Table 1

Effects of quinidine on the 4′- and 10-hydroxylation of warfarin in incubations with human liver microsomes or hepatocytes

Incubation System1-b CYP3A4 Activity10-Hydroxylation1-a 4′-Hydroxylation1-a
nmol/min/mg1-c pmol/min/mg % Control pmol/min/mg % Control
HLM160 (M)0.51.06700.5100
HLM162 (M)2.37.25200.9270
HLM163 (M)0.93.05000.5240
HLM166 (F)2.43.08700.4420
HLM167 (F)3.216.24402.2220
HLM mixture1.86.45000.9350
HLcell-1 (F)225210
HLcell-2 (F)470250
HLcell-3 (M)240270
  • 1-a  For incubations with human liver microsomes, warfarin (racemic) in methanol and quinidine in water were added to a final concentration of 100 μM. For incubations with human hepatocytes, warfarin (racemic) in dimethyl sulfoxide and quinidine in water were added to a final concentration of 50 μM. Controls contained no quinidine but the same amount of methanol or dimethyl sulfoxide. Incubations were performed in duplicates. % Control was based on the formation of 4′- and 10-hydroxywarfarin in test incubations relative to the values in control experiments that lacked quinidine.

  • 1-b  HLM160 to 167 represent liver microsomal preparations from three male (M) and two female (F) donors; HLM mixture represents pooled liver microsomes; HLcell represents hepatocytes from male (M) or female (F) donors.

  • 1-c  The activity of CYP3A4 in human liver microsomes was evaluated based on the 6β-hydroxylation of testosterone.