Pharmacokinetics of Procainamide and N-acetylprocainamide during Continuous Renal Replacement Therapy

dc.contributor.authorMohamed, Ahmed N.
dc.contributor.authorAbdelhady, Ahmed M.
dc.contributor.authorSpencer, Dustin
dc.contributor.authorSowinski, Kevin M.
dc.contributor.authorTisdale, James E.
dc.contributor.authorOverholser, Brian R.
dc.contributor.departmentMedicine, School of Medicine
dc.date.accessioned2025-05-12T13:27:29Z
dc.date.available2025-05-12T13:27:29Z
dc.date.issued2013
dc.description.abstractProcainamide 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.
dc.eprint.versionAuthor's manuscript
dc.identifier.citationMohamed AN, Abdelhady AM, Spencer D, Sowinski KM, Tisdale JE, Overholser BR. 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;61(6):1046-1048. doi:10.1053/j.ajkd.2013.02.358
dc.identifier.urihttps://hdl.handle.net/1805/47969
dc.language.isoen_US
dc.publisherElsevier
dc.relation.isversionof10.1053/j.ajkd.2013.02.358
dc.relation.journalAmerican Journal of Kidney Diseases
dc.rightsPublisher Policy
dc.sourcePMC
dc.subjectAcecainide
dc.subjectChronic renal insufficiency
dc.subjectVentricular tachycardia
dc.subjectProcainamide
dc.titlePharmacokinetics of Procainamide and N-acetylprocainamide during Continuous Renal Replacement Therapy
dc.typeArticle
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