Disposition of procainamide in patients with chronic congestive heart failure receiving medical therapy.
Dosage reduction of procainamide has been recommended in patients with congestive heart failure (CHF). However, these recommendations are based primarily on studies with unmatched control groups, suboptimal blood sampling, and in patients not receiving angiotensin-converting enzyme (ACE) inhibitors. These agents increase renal blood flow, which theoretically may offset alterations in drug disposition in patients with CHF. The pharmacokinetics of procainamide in patients with chronic CHF and in matched controls were compared. A single intravenous dose of 750 mg of procainamide was administered to 9 patients with chronic New York Heart Association (NYHA) class II or III CHF (mean +/- SD left ventricular ejection fraction 22 +/- 9%) receiving medical therapy and 7 control subjects matched for age and gender. Blood and urine samples were collected at intervals over a period of 48 and 72 hours, respectively. Patients with CHF and control subjects were demographically similar, with the exception of concomitant medications, including ACE inhibitors (8/9 versus 1/7, respectively). There were no significant differences between patients with CHF and control subjects in mean +/- SD peak serum concentrations (Cmax), area under the serum concentration-time curve (AUC0-infinity), total clearance, renal clearance, half-life (t1/2), or volume of distribution (Vd) of procainamide. Similarly, there were no significant differences between patients with CHF and control subjects in the mean +/- SD Cmax, AUC0-infinity, renal clearance, or t1/2 of N-acetylprocainamide (NAPA). Procainamide dosage reduction may not be necessary in patients with chronic stable CHF who are receiving medical therapy.
Tisdale
J E
JE
College of Pharmacy and Allied Health, Wayne State University, Detroit, MI 48202, USA.
Rudis
M I
MI
Padhi
I D
ID
Borzak
S
S
Svensson
C K
CK
Webb
C R
CR
Acciaioli
J
J
Ware
J A
JA
Krepostman
A
A
Zarowitz
B J
BJ
D000328:Adult; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004077:Digoxin / Q000627:therapeutic use; D004232:Diuretics / Q000627:therapeutic use; D005260:Female; D006333:Heart Failure / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011342:Procainamide / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use
D000806:Angiotensin-Converting Enzyme Inhibitors; D000889:Anti-Arrhythmia Agents; D004232:Diuretics; D004077:Digoxin; D011342:Procainamide