Oral Flecainide Pharmacokinetics in Patients with Impaired Renal Function

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Abstract
The pharmacokinetics of flecainide acetate were studied in 20 patients with varying degrees of renal impairment following a single oral dose. The patients were divided into two groups, on the basis of renal creatinine clearance (CLCR), for statistical and kinetic analysis. Patients with a CLCR between 4 and 41 mL/min/m2 were designated group 1 and those below 4 mL/min/m2 or unmeasurable because of lack of urine output were designated group 2. In both groups peak plasma flecainide concentrations, time to peak concentrations, and apparent volume of distribution (Vd) were similar to those reported in healthy subjects with normal renal function. The mean flecainide plasma elimination half‐lives from both groups 1 and 2 were longer than those previously reported by several investigators in normal subjects. Nine patients in group 1 and seven patients in group 2 had half‐lives within the range reported in healthy subjects. Therefore, CLCR alone is not a good predictor of plasma elimination half‐life following a single oral dose of flecainide. Although renal clearance of flecainide is significantly reduced in end‐stage renal disease (ESRD), total plasma clearance of flecainide (CLflec) was not reduced to the same degree, although there was a significant, modest correlation with CLCR. Less than 1% of the administered oral dose of flecainide was removed during hemodialysis. The relationship between dosage and plasma elimination half‐life in patients with ESRD needs further study to evaluate possible dose‐dependent kinetics.