The 'first-pass effect' explains why oral morphine requires higher doses than IV morphine for equivalent analgesia. For a drug with oral bioavailability of 25%, to achieve the same systemic exposure as 10 mg IV, the oral dose required is:

• A 20 mg
• B 2.5 mg
• C 25 mg
• D 40 mg ✓

Explanation

Bioavailability (F) = 25% = 0.25 means only 25% of the oral dose reaches systemic circulation. To achieve the same exposure as 10 mg IV: oral dose = IV dose / F = 10 / 0.25 = 40 mg. Morphine undergoes extensive hepatic first-pass metabolism primarily to morphine-3-glucuronide (inactive) and morphine-6-glucuronide (active), resulting in oral bioavailability of approximately 25–35%. This is why standard oral morphine doses (e.g., 30 mg) are approximately 3× the IV dose (10 mg).

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

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Written and medically reviewed by the StethoPrep medical team.