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Moricizine Concentration to Guide Arrhythmia Treatment: With Attention to Elderly Patients
Author(s) -
Giardina ElsaGrace V.,
Wechsler Mindy E.,
Dolgopiatova Maria,
Sciacca Robert
Publication year - 1994
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/j.1552-4604.1994.tb02032.x
Subject(s) - medicine
To test the relationship between plasma moricizine concentration and the electrocardiogram (ECG) and arrhythmia suppression, 17 symptomatic cardiac patients with 30 or more ventricular premature complexes per hour were studied. Seven patients were mature adults, less than 60 years of age; and ten were elderly adults, more than 60 years of age. During steady‐state moricizine therapy, patients had plasma moricizine concentration determined over a dosing interval, and had standard 12‐lead ECG and a 24‐hour ambulatory ECG recorded. The mean moricizine dose was 215 ± 29 mg every 8 hours; mean maximal moricizine concentration was 1.4 ± 0.84 μg/ml; and mean t 1/2β was 1.5 ± 0.7 hours. Baseline age‐related differences were found, including prolonged electrocardiographic intervals (PR and QRS) (P < .05 ), increased ventricular arrhythmias (P < .05 ), and reduction in creatinine clearance (P < .05 ) in the elderly. Compared with pretreatment values, PR (P < .05 ) and QRS (P < .05 ) prolongation was observed, and was more marked in elderly patients. Over a dosing interval, there were dynamic changes on the ECG that paralleled plasma moricizine concentration; that is, peak and nadir intact moricizine concentration occurred simultaneously with ECG changes: QRS and JTc prolonged (P < .05 ), and PR prolongation approached significance (P = 0.09 ). Suppression of ventricular premature complexes of 80% or more occurred in 15 patients, and ventricular tachycardia was abolished in 10 of 12 patients. Probit analysis revealed that the therapeutic antiarrhythmic concentration ranged from 0.20 to 3.6 μg/ml. After treatment, there was no difference for area under the plasma concentration curve, half life of elimination, or volume of distribution in: (1) mature adults younger than 60 years versus elderly adults 60 years of age or older, nor (2) patients with ejection fraction of 35% or lower versus those with ejection fraction higher than 35%. Intact plasma moricizine concentration accounts for dynamic electrocardiographic and antiarrhythmic effects after use of the drug. Cautious administration of moricizine in older patients is warranted in view of age‐related baseline differences in cardiac conduction, as well as more marked effects on PR and QRS duration; and potential toxicity secondary to diminished drug clearance .