AIMS: To assess the effects of dronedarone on renal function and tubular cation handling. METHODS: Twelve healthy males were enrolled in a randomized, cross-over, placebo-controlled, double-blind study. They received 400 mg dronedarone or placebo twice daily for 7 days. Baseline and on-treatment renal function tests were performed under strict standardization of intakes, by assessing creatinine, sinistrin, para-amino-hippurate (PAH) and N-methylnicotinamide (NMN) CLs, and electrolyte excretion. RESULTS: Compared with placebo, dronedarone significantly decreased renal creatinine CL (mean 138-119 ml min(-1) after dronedarone vs. 142-149 ml min(-1) after placebo) and NMN CL (448-368 ml min(-1)vs. 435-430 ml min(-1)), but did not alter renal sinistrin CL, PAH CL and other renal parameters. CONCLUSIONS: Dronedarone reduces renal creatinine and NMN clearance by about 18%, without evidence of an effect on GFR, renal plasma flow or electrolyte exchanges. This suggests a specific partial inhibition of tubular organic cation transporters (OCT). A limited increase in serum creatinine is therefore expected with dronedarone treatment, but does not mean there is a decline in renal function.