Clinical pharmacokinetics of procainamide infusions in relation to acetylator phenotype

The pharmacokinetics of procainamide was determined in 21 lidocaine-resistant patients who received the drug according to a pharmacokinetically designed double-infusion technique. Thirteen patients were phenotyped as slow acetylators, seven as fast, and one as intermediate. The total body clearances (ClT) of PA in slow and fast acetylators were 22.6 and 34.8 liters/hr, respectively. The fraction of PA cleared by the formation of NAPA in the corresponding acetylator group was 0.2 and 0.4. Renal impairment affected the pharmacokinetics of PA more profoundly as the ClTs of PA in patients with and without renal impairment were 17.9 and 31.2 liters/hr, respectively. None of the calculated volumes of distribution was affected by acetylator phenotype or renal impairment. These data identify the contribution of at least two of the major factors accounting for variability in PA disposition in patients undergoing therapy.

[1]  L. Nelson,et al.  Kinetics of procainamide and N-acetylprocainamide in renal failure. , 1977, Kidney international.

[2]  A. Atkinson,et al.  Antiarrhythmic potency of N‐acetylprocainamide , 1975, Clinical pharmacology and therapeutics.

[3]  B. Johansson,et al.  Effects of long-term treatment with procaine amide. A prospective study with special regard to ANF and SLE in fast and slow acetylators. , 2009, Acta medica Scandinavica.

[4]  H. Pieniaszek,et al.  Salivary excretion and pharmacokinetics of sulfapyridine after sulfasalazine , 1977, Clinical pharmacology and therapeutics.

[5]  J. Swarbrick.  Drugs and the pharmaceutical sciences , 1975 .

[6]  T. Gibson,et al.  Acetylation of procainamide in man and its relationship to isonicotinic acid hydrazide acetylation phenotype , 1975, Clinical pharmacology and therapeutics.

[7]  W. Jusko,et al.  Determination of procainamide acetylator status , 1978, Clinical pharmacology and therapeutics.

[8]  J. Koch-weser,et al.  Procainamide dosage schedules, plasma concentrations, and clinical effects. , 1971, JAMA.

[9]  E. Genton,et al.  Pharmacokinetics of procainamide. , 1972, Archives of internal medicine.

[10]  D. Drayer,et al.  Polymorphic acetylation of procainamide in man , 1975, Clinical pharmacology and therapeutics.

[11]  Carl V. Manion,et al.  Absorption kinetics of procainamide in humans. , 1977, Journal of pharmaceutical sciences.

[12]  L B Sheiner,et al.  Relationship between the pharmacokinetics and pharmacodynamics of procainamide , 1976, Clinical pharmacology and therapeutics.

[13]  P. Souich,et al.  Patterns of acetylation of procainamide and procainamide-derived p-aminobenzoic acid in man , 1976, European Journal of Clinical Pharmacology.

[14]  J. Oates,et al.  Effect of acetylator phenotype on the rate at which procainamide induces antinuclear antibodies and the lupus syndrome. , 1978, The New England journal of medicine.

[15]  W. Jusko,et al.  Pharmacokinetic approach to intravenous procainamide therapy , 1978, European Journal of Clinical Pharmacology.

[16]  V. Hansteen,et al.  Comparison of the acetylation of procainamide and sulfadimidine in man , 1976, European Journal of Clinical Pharmacology.

[17]  R. Kehoe,et al.  Antiarrhythmic efficacy of N‐acetylprocainamide in patients with premature ventricular contractions , 1976, Clinical pharmacology and therapeutics.

[18]  L. Benet,et al.  The renal elimination of procainamide , 1976, Clinical pharmacology and therapeutics.

[19]  J. Bigger,et al.  Metabolism of procainamide in normal and cardiac subjects , 1976, Clinical pharmacology and therapeutics.

[20]  Milo Gibaldi,et al.  Drugs and the pharmaceutical sciences , 1975 .

[21]  C. Graffner.  Elimination rate ofN-acetylprocainamide after a single intravenous dose of procainamide hydrochloride in man , 1975, Journal of Pharmacokinetics and Biopharmaceutics.

[22]  A. Atkinson,et al.  Dose‐ranging trial of N‐acetylprocainamide in patients with premature ventricular contractions , 1977, Clinical pharmacology and therapeutics.

[23]  J. Strong,et al.  Pharmacokinetics in man of the N-acetylated metabolite of procainamide. , 1975, Journal of pharmacokinetics and biopharmaceutics.

[24]  G. W. Snedecor.  Statistical Methods , 1964 .

[25]  A. Atkinson,et al.  Pharmacokinetics in man of theN-acetylated metabolite of proeainamide , 1975, Journal of Pharmacokinetics and Biopharmaceutics.

[26]  A. Atkinson,et al.  Procainamide and N‐acetylprocainamide kinetics investigated simultaneously with stable isotope methodology , 1977, Clinical pharmacology and therapeutics.

[27]  W. Weber,et al.  Dose‐dependent changes in sulfamethazine kinetics in rapid and slow isoniazid acetylators , 1978, Clinical pharmacology and therapeutics.