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Pharmacokinetics of flecainide in patients with cirrhosis of the liver
Author(s) -
McQuinn R L,
Pentikäinen P J,
Chang S F,
Conard G J
Publication year - 1988
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1988.195
Subject(s) - flecainide , pharmacokinetics , volume of distribution , cirrhosis , plasma clearance , medicine , dosing , plasma levels , plasma concentration , pharmacology , distribution (mathematics) , metabolic clearance rate , gastroenterology , endocrinology , atrial fibrillation , mathematical analysis , mathematics
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 t ½ for patients (42.2 hours) was longer ( p < 0.01) than that for subjects (11.7 hours). For control subjects, the plasma t ½ 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 dosage regimens. Clinical Pharmacology and Therapeutics (1988) 44, 566–572; doi: 10.1038/clpt.1988.195