Why does the steady-state plasma concentration of a drug with high hepatic extraction ratio increase less than expected when a moderate CYP3A4 inhibitor is co-administered?

💡 Explanation

The steady-state concentration increase is blunted because hepatic drug clearance is dominated by blood flow, rather than CYP3A4 activity. Therefore, inhibiting CYP3A4 has limited impact; rather than a large increase, blood flow continues to clear the drug.

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