In order to evaluate the concentration-response relationship for either antiarrhythmic or electrocardiographic (ECG) effects, 13 patients with stable and frequent (>100/hour) premature ventricular contractions (PVCs) were selected and flecainide (FLE) was administered as acute oral dose (200 mg) and as chronic treatment (150 mg b.i.d, for 21 days), followed by wash out. In each phase Holter monitoring, serial ECG tracings and serum samples for FLE concentrations were performed. The relationships between FLE concentrations and either ECG effects or antiarrhythmic efficacy, analysed by calculation of the minimal effective concentration (efficacy = reduction > 90% of PVCs), were assessed. Results: QRS and PR intervals lengthened significantly either after acute oral administration or after chronic treatment by 21-36% (mean values) and QRS interval changes were significantly related to serum FLE concentrations (r = 0.68, p < 0.001 in acute and r = 0.79, p < 0.001 in chronic administration). However, the relationship between FLE concentrations and QRS intervals percentual lengthening showed a reduction in the slope of the regression lines in chronic vs. acute treatment (average of the individual values = 7.7 ± 4.0% ml.μg in acute versus 3.8 ± 1.1% ml.μg in chronic, p < 0.001), thus indicating a relative reduction during chronic treatment of the drug effects on ECG intervals. Antiarrhythmic efficacy was reached in 8/13 patients in acute and in 11/13 patients in chronic without significant differences in FLE minimal effective concentrations (acute = 262 ± 119 ng/ml, chronic = 319 ± 276 ng/ml, n.s.). In conclusion during chronic treatment with FLE a dissociation between ECG and antiarrhythmic effects occurs, with a relative reduction in the extent of QRS lengthening at a given FLE concentration but without changes in the relationship between FLE concentrations and antiarrhythmic effects. This finding limits the clinical usefulness of QRS intervals changes monitoring during treatment with FLE.
|Data di pubblicazione:||1993|
|Titolo:||Flecainide: Evidence of different concentration-response relationships for antiarrhythmic and electrocardiographic effects|
|Autore/i:||Boriani, G.; Capucci, A.; Strocchi, E.; Santarelli, A.; Spedicato, L.; Biffi, M.; Magnani, B.|
|Citazione:||Flecainide: Evidence of different concentration-response relationships for antiarrhythmic and electrocardiographic effects / Boriani, G.; Capucci, A.; Strocchi, E.; Santarelli, A.; Spedicato, L.; Biffi, M.; Magnani, B.. - In: NEW TRENDS IN ARRHYTHMIAS. - ISSN 0393-5302. - 9:4(1993), pp. 999-1003.|
|Tipologia||Relazione in Atti di Convegno|
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