Summary
A pharmacokinetic approach was employed to design a dosing regimen for the i. v. use of procainamide (PA) which consisted of a loading infusion given over one hour followed by a maintenance infusion. Therapeutic serum concentrations of PA were achieved in less than 15 min, and toxic serum concentrations were avoided in 12 patients. A mean maximum serum concentration of PA of 5.78 mg/l was obtained with a loading infusion of 16.6 mg/min PA HCl. An average steady-state serum concentration of PA of 5.05 mg/l was obtained with a mean maintenance infusion of 222 mg/hour PA HCl. The total body clearance of PA in slow and fast acetylators averaged 31 and 43 l/h respectively. Use of PA in cardiac patients by i. v. infusion can be safe and effective therapy.
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References
Koch-Weser, J., Klein, S.W., Foo-Canto, L.L.: Anti-arrhythmic prophylaxis with procainamide in acute myocardial infarction. New Engl. J. Med.218, 1253–1260 (1969)
Koch-Weser, J.: Correlation of serum concentrations and pharmacological effects of anti-arrhythmic drugs. Proc. 5th Congress Pharmacol., San Francisco, Vol.3, 69–85 (1972)
Stearns N.S., Callahan E.J., Eillis L.B.: Value and hazards of intravenous procainamide therapy. J. Amer. med. Ass.148, 360–364 (1952)
Berry K., Garrett E.L., Bellet S.: The use of Pronestyl in treatment of ectopic rhythms: 98 episodes in 78 patients. Amer. J. Med.11, 431–441 (1951)
Epstein M.A.: Ventricular standstill during intravenous procainamide treatment of ventricular tachycardia. Amer. Heart J.45, 898–907 (1953)
Giardina E.G., Heissenbuttel, R.H., Bigger, J.T.: Intermittent intravenous procainamide to treat ventricular arrhythmias. Ann. Int. Med.78, 183–193 (1973)
Koch-Weser, J.: The pharmacokinetics of anti-arrhythmic drugs. In: Innovations in the Diagnosis and Management of Acute Myocardial Infarction. (ed. A.N. Brest, L. Wiener, E.K. Chung, H. Kasparian) Philadelphia: F. A. Davis. Cardiovasc. Clin.7, 191–202 (1975)
Wagner, J.G.: A safe method for rapidly achieving plasma concentration plateaus. Clin. Pharmacol. Ther.16, 691–700 (1974)
Gibaldi, M., Perrier, D.: Pharmacokinetics. New York: Marcel Dekker, Inc., 1975
Metzler, C.M.: NONLIN: A computer program for parameter estimation in nonlinear situations. Technical Report # 7292/69/7292/005. Kalamazoo, Michigan: The Upjohn Company, Nov. 25, 1969
Galeazzi, R.L., Benet, L.Z., Sheiner, L.B.: Relationship between the pharmacokinetics and pharmacodynamics of procainamide. Clin. Pharmacol. Ther.20, 278–289 (1976)
Reidenberg, M.M., Drayer, D.E., Levy, M., Warner, H.: Polymorphic acetylation of procainamide in Man. Clin. Pharmacol. Ther.17, 722–730 (1975)
Strong, J.M., Dutcher, J.S., Lee, W., Atkinson, A.J.: Pharmacokinetics in man of the N-acetylated metabolite of procainamide. J. Pharmacokin. Biopharm.3, 223–234 (1975)
Lima, J., Jusko, W.J.: Micromethod for procainamide and its acetylated metabolite by high performance liquid chromatography, in Liquid Chromatography Symposium I: Biological/Biomedical Applications of Liquid Chromatography. New York: Marcel Dekker, Inc, (in press)
Lima, J., Jusko, W.J.: Determination of procainamide acetylator status. Clin. Pharmacol. Ther.23, 25–29 (1978)
Koch-Weser, J.: Clinical application of the pharmacokinetics of procainamide. Cardiovasc. Clin.6, 63–75 (1974)
Koch-Weser, J., Klein, S.W.: Procainamide dosage schedules, plasma concentrations, and clinical effects. J. Amer. Med. Ass.215, 1454–1460 (1971)
Karlsson, E., Kinman, A., Sonnhag, C.: Comparative evaluation of phenytoin, procainamide and practolol in the acute treatment of ventricular arrhythmias. Europ. J. clin. Pharmacol.11, 1–6 (1977)
Schwartz, M.L., Covina, B.G.: The anti-arrhythmic activity of intravenous procainamide, pp. 67–83. Princeton, New Jersey: Excerpta Medica, 1976
Gibson, T.P., Matusik, J., Matusik, E., Nelson, H.A., Wilkinson, J., Briggs, A.: Acetylation of procainamide in man and its relationship to isonicotinic acid hydrazine acetylation phenotype. Clin. Pharmacol. Ther.17, 395–399 (1975)
Simions, K.J., Levy, R.H., Cutler, R.E., Graham, T., Linder, C., Linder, A.: The pharmacokinetics of procainamide in normal subjects using a specific gas chromatographic assay. Res. Comm. Chem. Path. Pharmacol.11, 173 (1975)
Lee, W.K., Strong, J.M., Kehoe, R.F., Dutcher, J.S., Atkinson, A.J.: Anti-arrhythmic efficacy of N-acetyl procainamide in patients with premature ventricular contractions. Clin. Pharmacol. Ther.19, 508–514 (1977)
Atkinson, A.J., Lee, W.K., Quinn, M.L., Kuschner, W., Nevin, M.J., Strong, J.M.: Dose-ranging trial of N-acetyl procainamide in patients with premature ventricular contractions. Clin. Pharmacol. Ther.21, 575–587 (1977)
Reidenberg, M.M., Martin, J.H.: The acetylator phenotype of patients with systemic lupus erythematosus. Drug Disposition2, 71–73 (1974)
Gibson, T.P., Matusik, E.J., Briggs, W.A.: N-acetyl procainamide levels in patients with end-stage renal failure. Clin. Pharmacol. Ther.19, 206–212 (1976)
Campbell, W., Tilstone, W.J., Lawson, D.H., Hutton, I., Lawrie, T.D.V.: Acetylator phenotype and the clinical pharmacology of slow release procainamide. Brit. J. Clin. Pharmacol.3, 1023–1026 (1976)
du Souich, P., Frill, S.; Patterns of acetylation of procainamide and procainamide-derived p-aminobenzoic acid in man. Europ. J. Clin. Pharmacol.9, 433–438 (1976)
Freeman, R., Harbison, R., Woosley, R., Oates, J.: A proposed reactive metabolite of procainamide in procainamide-induced systemic lupus erythematosus. Fed. Proc.36, 97 (1977)
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Lima, J.J., Conti, D.R., Goldfarb, A.L. et al. Pharmacokinetic approach to intravenous procainamide therapy. Eur J Clin Pharmacol 13, 303–308 (1978). https://doi.org/10.1007/BF00716367
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DOI: https://doi.org/10.1007/BF00716367