TABLE 1

Residual activities of estradiol 3-O-glucuronide formation in human liver microsomes and recombinant UGT1A1 in the presence of 15 compounds that are substrates of UGTs, the kinetic parameters of the 15 compounds in human liver microsomes, and the main isoforms involved in the glucuronidation

Residual activities of estradiol 3-O-glucuronide formation in human liver microsomes and recombinant UGT1A1 were determined in the presence of 15 kinds of compounds (100 μM). Control activities for estradiol 3-O-glucuronide formations in HLMs and by recombinant UGT1A1 are described in Fig. 1 legend. The data are the means ± S.D. of three independent determinations.


Compound

Residual Activity

Km

Vmax

Vmax/Km

Isoform

HLMs
UGT1A1




% μM nmol/min/mg μl/min/mg
Group A
    Acetaminophen 92 ± 4 94 ± 4 4100a 1.5a 0.4 1A6a
    Furosemide 82 ± 6 76 ± 5 950b 0.1b 0.1b 1A9, 2B7c
    Ibuprofen 79 ± 2 78 ± 4 188d 0.7d 3.5d 2B7e
    Imipramine 92 ± 2 88 ± 4 1000b 0.4b 0.4b 1A4c
    Ketoprofen 86 ± 4 80 ± 8 1600b 0.4b 0.2b 1A9, 2B7c
    Mycophenolic acid 84 ± 2 82 ± 3 180f 5.2f 28.7f 1A9, 2B7f
    Serotonin 90 ± 6 96 ± 5 8800g 43.4g 4.9 1A6g
    Valproic acid 95 ± 3 96 ± 2 4475b 0.9b 0.2b 1A6, 1A9, 2B7h
Group B
    Ethynylestradiol 24 ± 7 20 ± 3 205b 0.1b 0.7b 1A1c
    Propofol 23 ± 9 18 ± 9 235i 3.8i 16 1A9c
    Tranilast 27 ± 7 17 ± 8 52j 0.01j 0.2 1A1j
Group C
    4-Methylumbelliferone 52 ± 7* 64 ± 1 143k 72.1k 504 1A6k
    1-Naphthol 56 ± 7* 84 ± 2 42i 17.5i 417 1A6l
    2-Naphthol 57 ± 7* 76 ± 2 12m 31.2m 2600m 1A6n
    4-Nitrophenol
79 ± 6*
97 ± 2
308k
69.2k
225
1A6k
  • * P < 0.05, compared with that by recombinant UGT1A1.

  • a Fisher et al. (2000).

  • b Soars et al. (2001).

  • c McGinnity et al. (2004).

  • d Kuehl et al. (2005).

  • e Iyer et al. (2003).

  • f Picard et al. (2005).

  • g Krishnaswamy et al. (2003).

  • h Ethell et al. (2003).

  • i Soars et al. (2003).

  • j Katoh et al. (2007).

  • k Hanioka et al. (2001a).

  • l Uchaipichat et al. (2004).

  • m The parameters were determined in the present study.

  • n de Wildt et al. (1999).