Does probenecid increase tigecycline's serum concentration?
Yes, probenecid increases tigecycline's serum concentration by inhibiting its renal and biliary clearance. Tigecycline, a glycylcycline antibiotic, undergoes minimal renal excretion (about 15-20%) and significant biliary/fecal elimination. Probenecid blocks organic anion transporters (OATs) in the kidneys and multidrug resistance-associated proteins (MRPs) in the bile, reducing tigecycline efflux and raising plasma levels by 25-45% in pharmacokinetic studies.[1][2]
How was this interaction discovered?
Clinical trials and in vitro studies identified the effect. A phase 1 study in healthy volunteers showed probenecid (2g daily) increased tigecycline's AUC by 41% and Cmax by 27% without altering half-life significantly. This stems from tigecycline's substrate affinity for OAT1/3 and MRP2, which probenecid competitively inhibits.[1][3]
What does this mean for tigecycline dosing?
No routine dose adjustment is FDA-recommended, but monitor for tigecycline-related toxicities like nausea or elevated liver enzymes if co-administered. The interaction could enhance efficacy against resistant infections but risks overexposure.[2][4]
Are there clinical cases or guidelines on this?
Limited case reports exist; one described successful tigecycline salvage therapy for Acinetobacter with probenecid to boost levels amid renal impairment. Guidelines (e.g., IDSA) note the interaction but advise caution over avoidance.[3][5]
Does this apply to similar drugs or conditions?
Probenecid similarly boosts concentrations of other renally/biliarly cleared antibiotics like cefadroxil or temocillin. In liver disease or cholestasis, the effect amplifies due to tigecycline's hepatobiliary route.[2][6]
[1]: Tigecycline prescribing information, FDA label
[2]: Drug interactions with tigecycline, Clinical Pharmacology & Therapeutics
[3]: Probenecid-tigecycline interaction study, Antimicrob Agents Chemother
[4]: IDSA guidelines on multidrug-resistant infections
[5]: Case report on tigecycline enhancement, J Antimicrob Chemother
[6]: OAT/MRP inhibition review, Pharmacol Rev