[Concentrations of amiodarone and flecainide in plasma and saliva--indications for the active transport of flecainide].

in Zeitschrift fur Kardiologie (1988), 77(2), 99-102

Only the free protein-unbound drug concentration in plasma is pharmacologically active. The concentration of some drugs in saliva is equal to the free drug level. We compared concentrations (in plasma ... [more ▼]

Only the free protein-unbound drug concentration in plasma is pharmacologically active. The concentration of some drugs in saliva is equal to the free drug level. We compared concentrations (in plasma before, 30 and 60 min after the morning dose, in saliva before, 30, 60, 90 and 120 min after the morning dose) of amiodarone (n = 8, 2 x 200 mg orally per day) and flecainide (n = 16, 2 x 100 mg) administered as chronic antiarrhythmic treatment. Drug levels were measured by "high performance liquid chromatography". Results: Just prior to the first morning dose, amiodarone concentrations in plasma were 1.0-2.9 (2.0 +/- 0.6) micrograms/ml, in saliva 0.02-0.25 micrograms/ml; flecainide in plasma 80-560 (316 +/- 163) ng/ml, in saliva 630-3700 (1749 +/- 963) ng/ml. After the morning dose we found maximal flecainide plasma levels of 462 +/- 203 and saliva levels of 3218 +/- 2857 ng/ml. The highest flecainide concentrations in the saliva (13,400 and 11,300 ng/ml) were found in two patients 30 and 60 min after the morning dose. Flecainide, but not amiodarone, is excreted actively in the saliva, probably indicating an enteroenteric circulation. This should be considered to reduce life-threatening flecainide intoxications by gastric and intestinal lavage and suction. The concentration of flecainide in the saliva does not represent the non-protein-bound free drug level in the plasma. [less ▲]

[Elevated plasma flecainide concentrations in heart failure].

in Deutsche medizinische Wochenschrift (1946) (1987), 112(44), 1698-700

In 42 patients with heart failure who were on long-term treatment with flecainide (2 X 100 mg daily by mouth) plasma concentration of flecainide was measured before the morning dose and compared with the ... [more ▼]

In 42 patients with heart failure who were on long-term treatment with flecainide (2 X 100 mg daily by mouth) plasma concentration of flecainide was measured before the morning dose and compared with the clinical grade of heart failure or left ventricular ejection fraction (in the levo-angiogram). Mean plasma flecainide concentration was 415 +/- 244 ng/ml (110-1035 ng/ml), mean ejection fraction 55 +/- 17.7% (24-84%) (r = -0.60). In seven patients with plasma concentrations over 700 ng/ml (870 +/- 150 ng/ml) in clinical grade III or IV, ejection fractions were 24, 25, 25, 30, 33, 37 and 44%, respectively. In two patients (ejection fraction of 24 and 25%, respectively) the morning plasma concentration was around 1000 ng/ml. The results point to possible high plasma flecainide concentrations--at times in the toxic range--in patients who are in heart failure. In patients with marked reduction in left ventricular pumping function who are on long-term flecainide treatment, a reduction in dosage or monitoring of plasma flecainide concentration is indicated. [less ▲]