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The influence of the sparteine/debrisoquin phenotype on the disposition of flecainide
Author(s) -
Mikus Gerd,
Gross Annette S,
Beckmann Jürgen,
Hertrampf Rita,
GundertRemy Ursula,
Eichelbaum Michel
Publication year - 1989
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.1989.73
Subject(s) - flecainide , pharmacokinetics , urine , disposition , pharmacology , sparteine , urinary system , chemistry , medicine , psychology , social psychology , organic chemistry , atrial fibrillation
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 < 0.05). Oral clearance of flecainide was reduced (p < 0.019) in PMs (600 ± 139 versus 1041 ± 307 ml/min in EMs). The renal clearance was similar (p > 0.05) in PMs (308 ± 70 ml/min) and EMs (315 ± 69 ml/min) and, consequently, PMs had a lower (p < 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. Clinical Pharmacology and Therapeutics (1989) 45, 562–567; doi: 10.1038/clpt.1989.73