TABLE 2

Effect of organic solvents on the kinetics of CYP2C8-mediated paclitaxel hydroxylation in the presence of HLM

Kinetic parameters are expressed as % Control (mean ± S.D.)



Solvent (%, v/v)

Methanol
Ethanol
Acetonitrile
DMSO
K m
0 (Control) 100.0 ± 1.4 100.0 ± 3.2 100.0 ± 2.2 100.0 ± 4.0
0.2 67.8 ± 1.7a 165.3 ± 12.1b 101.9 ± 0.5 123.7 ± 2.4b
0.5 65.1 ± 2.4a 303.4 ± 14.5a 101.5 ± 0.1 128.8 ± 8.0b
1 N.E. N.E. 92.9 ± 16.5 N.E.
2 132.0 ± 7.6b 507.4 ± 26.5a 132.3 ± 2.2a 139.0 ± 1.6a
5 166.6 ± 6.4a 893.4 ± 53.4a 183.8 ± 12.0b 202.8 ± 7.2a
V max
0 (Control) 100.0 ± 3.2 100.0 ± 3.4 100.0 ± 2.1 100.0 ± 2.0
0.2 96.1 ± 2.9 105.0 ± 5.4 105.3 ± 2.5 102.4 ± 3.3
0.5 97.4 ± 2.6 112.6 ± 6.5 109.2 ± 2.2 102.2 ± 1.2
1 N.E. N.E. 96.6 ± 6.5 N.E.
2 114.6 ± 6.3 131.4 ± 9.4 101.9 ± 2.7 102.9 ± 3.1
5 124.5 ± 3.8b 96.9 ± 0.8 76.3 ± 3.3b 98.2 ± 3.3
CLint
0 (Control) 100.0 ± 4.6 100.0 ± 0.2 100.0 ± 4.3 100.0 ± 6.0
0.2 141.7 ± 7.7b 63.5 ± 1.4c 103.2 ± 1.9 82.6 ± 1.0
0.5 149.8 ± 9.5b 37.1 ± 0.4c 107.5 ± 2.2 79.4 ± 5.8
1 N.E. N.E. 103.4 ± 11.5 N.E.
2 86.8 ± 0.2b 25.9 ± 0.5c 77.0 ± 3.3b 74.0 ± 3.1b
5
74.7 ± 0.5b
10.9 ± 0.6c
41.5 ± 0.9a
48.4 ± 0.1a
  • N.E. = Not evaluated.

  • a Significantly different from control: P < 0.01, Student's t test.

  • b Significantly different from control: P < 0.05, Student's t test.

  • c Significantly different from control: P < 0.001, Student's t test.