The effects of encainide versus diltiazem on the oxidative metabolic pathways of antipyrine.
The effects of diltiazem and encainide on the pharmacokinetics and metabolism of antipyrine were compared in nine healthy male volunteers. Diltiazem 90 mg every 8 hours for 5 days decreased the oral clearance of antipyrine from 2.34 to 1.86 L/hour (p less than 0.05) and increased half-life from 12.7 to 15.9 hours (p less than 0.05). Diltiazem reduced the formation rate constants for 3-hydroxymethylantipyrine by 27% (p less than 0.05) and 4-hydroxyantipyrine by 37% (p less than 0.05). There was also a 21% reduction in the formation rate constant for norantipyrine (0.05 less than p less than 0.10). Encainide 25 mg every 8 hours for 5 days had no apparent effect on the oral clearance or half-life of antipyrine, or on the formation rate constants for metabolites of antipyrine. In contrast to a previously published report in rats, encainide, unlike diltiazem, does not inhibit the oxidative metabolism of antipyrine in humans.
Bottorff
M B
MB
Division of Clinical and Hospital Pharmacy, University of Cincinnati, Ohio 45267.
Lalonde
R L
RL
Kazierad
D J
DJ
Hoon
T J
TJ
Tsiu
S J
SJ
Mirvis
D M
DM
D000328:Adult; D000813:Anilides / Q000494:pharmacology*; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D000983:Antipyrine / Q000378:metabolism* / Q000493:pharmacokinetics; D004110:Diltiazem / Q000494:pharmacology*; D004347:Drug Interactions; D016700:Encainide; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D010084:Oxidation-Reduction / Q000187:drug effects; D011897:Random Allocation
D000813:Anilides; D000889:Anti-Arrhythmia Agents; D004110:Diltiazem; D016700:Encainide; D000983:Antipyrine