Table 1

Kinetic parameters for the glucuronidation of 16 compounds in human and dog liver microsomes

CompoundHLMDLM
VmaxKmCLintVmaxKmCLint
nmol/min/mg μM μl/min/mg nmol/min/mg μM μl/min/mg
Androstanediol2.3, 2.3160, 19014, 1211, 14410, 46027, 30
Bilirubin1-a 0.48, 0.527, 1169, 470.07, 0.0427, 102.6, 4.0
Codeine1-b 0.24, 0.25580, 5200.41, 0.481.6, 1.8350, 3704.7, 4.8
Ethynylestradiol1-a 0.13, 0.13240, 1700.54, 0.760.81, 0.72130, 796.5, 9.1
Furosemide0.12, 0.12890, 10100.13, 0.121.1, 0.71490, 11000.74, 0.64
Gemfibrozil1-b 0.58 ± 0.06240 ± 152.4 ± 0.35.3, 6.0200, 19027, 31
Hydromorphone1-b 1.1, 1.3890, 11201.2, 1.216, 21570, 61028, 35
Hyodeoxycholic acid5.0, 4.9360, 38014, 131.3, 1.1150, 1208.5, 9.2
Imipramine0.39, 0.411000, 10000.39, 0.41<0.01N.D.N.D.
Ketoprofen1-b 0.34, 0.361460, 17400.23, 0.213.2, 2.61210, 9002.7, 2.9
Morphine (3 gluc)1-b 0.76, 0.67440, 4701.7, 1.432, 401530, 13021, 32
Morphine (6 gluc)1-b 0.12, 0.14400, 3000.30, 0.47N.D.N.D.N.D.
Naloxone1-b 0.48 ± 0.08870 ± 1100.55 ± 0.19.3, 8.71260, 12907.4, 6.8
1-Naphthol7.3, 7.6460, 44016, 1769, 61200, 160350, 390
Naproxen1-b 0.21 ± 0.03560 ± 900.38 ± 0.04 2.1 ± 0.45760 ± 2302.8 ± 0.9
Propofol0.09, 0.2164, 641.4, 3.3N.D.N.D.N.D.
Valproic acid1-b 0.86, 0.894190, 47600.21, 0.19 2.5 ± 0.541420 ± 5601.9 ± 0.9

Data are from individual expts. (each expt. was a kinetic curve produced using six substrate concentrations in duplicate) or mean ± S.D. (three individual expts.). HLM were produced by pooling microsomes prepared from six human livers, each one characterized as shown in Fig.1. DLM were prepared from the liver of a single beagle dog.

  • N.D., below the level of detection (8 pmol/min/mg).

  • ↵1-a  Compounds shown to be metabolized by human UGT1A1 (Ebner et al., 1993).

  • ↵1-b  Compounds shown to be metabolized selectively by Human UGT2B7 (Coffman et al., 1997;Terrier et al., 1999).