Pharmacokinetic modeling and simulation of procainamide and N-acetylprocainamide in a patient receiving continuous renal replacement therapy: a novel approach to guide renal dose adjustments

Am J Kidney Dis. 2013 Jun;61(6):1046-8. doi: 10.1053/j.ajkd.2013.02.358. Epub 2013 Apr 4.

Abstract

Procainamide and its major metabolite, N-acetyl procainamide (NAPA), prolong the QTc interval and can promote potentially fatal ventricular arrhythmias. Excretion of procainamide and NAPA is reduced in patients with chronic kidney disease (CKD) resulting in drug accumulation and toxicity. The elimination of procainamide or NAPA in patients undergoing continuous renal replacement therapy (CRRT) has not been evaluated increasing the risk for subtherapeutic or toxic dosing regimens. This case report describes a patient undergoing CRRT who was administered procainamide for recurring ventricular tachycardia (VT) over approximately a 36 hour period. The patient required increased vasopressor therapy and developed QTc prolongation during procainamide administration. The VT resided following pacemaker adjustments, procainamide administration, and multiple direct current cardioversion attempts. Procainamide and NAPA concentrations were determined over a 120 hour period as part of routine clinical care and a pharmacokinetic (PK) model was developed using NONMEM. The developed PK model was used to simulate several procainamide dosing regimens to optimize therapy during CRRT. Based on the model-based simulations, a 50% reduction in the procainamide maintenance dose (2 mg/min) in CKD patients on CRRT can achieve therapeutic plasma procainamide and combined procainamide/NAPA concentrations.

Publication types

  • Case Reports
  • Letter
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acecainide / pharmacokinetics*
  • Adult
  • Anti-Arrhythmia Agents / pharmacokinetics*
  • Humans
  • Male
  • Models, Biological
  • Procainamide / pharmacokinetics*
  • Renal Insufficiency, Chronic / complications
  • Renal Insufficiency, Chronic / metabolism
  • Renal Insufficiency, Chronic / therapy*
  • Renal Replacement Therapy / methods*
  • Tachycardia, Ventricular / complications
  • Tachycardia, Ventricular / drug therapy*

Substances

  • Anti-Arrhythmia Agents
  • Acecainide
  • Procainamide