Disposition of intravenous amiodarone in subjects with normal and impaired renal function.
In a study designed to determine the influence of renal dysfunction on the disposition of amiodarone and its metabolite, desethylamiodarone (DEA), 30 subjects received a single 5 mg/kg intravenous dose of amiodarone over 15 minutes. Of the 30, 11 had normal renal function (group I; mean +/- SD glomerular filtration rate [GFR] = 118 +/- 20 mL/min/1.73 m2), 9 had renal impairment (group II; GFR = 23 +/- 10 mL/min/1.73 m2), and 10 were long-term hemodialysis patients (group III; 4 of these patients were studied during dialysis). Total and free concentrations of amiodarone and DEA were measured by high-performance liquid chromatography. There were no significant differences between the three groups in mean systemic clearance, steady state volume of distribution, or mean residence time of amiodarone. However, the area under the concentration-time curve (AUC) for amiodarone was significantly higher in group I than in group II, and this finding was related to total body weight. Free fraction was similar in groups I and III. The disposition of amiodarone and its metabolite DEA was similar in patients with normal renal function, moderate renal dysfunction, and end-stage renal disease. Thus, dosage adjustment in patients with renal impairment is not necessary based on this pharmacokinetic analysis.
Ujhelyi
M R
MR
Department of Pharmacy Services, Hartford Hospital, Connecticut, USA.
Klamerus
K J
KJ
Vadiei
K
K
O'Rangers
E
E
Izard
M
M
Neefe
D L
DL
Zimmerman
J J
JJ
Chow
M S
MS
D000328:Adult; D000368:Aged; D000638:Amiodarone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics*; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007262:Infusions, Intravenous; D007668:Kidney / Q000378:metabolism*; D007676:Kidney Failure, Chronic / Q000097:blood / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012016:Reference Values; D006435:Renal Dialysis
D000889:Anti-Arrhythmia Agents; C036116:desethylamiodarone; D000638:Amiodarone