TABLE 4

Inhibition of NSAID glucuronidation in pooled HLMs by UGT-selective probes

Rates were determined at NSAID concentrations from 10 to 500 μM under the following conditions: 1 mg/ml protein, 50 μg of alamethicin/mg HLM protein, 1 mM PMSF, 8.5 mM saccharolactone, 2 mM UDP-glucuronic acid, and 10 mM MgCl2 in 50 mM potassium phosphate, pH 7, with and without 5 μM bilirubin or 50 μM estradiol, imipramine, propofol, HDCA, or morphine. Values are reported as percentage of inhibition.


[NSAID]

Bilirubin (1A1)

Estradiol (1A1/2B7)

Imipramine (1A3)

Propofol (1A9)

HDCA (2B4/2B7)

Morphine (2B7)
Sulindac
    10 μM 20 55 NI 22 73 66
    500 μM NI 34 NI 51 76 70
Sulindac sulfone
    10 μM 29 51 NI NI 53 16
    500 μM 13 27 NI NI 51 NI
Indomethacin
    10 μM NI 54 NI 25 42 NI
    500 μM NI 31 NI 18 48 NI
Ibuprofen
    10 μM 15 42 37 26 59 21
    500 μM 28 67 16 35 50 13
Flurbiprofen
    10 μM 25 61 18 15 55 17
    500 μM NI 60 21 26 35 NI
Ketoprofen
    10 μM 23 54 25 40 44 NI
    500 μM 15 42 NI NI 29 NI
Diclofenac
    10 μM NI 21 NI NI 21 NI
    500 μM NI 13 15 14 NI NI
Naproxen
    10 μM 18 63 NI 32 62 29
    500 μM
26
41
NI
27
36
20
  • NI, no inhibition (inhibition less than 10%).