Fenamates and the potent inhibition of human liver phenol sulphotransferase

1. The inhibition of the human liver phenol sulphotransferase (HL-PST) and catechol sulphotransferase (HL-CST) by five fenamates has been studied and the activities of HL-PST and I-IL-CST were measured with 4-nitrophenol and dopamine as substrates, respectively. 2. The IC50 for inhibition of HL-PST were 0.02 mu M (mefenamic acid); 0.12 mu M (tolfenamic acid); 0.28 mu M (niflumic acid); 0.87 mu M (meclofenamic acid) and 1.50 mu M (mefenamic acid). 3. HL-CST was less susceptible than HL-PST to the inhibition by fenamates a nd the IC50 for HL-CST were 36 mu M (tolfenamic acid); 70 mu M (flufenamic acid); 76 mu M (mefenamic acid); 180 mu M (niflumic acid) and 185 mu M (mec lofenamic acid). 4. The ratios of the IC50 for HL-CST:HL-PST were drug-dependent and ranged from 47 (flufenamic acid) to 3800 (mefenamic acid). Mefenamic acid is a rel atively potent and selective inhibitor of HL-PST. 5. The IC50 for HL-PST obtained with mefenamic acid was three orders of mag nitude lower than the peak plasma concentration of this drug after an oral dose of 0.5 g. Accordingly, mefenamic acid should impair sulphation in vivo .