Publications

The kinetic behavior of N-acetylprocainamide (NAPA) was studied after single and repeated oral doses in six healthy subjects and five patients with cardiomyopathy. Renal clearance (CLR) of NAPA was lower in patients than in normal subjects after an initial 1-gm dose (1.3 +/- 0.4 [x +1- SD] and 2.7 +/- 0.4 ml . min-1 . kg-1, P less than or equal to 0.001) and a final 2 gm dose (1.6 +/- 0.4 and 2.6 +/- 0.5 ml . min-1 . kg-1, P less than or equal to 0.01) even though there was no difference between measured creatinine clearance (ClCR) 80.8 +/- 23.6 and 93.2 +/- 19.3 ml . min-1 [1.73 M2]-1). The decrease in the ratio of NAPA ClR to ClCR (R) could not be accounted for by age alone. A published regression formula overestimated the R ratio for patients (1.65 +/- 0.09 and 1.25 +/- 0.17, P less then 0.025), but accurately predicted the R ratio for healthy subjects (2.10 +/- 0.04 and 1.99 +/- 0.54). Mean steady-state concentration (normalized for daily dose per unit of body mass) after 2 gm every 8 hr for at least 3 days was higher for patients (P less than or equal to 0.05). Comparing the parameters for all subjects after the initial 1-gm dose to those after the last 2-gm dose with paired data, oral clearance was somewhat lower after the last dose (3.7 +/- 1.0 and 3.1 +/- 1.0 ml . min-1 . kg-1, P less than or equal to 0.01). In spite of this, before and 2 hr after dose steady-state NAPA serum concentration were generally proportional to dose over the concentration range studied. Net deacetylation of NAPA to procainamide in both groups was minimal.