Oseltamivir probenecid, interaction

No formal drug interaction studies of oseltamivir have been performed. Oseltamivir and its carboxylate metabolite do not interact with the cytochrome P450 system. Although probenecid decreases the elimination of oseltamivir, dosage adjustment is not required during coadministration of these drugs because of oseltamivir s margin of safety. Oseltamivir does not interfere with antibody production in response to the influenza vaccine. 

Probenecid has been reported to inhibit renal elimination of many drugs acyclovir (325,326), allopurinol (327), bumetanide (328), cephalosporins (329-334), cidofovir (335), ciprofloxacin (336), famotidine (337), fexofenadine (338), furosemide (339), and oseltamivir (Ro 64-0802) (340). Recent studies have elucidated that probenecid is a potent inhibitor of renal organic anion transporters (OAT1 and OAT3) with the Ki values lower than the unbound plasma concentration of probenecid, indicating the interaction with probenecid includes inhibition of the basolateral uptake process mediated by OAT1 and/or OAT3. 

Probenecid inhibits the renal secretion of the active metabolite of oseltamivir and marked raises its plasma levels, but this is not clinically relevant because of the wide safety margin of oseltamivir. There was no pharmacokinetic interaction between amoxicillin and oseltamivir, and cimetidine did not alter oseltamivir pharmacokinetics. 

Probenecid markedly increased the AUC of the active metabolite of oseltamivir, but because of the large safety margin of oseltamivir, this increase is not considered to be clinically relevant. " Oseltamivir did not alter amoxicillin pharmacokinetics, and is therefore unlikely to interact with other renally secreted organic acids. Other drugs that are involved in the active anionic tubular secretion mechanism are also unlikely to interact. Cimetidine does not interact with oseltamivir, and other drugs that are inhibitors of the renal cationic secretion transport process are unlikely to interact. ... 

Drug-drug interactions Probenecid In a three-arm, open study 48 healthy volunteers were randomized to oral oseltamivir 75 mg/ day, oseltamivir 75 mg every 48 hours -I- probenecid 500 mg qds, or oseltamivir 75 mg every 48 hours + probenecid 500 mg bd for 15 days. Probenecid reduced the systemic availability of oseltamivir by about 30% and the steady-state apparent oral clearance by about 25% [264 ]. The authors noted that alternate-day dosing of oseltamivir plus probenecid four times a day achieved trough... 

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