PMID- 1906003
OWN - NLM
STAT- MEDLINE
DCOM- 19910814
LR  - 20190813
IS  - 0031-6970 (Print)
IS  - 0031-6970 (Linking)
VI  - 40
IP  - 2
DP  - 1991
TI  - Polymorphic flecainide disposition under conditions of uncontrolled urine flow 
      and pH.
PG  - 155-62
AB  - The pharmacokinetics of R- and S-flecainide have been determined in five poor 
      (PM) and five extensive (EM) metabolisers of sparteine/debrisoquine under 
      conditions of uncontrolled urine flow and pH. The half-lives of R- and 
      S-flecainide in PMs (R 19.3 h; S 16.1 h) were approximately twice those observed 
      in EMs (R 8.8 h; S 9.1 h). The apparent oral clearances of R- and S-flecainide 
      were lower in PMs (R 313 ml.min-1; S 379 ml.min-1) than in EMs (R 783 ml.min-1; S 
      828 ml.min-1). The renal clearance, however, was comparable for both enantiomers 
      in both EMs and PMs, and therefore the phenotypic differences in flecainide 
      disposition observed must be due to differences in metabolic clearance. The 
      nonrenal clearance of both enantiomers was significantly lower in poor (R 123 
      ml.min-1; S 201 ml.min-1) relative to extensive metabolisers (R 533 ml.min-1; S 
      586 ml.min-1). The partial clearance to the two major metabolites 
      meta-O-dealkylated flecainide (MODF) and the meta-O-dealkylated lactam of 
      flecainide (MODLF) was significantly lower in poor (62 ml.min-1) than extensive 
      (267 ml.min-1) metabolisers. The impairment in flecainide metabolism in poor 
      metabolisers of sparteine/debrisoquine has therefore been confirmed. Under 
      conditions reflecting the clinical situation the difference in disposition 
      between EMs and PMs would be considerable. However, it may be predicted that at 
      standard doses concentrations greater than 1000 ng.ml-1 would not be attained in 
      the PMs studied.(ABSTRACT TRUNCATED AT 250 WORDS)
FAU - Gross, A S
AU  - Gross AS
AD  - Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, FRG.
FAU - Mikus, G
AU  - Mikus G
FAU - Fischer, C
AU  - Fischer C
FAU - Eichelbaum, M
AU  - Eichelbaum M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Germany
TA  - Eur J Clin Pharmacol
JT  - European journal of clinical pharmacology
JID - 1256165
RN  - 298897D62S (Sparteine)
RN  - K94FTS1806 (Flecainide)
RN  - X31CDK040E (Debrisoquin)
SB  - IM
MH  - Adult
MH  - Analysis of Variance
MH  - Dealkylation
MH  - Debrisoquin/metabolism
MH  - Female
MH  - Flecainide/*pharmacokinetics
MH  - Half-Life
MH  - Humans
MH  - Hydrogen-Ion Concentration
MH  - Male
MH  - Polymorphism, Genetic
MH  - Protein Binding
MH  - Sparteine/metabolism
MH  - Stereoisomerism
MH  - Urination
EDAT- 1991/01/01 00:00
MHDA- 1991/01/01 00:01
CRDT- 1991/01/01 00:00
PHST- 1991/01/01 00:00 [pubmed]
PHST- 1991/01/01 00:01 [medline]
PHST- 1991/01/01 00:00 [entrez]
AID - 10.1007/BF00280070 [doi]
PST - ppublish
SO  - Eur J Clin Pharmacol. 1991;40(2):155-62. doi: 10.1007/BF00280070.