Testosterone CYP3A4-dependent

Figure 13 Effect of substrate incubation time on the metabolism-dependent inhibition of CYP3A4/5 by mibefradil. Mibefradil (0.01 to 10 pM) was examined as a direct-acting and metabolism-dependent inhibitor with either a 0- or 15-minute preincubation with NADPH followed by either a 5- or 30-minute incubation with testosterone (100 pM). In both cases, the IC50 value after a 15-minute preincubation with NADPH was approximately 0.07 pM. However, the IC50 value for direct inhibition (0-minute preincubation) varied nearly fourfold depending on the length of the substrate incubation, with a longer substrate incubation period diminishing the apparent impact of metabolism-dependent inhibition due to increased inactivation during the substrate incubation.

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