title: Long-term plasma levels and dose modulation of alacepril in patients with chronic renal failure.
abstract: Because most angiotensin-converting enzyme inhibitors are excreted into urine, any decrease in renal function increases the plasma levels of these drugs. This study was designed to investigate the appropriate doses of alacepril in patients with chronic renal failure. The total plasma concentration of captopril, an active metabolite of alacepril, was measured in 47 patients with chronic renal failure or normal renal function. Fifteen patients on chronic hemodialysis were also enrolled in this study. In patients treated with 12.5, 25 and 50 mg alacepril, the plasma concentration of captopril was linearly correlated with serum creatinine and creatinine clearance (Ccr). There was an approximately 40% decrease of the plasma captopril concentration after 4 h of hemodialysis. Among patients treated with 25 or 50 mg alacepril for 4.5 years, the plasma concentration of captopril gradually increased along with an increase in serum creatinine (from 2.0 to 5.8, and from 1.9 to 7.1 mg/dL, respectively). Although the plasma concentration of captopril was higher in the 50 mg group, the increase in serum creatinine during this period was not different between the two groups. The plasma aldosterone concentration did not increase during this period. These data suggest that alacepril should be reduced from 50 to 25 and 12.5 mg/day in patients with a serum creatinine level of greater than 2-3 and 4-6 mg/dL, respectively, in order to maintain a plasma level equivalent to that in subjects with normal renal function receiving 50 mg/day alacepril. For patients on chronic hemodialysis, 12.5 mg alacepril is the appropriate dose.
authors: Department of Nephrology, Kumamoto University Graduate School of Medical Science, Japan. nono@kumamoto-u.ac.jp
authors: Hiroshi
authors: H
authors: Nonoguchi
authors: Shigeru
authors: S
authors: Kiyama
authors: Kenichiro
authors: K
authors: Kitamura
authors: Masahiro
authors: M
authors: Naruse
authors: Masao
authors: M
authors: Tomita
authors: Noboru
authors: N
authors: Tazoe
authors: Munemasa
authors: M
authors: Tajiri
authors: Yushi
authors: Y
authors: Nakayama
authors: Yukimasa
authors: Y
authors: Kohda
authors: Takeaki
authors: T
authors: Inoue
authors: Kimio
authors: K
authors: Tomita
mesh_terms: D000375:Aging / Q000502:physiology; D000465:Algorithms; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage* / Q000097:blood* / Q000627:therapeutic use; D001835:Body Weight / Q000502:physiology; D002216:Captopril / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use; D003401:Creatine / Q000097:blood; D003404:Creatinine / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000209:etiology; D007676:Kidney Failure, Chronic / Q000150:complications / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D002216:Captopril; D003404:Creatinine; D003401:Creatine; C046835:alacepril