administration in 18 healthy subjects who had received DAV132, uncoated formulated activated charcoal (FAC) or water 16 and 8 hours before, concomitantly with the probe drugs, and 8 hours thereafter. The AUC0-96 h of amoxicillin was reduced by more than 70% when it was taken with FAC, but bioequivalent when it was taken with water or DAV132. By contrast, the AUC0-96 h of sulfapyridine was reduced by more than 90% when administered with either FAC or DAV132 in comparison with water. The results show that DAV132 can selectively adsorb drug compounds in the proximal colon, without interfering with drug absorption in the proximal small intestine, thereby constituting a proof of concept that DAV132 actually functions in humans.

Impact of Fluoroquinolones on Human Microbiota. Focus on the Emergence of Antibiotic Resistance

“…in a mouse model of gut colonization [85]. In human volunteers, these products have recently shown that they can selectively adsorb drug compounds in the proximal colon, without interfering with drug absorption in the proximal small intestine [86]. Co-administration of ciprofloxacin and activated charcoal inserted in zinc balls (which release the coal only in the colon) also showed a significant decrease in fecal concentrations of ciprofloxacin in rats and no effect on PK/PD plasma ciprofloxacin parameters [87].…”

“…Yet, before this occurs, we hope to see more successful ways of limiting the impact of antibiotics on microbiota, and not only concerning FQ, such as charcoal-based coating techniques to limit the impact of antibiotics in the proximal colon. The proof of concept has been made and clinical studies have recently begun [85,86]. Closer down the line, FMT may also be an alternative treatment for subjects colonized with multi resistant organisms and suffering recurring infections.…”

New and emerging therapies for Clostridium difficile infection

“…43 This adsorbent product irreversibly captures antibiotics in the intestine whilst hopefully avoiding interruption of antibiotic absorption. DAV132 has been examined in a proof-of-concept study involving 18 healthy subjects.…”

“…In vitro human gut model and in vivo hamster models also have positive findings but clinical efficacy data are awaited. 43 …”

Pectin beads loaded with chitosan–iron microspheres for specific colonic adsorption of ciprofloxacin

“…Another study has demonstrated the potentiality of non-enzymatic intra-intestinal inactivation of residual ciprofloxacin by colon-targeted zinc-pectinate beads loaded with activated charcoal [13,14]. This approach has recently been applied with success in a phase I clinical trial [15]. This system is however not selective to the antibiotics and nonspecific adsorption of other molecules can occur interfering with major physiological processes.…”