Population Pharmacokinetics of Procainamide from Routine Clinical Data

Authors: Grasela TH, Sheiner LB
Publication: Clin Pharmacokinet
Keywords: analysis, arrhythmia, biological, cardiology, cardiovascular agents, congestive, drug therapy, female, heart, heart failure, humans, kinetics, male, metabolism, middle-aged, models, P.H.S., pharmacokinetics, plasma, population, procainamide, research support, therapeutic use, U.S. Government
Division: Clinical Pharmacology and Pharmacometrics (CPP)

Abstract

Routine clinical pharmacokinetic data collected from patients receiving procainamide were analysed to estimate population pharmacokinetic parameters. 116 plasma concentration determinations for procainamide and 14 timed urine collections for the drug and its major metabolite N-acetylprocainamide (NAPA) were obtained from 39 patients, mostly males. The data were analysed using NONMEM, a computer program designed for population pharmacokinetic analysis that allows pooling of data from many individuals. Estimates of the influence of weight, height, renal function, and the presence of congestive heart failure (CHF) on the renal clearance (CLR), acetylation clearance (CLA), miscellaneous metabolic clearance (CLO), and volume of distribution (Vd) of procainamide were obtained.

The mean (SE) CLR, CLA, CLO and Vd for procainamide in a 70kg patient with normal renal function were estimated to be 14.4 (2.3) L/h, 10.1 (1.7) L/h, 1.2 (1.3) L/h, and 136.0 (20.0) L, respectively. These pharmacokinetic parameters vary linearly with bodyweight; height adds no information if weight is known. The presence of CHF has no significant effect on either CLO or Vd, but reduces CLA and CLR by 11% (p < 0.01). Even after adjustments for CHF, renal function and weight, the total clearance and Vd of procainamide vary unpredictably among individuals, with a coefficient of variation between 30 and 40%, and < 50%, respectively.

By Thaddeus H. Grasela, & Lewis B. Sheiner