GLUCURONIDATION OF 7-HYDROXY-4-METHYLCOUMARIN BY HUMAN LIVER-MICROSOMES - INHIBITION BY CERTAIN DRUGS

Glucuronidation of 7-hydroxy-4-methylcoumarin (7-OH-4-MC) was comparable in three of the four human liver samples studied. In liver sample IV the glucuronidation rate of 7-OH-4-MC was almost 40% of that in the other samples. That might be due to interindividual variation in the capacity to glucuronidate. Glucuronidation rates were not reduced in the one human liver sample which displayed mild centrilobular cholestasis on histopathology. Furosemide (FR), salicylic acid (SA), lorazepam (Z) and menthol (MT) inhibited the glucuronidation of 7-OH-4-MC to varying degrees (30-90%). Paracetamol (PA) and 5-hydroxytryptamine (HT) were not inhibitors of the glucuronidation of 7-OH-4-MC. These findings suggest the presence of other UDP-glucuronosyltransferase (UDPGT) isozymes in the human liver microsomes which are responsible for the glucuronidation of PA and HT than those which glucuronidate 7-OH-4-MC.