Flecainide distribution in human tissues.

Abstract

The distribution of antiarrhythmic drugs in human tissues may yield a better understanding of their therapeutic action and side effects. We report tissue distribution of flecainide in a patient who died suddenly while being treated chronically with the drug. Lungs showed the highest concentration of flecainide (143 micrograms g‐1 wet tissue); liver, kidney and heart, in decreasing order, have good affinity for the drug. Flecainide was present also in the central nervous system in lower concentrations. The lowest concentration was found in the adipose tissue.

Effects of CYP2D6 genotypes on age‐related change of flecainide metabolism: involvement of CYP1A2‐mediated metabolism

“…Chemical inhibition of MODF formation was examined by incubation of flecainide (50 µM) and pooled microsomes in the presence of CYP‐selective inhibitors: furafylline (25 µM) for CYP1A2, sulfaphenazole (25 µM) for CYP2C9, omeprazole (10 µM) for CYP2C19, paroxetine (10 µM) for CYP2D6, and ketoconazole (5 µM) for CYP3A4. The 50 µM flecainide corresponded to the concentration in the liver under repeated administration of flecainide in clinical practice [17]. Mechanism‐based inhibitors (furafylline and paroxetine) were preincubated with microsomes and the NADPH‐regeneration system at 37 °C for 15 min.…”

Drug-induced acute pneumonitis following initiation of flecainide therapy after pulmonary vein isolation ablation in a patient with mitral stenosis and previous chronic amiodarone use

“…This mechanism involves phagocytosis of antigen by an antigen-presenting cell macrophage, monocyte, or dendritic cell and presenting it to T cells 4 . Flecainide in particular has high affinity for concentrating in lung tissue 5 . It is interesting to speculate whether chronic accumulation of amiodarone (well known to cause different types of pulmonary toxicity) could have influenced the severity of or accelerated this immune process after flecainide exposure in our patient.…”

Involvement of Renal Efflux Transporter MATE1 in Renal Excretion of Flecainide

“…Unbound C max / IC 50 , which was 0.07 based on unbound fraction of 0.42, 4) was over 0.02 as the cutoff value for further in vivo evaluation. 10) Moreover the reported renal tissue concentration of flecainide is considerably higher (50 µM) than the serum concentration. 11) Therefore, the in vivo drug-drug interaction study of flecainide with substrates of hMATE1 may be needed.…”