Comparative Fecal Pharmacokinetics of Vancomycin Delivered by Gastro-Resistant Capsules and Oral Solution

Background : Clostridioides difficile infection (CDI) is a leading cause of healthcare-associated diarrhea, driven by antibiotic-induced dysbiosis and toxin production. Oral vancomycin is the recommended first-line therapy; however, the conventional formulation is acid-labile and may undergo gastric degradation, potentially affecting colonic drug delivery. Gastro-resistant formulations may improve targeted intestinal release and reduce interindividual variability in drug exposure. Objectives : To compare fecal vancomycin exposure and variability between a gastro-resistant capsule formulation and conventional oral vancomycin administered as an aqueous solution in healthy volunteers. Methods : This prospective, Phase 1 experimental study comprised laboratory and clinical components. Vancomycin stability across pH conditions was assessed, and a high-performance liquid chromatography (HPLC) method for fecal quantification was developed and validated. Ten healthy adults received vancomycin 125 mg every 6 hours for 48 hours, either as gastro-resistant capsules (VanCGR, n=5) or conventional oral solution (VanAD, n=5). Fecal samples were collected after dosing and analyzed for vancomycin concentration. Statistical analyses were primarily descriptive, with comparisons performed using appropriate parametric or non-parametric tests. Results : The HPLC method demonstrated excellent selectivity, linearity (r² ≥0.98), precision, accuracy, and stability. Both formulations achieved fecal vancomycin concentrations far exceeding the minimum inhibitory concentration for C. difficile . Mean fecal concentrations were higher in the VanAD group (4,446.64 µg/g) compared with the VanCGR group (2,784.27 µg/g). However, VanCGR demonstrated lower interindividual variability and a more homogeneous exposure profile. Conclusions : Gastro-resistant vancomycin capsules achieved therapeutically adequate fecal concentrations with reduced variability compared with conventional oral solution. These findings support gastro-resistant delivery as a promising strategy to optimize colonic vancomycin exposure and warrant further evaluation in randomized clinical trials involving patients with active CDI.