J. Koch-weser
Jul 1, 1971
Citations
4
Influential Citations
124
Citations
Quality indicators
Journal
Annals of the New York Academy of Sciences
Abstract
Procainamide has been widely used in the past two decades as an effective drug for the prevention or treatment of active cardiac arrhythmias. Despite this common clinical use, little attention has been given to its pharmacokinetics in man. Clinical experience has shown that dosages required to achieve satisfactory results and tolerated without toxic manifestations vary considerably among patients. Until recently, concentrations of procainamide in blood or plasma had rarely been determined during its clinical use and had not been correlated with its therapeutic and toxic effects.'-3 It is becoming increasingly clear that the therapeutic effectiveness and toxic effects of many drugs are much better correlated with their blood concentration than with their dosage. Activity of most drugs depends on their concentration at the site of action, and this concentration will generally show a fairly constant relationship to the concentration of the drug in body water. On the other hand, the relationship between the dosage administered and the concentration of most drugs in body water is highly variable. It is influenced by the completeness of absorption, by the characteristics of distribution, and by the rates of metabolism and excretion. All of these are subject to much individual and temporal variation. In extensive clinical studies we found plasma concentrations of procainamide to correlate satisfactorily with the therapeutic and toxic effects of the drug in These data are summarized in FIGURE 1. Plasma concentrations between 4 and 8 mg/l constitute the usually effective therapeutic range. In occasional patients, higher concentrations yield a better therapeutic effect, but toxic effects may appear at levels above 8 mg/l. At concentrations exceeding 16 mg/l, manifestations of toxicity in the electrical and mechanical performance of the heart and hemodynamic disturbances are the rule. The good correlation between plasma concentrations and clinical effects of procainamide lent added interest to its pharmacokinetics. Better understanding of the variables that alter the relationship between dosage and plasma concentrations promised to be clinically valuable. We have measured procainamide concentrations in plasma and urine and performed kinetic studies in 186 patients and seven volunteers. Procainamide concentrations were determined in parallel by previously described spectrophotometric and spectrophotofluorometric method^.^'^ Both methods are specific, highly reproducible, and sensitive to 0.05 mg/l, and were always in excellent agreement. They are technically simple and inexpensive. It should be emphasized that all concentrations are given as procainamide base and that plasma concentrations of procainamide are higher than blood concentrations (procainamide concentration plasma/erythrocytes = 1.58).