Pharmacokinetic and Pharmacodynamic Studies of Procainamide / Pa / and N-Acetylprocainamide / Napa /

Wierzchowiecki, M; Michałowska, D; Łowicki, Zdzisław; Ochotny, Romuald; Grześkowiak, A

doi:10.1016/b978-0-08-023768-8.52514-7

Cited by 1 publication

(1 citation statement)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…the rate of production) and its clearance. Early in the course of therapy, concentrations will be low, but because the half-life of N-acetylprocainamide is longer than that of procainamide, there will be further accumulation (Dutcher et aI., 1977;Wierzchowiecki et al, 1980). There are large interindividual variations in the concentrations of Nacetylprocainamide, but it clearly accumulates during renal failure (Drayer et aI., 1977), as normally 85 % is eliminated by renal excretion.…”

Section: Plasma Levels Qf Metabolitesmentioning

confidence: 96%

Therapeutic Drug Monitoring of Antiarrhythmic Agents

Brown

Shand

1982

Clinical Pharmacokinetics

View full text Add to dashboard Cite

Therapeutic drug monitoring has come of age in clinical medicine and, in particular, its use with antiarrhythmic agents has flourished. The classic indications for the use of therapeutic drug monitoring are commonly encountered with antiarrhythmic drug use. Most of the currently available allliarrhythmics have a narrow therapeutic index, necessitating car~ful dose titration. The ~rfectiveness of these agents in clinical use isfrequent(v d([ficultlo determine as a result of marked variability in arrhythmia frequency or i l1 frequelll events. Thus, therapeutic drug monitoring seems appropriate for adjusting therapy in arrhythmia prophylaxis or in the prevention (if sudden death. Most antiarrhythmic agents appear to have generally accepted therapeutic ranges, a prerequisite for therapeutic drug monitoring. The historical determina' tion of the therapeutic range for each of the allliarrhythmics will be discussed in addition 10 the numerous factors affecting the d~finition (if this range for any drug, including type (if arrhythmia, aetiology of underlying cardiac disease, the concept (if true individual dose ranging, adequate control periods, the definition of true drug efficacy and the quantitation (if arrhythmia frequency (including 24-hour ECG recording with computer-assisted analysis and the invasive technology (if programmable velllricular stimulation), and the roles of protein binding, drug interactions and active metabolites.In addition to these considerations, therapeutic drug monitoring is particularly us~ful in this drug class because of marked illlerindividual variability in pharmacokinetic parameters including absorption, clearance and volume of distribution, resulting in variable dose-concelli ration relationships. This information can be useful in distinguishing between true therapeutic failures and inadequate plasma concelllrations.The therapeutic concentration range of quinidine appears to be 1 to 5pg/mlutilising newer, more specific assay techniques, but the accepted range is very dependent on the type of assay. There is wide interindividual variability in the optimal drug concentration with toxicity occurringfrom Jpg/ml. The ~[feclive concentration range for procainamide is 4 to 10pg/ml, with early toxicity commencing at 8 to IOllg/ml and progressively increasing with further increments in plasma concentration. However, some patients may respond to higher concelllrations without experienCing toxicity. The therapeutic concentration range for N-acetylprocainamide is not clearly defined, but appears to be greater than IOpg/ ml with toxicity occurring over a wide range (if concelllrations (10 to 40pg/ ml). As yet, there is no sati~factory method to deal with combined procainamide and N-acetylprocainamide concentrations.

show abstract

Section: Plasma Levels Qf Metabolitesmentioning

confidence: 96%