[Concentrations of amiodarone and flecainide in plasma and saliva--indications for the active transport of flecainide].
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.
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000638:Amiodarone / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001145:Arrhythmias, Cardiac / Q000097:blood*; D001693:Biological Transport, Active; D005260:Female; D005424:Flecainide / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006352:Heart Ventricles / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D011485:Protein Binding; D012463:Saliva / Q000378:metabolism*
D005424:Flecainide; D000638:Amiodarone
Konzentrationen von Amiodaron und Flecainid im Plasma und im Speichel--Hinweise für einen aktiven Transport von Flecainid.