Clinical Pharmacokinetics of Intravenous Flecainide in Critically Ill Patients

Abstract

Plasma flecainide (FLC) levels versus time were measured in a group of 10 acute myocardial infarction (AMI) patients at our Intensive Care Unit. These patients were treated with single doses of 150 mg FLC as a 30-min intravenous infusion. Mean FLC plasma concentration values at 0, 1, 2, 4, and 8 h following administration were 562 +/- 271, 342 +/- 129, 270 +/- 90m, 240 +/- 80 and 210 +/- 60 ng/ml, respectively. Flecainide pharmacokinetics fitted an open two-compartment model, with a rapid distribution phase and a slow elimination phase. Mean values for the terminal plasma half-life (t1/2 beta) was 22.0 +/- 9.7 h and the volume of distribution (V beta) was 7.99 +/- 3.02 1/kg. FLC is different to other i.v. antiarrhythmics in having a prolonged plasma half-life which is a decided advantage. In contrast to lidocaine, FLC has a pharmacokinetic profile that enables it to be used for treating ventricular arrhythmia without constant-rate i.v. infusion and without the need for complicated loading dosages in order to avoid a 'pharmacokinetic dip' over the first hour of treatment.

Paranoid Psychosis and Myoclonus: Flecainide Toxicity in Renal Failure

“…When available, the plasma flecainide levels in these patients were 1,730, 2,500 and 4,000 µg/l, compared with a lower level of 1,270 µg/l in our patient. It has been noted that plasma levels of above 700–1,000 µg/l are associated with increased likelihood of adverse events [9,10,11]. …”

“…Haemodialysis removes only about 1% of an oral dose as unchanged flecainide [9] as it has a large volume of distribution due to extensive tissue binding [10, 11]. Up to 50% of flecainide is bound to the α 1 -glycoprotein.…”