Altered pharmacokinetics of oral flecainide by cimetidine

A potential kinetic interaction between cimetidine and flecainide has been studied in eight healthy males receiving flecainide (200 mg) orally on three occasions: before any treatment and on day 2 and day 7 of 8 days' cimetidine maintenance treatment at 1 g daily. Six days pretreatment with cimetidine induced the following changes in flecainide kinetic parameters: average tmax was prolonged from 1.8 h to 3.6 h and total AUC increased significantly from 4779 to 6131 ng ml-1 h. Plasma elimination half-life and renal clearance were not significantly altered. The fraction of flecainide dose excreted unchanged in urine rose significantly from 31 to 38%. The observed interaction can be explained by an increase in bioavailability or, more probably, by a decrease in biotransformation of flecainide in the presence of cimetidine.