TABLE 1

Effects of gefitinib on NPC and APC formations by CYP3A4 in human liver or small intestinal microsomes

The concentration of irinotecan was 20 μM. The control activities of NPC and APC formation from irinotecan by CYP3A4 in the liver microsomes or in the small intestinal microsomes determined in the absence of an inhibitor or an activator were 34.2 and 8.63 pmol/min/mg protein or 3.14 and 1.32 pmol/min/mg protein.

Chemical
Concentration
NPC Formationa
APC Formationa
μM % of control
Liver
    Gefitinib 40.0 30.8 ± 1.4b 173 ± 12b
    Ketoconazole 1.0 4.31 ± 0.35b 5.31 ± 1.2b
    Erythromycin 100.0 9.90 ± 1.2b 17.6 ± 2.8b
    α-Naphthoflavone 5.0 151 ± 12b 313 ± 12b
Small Intestine
    Gefitinib 40.0 70.4 ± 3.6b 252 ± 24b
    Ketoconazole 1.0 7.49 ± 0.92b 8.57 ± 0.23b
    Erythromycin 100.0 19.4 ± 1.9b 23.2 ± 4.5b
    α-Naphthoflavone
20.0
143 ± 4.0b
379 ± 16b

  • ↵ a Values are presented as mean ± S.D. (n = 3).

  • ↵ b Significant difference between values obtained in the presence or absence of an inhibitor or an activator (P < 0.05).