Stereoselective disposition of flecainide in relation to the sparteine/debrisoquine metaboliser phenotype

British Journal of Clinical Pharmacology
A S GrossM Eichelbaum

Abstract

1. The disposition of the enantiomers of the antiarrhythmic drug flecainide has been studied in five extensive (EM) and five poor (PM) metabolisers of sparteine/debrisoquine after administration of 50 mg of racemic flecainide acetate under conditions of high urinary flow rate and acidic urinary pH. 2. In the EM subjects there were no significant differences in the oral clearance, half-life or urinary excretion of (+)-S- and (-)-R-flecainide. 3. In the PM subjects differences in the pharmacokinetics of S- and R-flecainide were observed. The oral clearance of R-flecainide (467 +/- 109 ml min-1) was less (P less than 0.03) than that of the S-enantiomer (620 +/- 172 ml min-1). The half-life of R-flecainide (12.9 h) was longer (P less than 0.03) than that of S-flecainide (9.8 h). The renal clearance of the two enantiomers was, however, comparable and similar to that observed in the EM subjects. The urinary recovery of R-flecainide (15.6 +/- 3.7 mg) was greater (P less than 0.03) than that of the S-enantiomer (12.0 +/- 3.7 mg). The enantioselective disposition observed in PMs is therefore due to greater impairment in the metabolism of R- than S-flecainide. 4. The urinary recoveries of two major metabolites of flecainide, meta-O-dealk...Continue Reading

References

Oct 1, 1979·Journal of Pharmacokinetics and Biopharmaceutics·C C Peck, B B Barrett
Jan 1, 1990·Pharmacology & Therapeutics·M Eichelbaum, A S Gross
May 1, 1989·Clinical Pharmacology and Therapeutics·G MikusM Eichelbaum
Jul 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·R C SkodaU A Meyer
Oct 30, 1987·Deutsche medizinische Wochenschrift·J NitschB Lüderitz
Mar 1, 1988·Journal of Clinical Pharmacology·S C ForlandG J Conard
Nov 1, 1988·Clinical Pharmacology and Therapeutics·R L McQuinnG J Conard
Nov 19, 1988·BMJ : British Medical Journal·J BeckmannM Eichelbaum
Apr 1, 1988·British Journal of Clinical Pharmacology·M EichelbaumC O Meese
Jul 3, 1986·The New England Journal of Medicine·D M Roden, R L Woosley
Jul 1, 1986·Clinical Pharmacology and Therapeutics·D M SalernoM Hodges
Nov 15, 1985·Klinische Wochenschrift·C ZekornM Eichelbaum
Apr 1, 1984·British Journal of Clinical Pharmacology·K A MuhiddinP Turner
Feb 27, 1984·The American Journal of Cardiology·G J Conard, R E Ober
Dec 1, 1983·Clinical Pharmacology and Therapeutics·M S LennardH F Woods

❮ Previous
Next ❯

Citations

Feb 1, 1992·Journal of Clinical Pharmacology·R J Guttendorf, P J Wedlund
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
Oct 15, 1990·Clinica Chimica Acta; International Journal of Clinical Chemistry·J P FrecheG Siest
Jan 1, 1990·Pharmacology & Therapeutics·M Eichelbaum, A S Gross
Dec 1, 1992·Trends in Pharmacological Sciences·S CholertonJ R Idle
Dec 1, 1993·Journal of the American College of Cardiology·C LibersaM Lhermitte
Mar 1, 1992·British Journal of Clinical Pharmacology·U M BirgersdotterD M Roden
Oct 1, 1990·Pharmacology & Toxicology·M S Lennard
Jan 28, 2004·Annual Review of Pharmacology and Toxicology·Susan M Abdel-Rahman, Ralph E Kauffman
Jul 10, 2002·Clinical Pharmacokinetics·Reza MehvarMajid Vakily
Oct 13, 2009·Clinical Pharmacokinetics·Shu-Feng Zhou
Nov 6, 1998·British Journal of Clinical Pharmacology·T J Campbell, K M Williams
Sep 1, 1994·Journal of Clinical Pharmacology·D G May
Jun 1, 1993·Cardiovascular Drugs and Therapy·L Arcavi, N L Benowitz
Jun 12, 2009·Drug Metabolism Reviews·Shu-Feng ZhouBalram Chowbay
Aug 1, 1997·Drug Metabolism Reviews·S Garattini
Jan 1, 1990·Journal of Toxicology. Clinical Toxicology·C KöppelG Heinemeyer
Jan 11, 2005·The Journal of Pharmacy and Pharmacology·Masato HommaYukinao Kohda
Aug 8, 2009·British Journal of Clinical Pharmacology·Kosuke DokiYukinao Kohda
Jul 22, 2015·Drug Metabolism and Pharmacokinetics·Kosuke DokiMasato Homma
Jun 1, 1990·Cardiovascular Drugs and Therapy·R L Woosley
Jan 8, 2003·Biopharmaceutics & Drug Disposition·Peter H Hinderling
Sep 1, 2006·Biopharmaceutics & Drug Disposition·Dion R Brocks
Aug 30, 2008·British Journal of Clinical Pharmacology·Kyoung Soo LimKyung-Sang Yu
Nov 29, 2017·European Journal of Clinical Pharmacology·Sijie LuA S Gross
May 12, 2020·Environmental Science & Technology·Jonas MechelkeJuliane Hollender

❮ Previous
Next ❯

Related Concepts

Related Feeds

Arrhythmia

Arrhythmias are abnormalities in heart rhythms, which can be either too fast or too slow. They can result from abnormalities of the initiation of an impulse or impulse conduction or a combination of both. Here is the latest research on arrhythmias.

Anti-Arrhythmic Drug Therapies

Anti-arrhythmic drugs are used to prevent abnormal heart rhythms. These medications are used in conditions including, ventricular tachycardia, ventricular fibrillation and atrial fibrillation. Discover the latest research on anti-arrhythmic drug therapies here.

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.