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Table 4 Kinetic parameters for metabolic enzymes.

From: Drug interaction prediction using ontology-driven hypothetical assertion framework for pathway generation followed by numerical simulation

Enzyme Substrate Product K m [μ M] V max [pmol/min/mg protein] α[mg protein/g tissue] V max ·α/K m [mL/min/g tissue]
Carboxylesterase Irinotecan SN-38 2.30 2.11 128 0.117
Carboxylesterase NPC SN-38 2.30 2.11 128 0.117
CYP3A4 Irinotecan APC 18.4 26.0 73.3 0.104
CYP3A4 Irinotecan NPC 48.2 74.1 11.7 0.0180
UGT1A1 SN-38 SN-38G 3.80 50.8 750 10.0
CYP3A4 KCZ MOK 0.00810 12.5 44.3 68.4
  1. Because of the lack of experimental data, K m and V max values for metabolism of NPC to SN-38 by CE were assumed to be the same as those for metabolism of irinotecan to SN-38 by CE. K m and V max values for other reactions were obtained from the published papers [25–29]. Values of unknown parameter α were determined so that the simulation concentration/time profile fit to the experimental data published by Slatter et al. [18]. The relatively high fitted value for α in the glucronidation of SN-38 may result from the increase in UGT1A1 expression as drug response. The relatively low value for α in the oxidation of irinotecan to NPC by CYP3A4 suggests a competition in this reaction with the oxidation of irinotecan to APC by CYP3A4.