Pharmacokinetics of flecainide in patients with cirrhosis of the liver

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Abstract
The pharmacokinetics of flecainide were studied in six patients with cirrhosis of the liver and in six healthy subjects after a single 2 mg/kg intravenous dose. Hepatic biotransformation capability before flecainide dosing was assessed by antipyrine challenge. The mean plasma antipyrine t1/2 for patients (42.2 hours) was longer (p < 0.01) than that for subjects (11.7 hours). For control subjects, the plasma t1/2 of flecainide (9.5 hours) was shorter (p < 0.01), plasma clearance (9.1 ml/min/kg) was faster (p < 0.01), and volume of distribution (7.5 L/kg) was smaller (p < 0.05) compared with corresponding values in patients. Renal clearance did not differ (p > 0.05) between the two groups. The mean ratio of renal clearance to plasma clearance for subjects (0.4) was smaller (p < 0.05) than that for patients. The slower rate of flecainide elimination from plasma in patients is likely due to reduced hepatic biotransformation. In patients with cirrhosis, plasma levels of flecainide may accumulate to unacceptably high levels with usual doasage regimens.