Serum disopyramide concentrations and suppression of ventricular premature contractions

Serum disopyramide determinations and 24‐hour Holter monitoring were performed in 20 cardiac subjects with ventricular premature contractions (VPCs) after the first, seventeenth, and thirty‐seventh doses of disopyramide, 100 mg (10 subjects; low‐dose group) or 200 mg (10 subjects; high‐dose group) every 6 hr for 10 days to assess the ability of single‐ or first‐dose data to predict serum disopyramide concentrations at steady state and the relationship between steady‐state serum disopyramide concentrations and VPC suppression. Control Holter recordings were made for 48 hr in each subject. There were strong correlations in both groups between data for the AUC over 0 to 6 hr for the first dose (AUC 6 0 ) and average (C̄ ss ) and trough (C min ) steady‐rate serum disopyramide concentrations after the seventeenth and thirty‐seventh doses and the two combined. C̄ ss and C min were related to AUC 6 0 by the following expressions for both dosage groups: C̄ ss = 0.22 AUC 6 0 + 0.90 and Ĉ min = 0.20 AUC 6 0 + 0.70. There were good correlations between 6‐hr serum disopyramide concentration after the first dose and C̄ ss and C min . There was strong correlation between overall average steady‐state serum disopyramide concentration and suppression of VPC frequency. The relationship between VPC suppression and overall average trough serum disopyramide concentration at steady state, on the other hand, was weak. Clinical Pharmacology and Therapeutics (1984) 36, 326–336; doi: 10.1038/clpt.1984.183