If a drug with high hepatic clearance is administered orally but its bioavailability is much lower than expected, which mechanism explains this discrepancy?

💡 Explanation

High hepatic clearance indicates the liver efficiently removes the drug. Extensive first-pass metabolism by the liver during oral absorption reduces the amount of drug reaching systemic circulation, because the drug is metabolized before it can exert its effects; therefore, bioavailability decreases substantially rather than the other options.

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