The influence of the sparteine/debrisoquin phenotype on the disposition of flecainide

Clinical Pharmacology and Therapeutics
G MikusM Eichelbaum

Abstract

The pharmacokinetics and urinary excretion of flecainide (50 mg administered orally) were investigated in five extensive metabolizers (EMs) and five poor metabolizers (PMs) of the sparteine/debrisoquin type of polymorphism under conditions of controlled urinary pH. Flecainide disposition was altered in the PMs. The AUC was higher (1462 +/- 407 versus 860 +/- 256 hr ng/ml), the elimination half-life prolonged (11.8 versus 6.8 hours), and the amount excreted in the urine was higher (26.7 +/- 7.2 versus 15.4 +/- 1.3 mg) in PMs compared with EMs (p less than 0.05). Oral clearance of flecainide was reduced (p less than 0.019) in PMs (600 +/- 139 versus 1041 +/- 307 ml/min in EMs). The renal clearance was similar (p greater than 0.05) in PMs (308 +/- 70 ml/min) and EMs (315 +/- 69 ml/min) and, consequently, PMs had a lower (p less than 0.008) metabolic clearance of flecainide (292 +/- 136 versus 726 +/- 240 ml/min in EMs). Under conditions of uncontrolled urinary flow and pH, renal excretion of flecainide will be reduced and the difference in disposition will be greater. In PMs with renal impairment, accumulation of flecainide to very high serum concentrations may be anticipated, and this may result in proarrhythmic effects.

Citations

Nov 6, 1998·British Journal of Clinical Pharmacology·T J Campbell, K M Williams
Feb 21, 2002·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Zeruesenay DestaD A Flockhart
Nov 11, 2003·Clinical Pharmacokinetics·Susan E TettAndrew J McLachlan
Jul 20, 2007·Arteriosclerosis, Thrombosis, and Vascular Biology·Donna K Arnett, UNKNOWN American Heart Association Writing Group
Nov 8, 2007·The Annals of Pharmacotherapy·Milo Gibaldi
Jan 1, 1992·The Annals of Pharmacotherapy·M Gibaldi
Nov 1, 1994·Journal of Cardiovascular Electrophysiology·R H Falk, R I Fogel
Jun 1, 1993·Cardiovascular Drugs and Therapy·L Arcavi, N L Benowitz
Sep 1, 1994·Journal of Clinical Pharmacology·D G May
Dec 4, 2003·European Journal of Clinical Investigation·I Cascorbi
Apr 15, 2015·European Journal of Clinical Pharmacology·Juan TamargoPhillipe Mabo
Nov 1, 1989·British Journal of Clinical Pharmacology·A S GrossM Eichelbaum
Mar 1, 1992·British Journal of Clinical Pharmacology·U M BirgersdotterD M Roden
Jan 8, 2003·Biopharmaceutics & Drug Disposition·Peter H Hinderling
Aug 8, 2009·British Journal of Clinical Pharmacology·Kosuke DokiYukinao Kohda
Jan 11, 2005·The Journal of Pharmacy and Pharmacology·Masato HommaYukinao Kohda
Feb 24, 2001·Therapeutic Drug Monitoring·K MamiyaN Tashiro
Jun 12, 2009·Drug Metabolism Reviews·Shu-Feng ZhouBalram Chowbay
Oct 13, 2009·Clinical Pharmacokinetics·Shu-Feng Zhou
Oct 1, 1990·Pharmacology & Toxicology·M S Lennard
Sep 14, 2006·Pharmacological Reviews·Sharon J Gardiner, Evan J Begg
Jan 1, 1991·European Journal of Clinical Pharmacology·G BorianiB Magnani
Jan 1, 1992·European Journal of Clinical Pharmacology·A MunafoJ Biollaz
Sep 1, 2006·European Journal of Clinical Pharmacology·Kosuke DokiYukinao Kohda
Mar 1, 1991·Biochemical Pharmacology·G MikusM Eichelbaum

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antiarrhythmic Agents: Mechanisms of Action

Understanding the mechanism of action of antiarrhythmic agents is essential in developing new medications as treatment of cardiac arrhythmias is currently limited by the reduced availability of safe and effective drugs. Discover the latest research on Antiarrhythmic Agents: Mechanism of Action here.