Flecainide pharmacokinetics in healthy volunteers: the influence of urinary pH

The pharmacokinetics of a single 300 mg oral dose of flecainide were studied in eight healthy volunteers on four separate occasions under different conditions of urinary pH. The urinary pH of the volunteers was manipulated chemically to produce four distinct groups spanning the range of urinary pH (pH 5-8). Neither the rate nor extent of flecainide absorption was significantly affected by changes in urinary pH. However the plasma elimination of flecainide was found to be inversely proportional to urinary pH and the volunteers' mean elimination half-life ranged between 10.7 +/- 3.2 h (s.d.) at the extreme acid pH and 17.6 +/- 6.3 h at the extreme alkali pH. The urinary elimination and renal clearance of flecainide decreased with increasing urinary pH. The influence of changes in urinary pH on the pharmacokinetics of flecainide will contribute to the normal variability in flecainide serum concentrations seen in patients and should be considered in patients who have adverse reactions to the drug at low dosage or who fail to respond at high doses.