Pharmacokinetics of SUN 1165, a new antiarrhythmic agent, in renal dysfunction.
The pharmacokinetics of a new Class I antiarrhythmic agent, SUN 1165, has been studied in 32 patients with varying degrees of renal impairment following a single oral dose of 50 mg. The apparent volume of distribution at steady state was 1.48 l.kg-1, the absorption rate constant was 2.2 h-1, and plasma protein binding was 26.8% in subjects with normal renal function. These variables were not altered with renal impairment. More than 60% of SUN 1165 given orally was excreted unchanged via the kidney, both by tubular secretion and glomerular filtration. The elimination rate constant, the apparent total body clearance and the apparent renal clearance were linearly correlated with the endogenous creatinine clearance. The half-time of elimination was 3.4 h in normal subjects and it was prolonged to 23.7 h in severe renal failure (creatinine clearance below 20 ml.min-1.1.48 m-2). Dosage adjustment of SUN 1165 is necessary in renal failure.
Takabatake
T
T
First Department of Internal Medicine, School of Medicine, Kanazawa University, Japan.
Ohta
H
H
Yamamoto
Y
Y
Ishida
Y
Y
Hara
H
H
Ushiogi
Y
Y
Nakamura
S
S
Hashimoto
N
N
Sasaki
T
T
Satoh
S
S
D058186:Acute Kidney Injury / Q000378:metabolism*; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000889:Anti-Arrhythmia Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D003404:Creatinine / Q000378:metabolism; D005260:Female; D006207:Half-Life; D006801:Humans; D008012:Lidocaine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D008297:Male; D008875:Middle Aged
D000889:Anti-Arrhythmia Agents; D008012:Lidocaine; C042288:pilsicainide; D003404:Creatinine