Effect of dronedarone on renal function in healthy subjects.
OBJECTIVE
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.
Clinical Pharmacology and Toxicology, University Hospital, Lausanne, Switzerland.
Yvonne
Y
Tschuppert
Thierry
T
Buclin
Laura E
LE
Rothuizen
Laurent A
LA
Decosterd
Jacques
J
Galleyrand
Christine
C
Gaud
Jérôme
J
Biollaz
D000328:Adult; D000638:Amiodarone / Q000031:analogs & derivatives* / Q000494:pharmacology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D000077764:Dronedarone; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism*; D007677:Kidney Function Tests / Q000379:methods; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects / Q000502:physiology
D000077764:Dronedarone; D000638:Amiodarone