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Probenecid + amoxicillin is a combination of a uricosuric agent and a broad-spectrum beta-lactam antibiotic. Amoxicillin acts by inhibiting bacterial cell wall synthesis through binding to penicillin-binding proteins (PBPs). Probenecid is a renal tubular secretion inhibitor that targets organic anion transporters (OAT1 and OAT3). By blocking the renal excretion of amoxicillin, probenecid increases and sustains its plasma concentrations, thereby potentially improving pharmacokinetic/pharmacodynamic (PK/PD) target attainment. This combination is being investigated by Assistance Publique – Hôpitaux de Paris (AP-HP) in the Phase 3 AMPHORE trial for the treatment of osteoarticular infections, such as osteomyelitis and prosthetic joint infections, where high-dose therapy is required to ensure adequate bone penetration.
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