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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

In vitro drug interaction between diflunisal and indomethacin via glucuronidation in humans.

It was reported that the plasma concentration of indomethacin was increased with concomitant oral dosages of diflunisal in humans. Both indomethacin and diflunisal are glucuronidated in humans. The effects of diflunisal on the indomethacin glucuronidation were thus investigated in vitro using human liver microsomes (HLM) and human intestine microsomes (HIM) in order to assess the drug-drug interaction. The glucuronidation of indomethacin in HLM showed atypical kinetics with K(m) and K(si) values of 210 and 89.5 microM, respectively, while HIM exhibited Michaelis-Menten kinetics with a K(m) value of 17.4 microM. Diflunisal inhibited the indomethacin glucuronidation in HLM with IC(50) values ranging from 100 to 231 microM. In HIM, inhibition of the indomethacin glucuronidation by diflunisal was more potent with IC(50) values of 15.2-48.7 microM. When the clinical dose of diflunisal (250 mg b.i.d.) is taken into consideration, it is expected that the diflunisal concentration in the intestine would be higher than the IC(50) values for indomethacin glucuronidation in the intestine. These findings suggest that the clinical drug-drug interaction between diflunisal and indomethacin may be at least partly attributable to the inhibition of indomethacin glucuronidation by diflunisal in the intestine. Copyright (c) 2006 John Wiley & Sons, Ltd.[1]


  1. In vitro drug interaction between diflunisal and indomethacin via glucuronidation in humans. Mano, Y., Usui, T., Kamimura, H. Biopharmaceutics & drug disposition. (2006) [Pubmed]
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