PMID- 2511912
OWN - NLM
STAT- MEDLINE
DCOM- 19900116
LR  - 20190510
IS  - 0306-5251 (Print)
IS  - 1365-2125 (Electronic)
IS  - 0306-5251 (Linking)
VI  - 28
IP  - 5
DP  - 1989 Nov
TI  - Stereoselective disposition of flecainide in relation to the 
      sparteine/debrisoquine metaboliser phenotype.
PG  - 555-66
AB  - 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-dealkylated flecainide (MODF) and the meta-O-dealkylated lactam of 
      flecainide (MODLF) were lower (P less than 0.05) in PMs, 12.0% +/- 3.1% and 8.2% 
      +/- 3.2% of the dose administered, respectively, than in EMs of 17.7% +/- 3.3% 
      and 16.5% +/- 3.3%, respectively. 5. One PM subject had a greatly diminished 
      flecainide metabolic capacity and a rare genotype, as assigned by Xbal RFLP 
      analysis.
FAU - Gross, A S
AU  - Gross AS
AD  - Dr Margarete Fischer-Bosch-Institut fur Klinische Pharmakologie, Stuttgart, FRG.
FAU - Mikus, G
AU  - Mikus G
FAU - Fischer, C
AU  - Fischer C
FAU - Hertrampf, R
AU  - Hertrampf R
FAU - Gundert-Remy, U
AU  - Gundert-Remy U
FAU - Eichelbaum, M
AU  - Eichelbaum M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Br J Clin Pharmacol
JT  - British journal of clinical pharmacology
JID - 7503323
RN  - 0 (Isoquinolines)
RN  - 298897D62S (Sparteine)
RN  - K94FTS1806 (Flecainide)
RN  - X31CDK040E (Debrisoquin)
SB  - IM
MH  - Debrisoquin/*metabolism
MH  - Female
MH  - Flecainide/metabolism/*pharmacokinetics
MH  - Genotype
MH  - Humans
MH  - Isoquinolines/*metabolism
MH  - Male
MH  - Phenotype
MH  - Sparteine/*metabolism
MH  - Stereoisomerism
PMC - PMC1380016
EDAT- 1989/11/01 00:00
MHDA- 1989/11/01 00:01
PMCR- 1990/05/01
CRDT- 1989/11/01 00:00
PHST- 1989/11/01 00:00 [pubmed]
PHST- 1989/11/01 00:01 [medline]
PHST- 1989/11/01 00:00 [entrez]
PHST- 1990/05/01 00:00 [pmc-release]
AID - 10.1111/j.1365-2125.1989.tb03542.x [doi]
PST - ppublish
SO  - Br J Clin Pharmacol. 1989 Nov;28(5):555-66. doi: 
      10.1111/j.1365-2125.1989.tb03542.x.