The Paris-based biotechnology company Da Volterra has published in the American College of Clinical Pharmacology review, and in collaboration with the University Medicine of Greifswald and the INSERM laboratory UMR 1137 (University Paris Diderot and Hôpital Bichat AP-HP Paris), the results of a clinical proof-of-concept study demonstrating DAV132 delivery in humans. DAV132 is the company most advanced clinical-stage asset.
DAV132 – an adsorbent-based product encapsulated in a specific drug delivery vehicle – is destined to be co-administered with antibiotic treatments to prevent occurrence and recurrence of Clostridium difficile infections (CDI) in at-risk patients. The study demonstrated the site-specific delivery of DAV132, which can adsorb drug compounds such as antibiotic residues in the proximal colon without interfering with drug absorption in the proximal small intestine in human digestive system.
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.
de Gunzburg, J., Ducher, A., Modess, C., Wegner, D., Oswald, S., Dressman, J., Augustin, V., Feger, C., Andremont, A., Weitschies, W. and Siegmund, W. (2015), Targeted adsorption of molecules in the colon with the novel adsorbent-based Medicinal Product, DAV132: A proof of concept study in healthy subjects. Journal of Clinical Pharma, 55: 10–16. doi: 10.1002/jcph.359
Read full article: http://onlinelibrary.wiley.com/doi/10.1002/jcph.359/abstract