The equianalgesic oral dose of morphine is approximately three times its parenteral dose. The pharmacokinetic reason for this difference is:

• A Extensive first-pass glucuronidation in liver and gut wall limiting oral bioavailability to about 30 percent ✓
• B Active tubular secretion of morphine into urine after oral dosing
• C Saturation of mu receptors at parenteral doses requiring higher oral doses
• D Enterohepatic cycling that inactivates orally administered morphine

Explanation

Morphine undergoes extensive first-pass conjugation, mainly by UGT2B7 to morphine-3-glucuronide, in the intestinal wall and liver, leaving oral bioavailability around 25 to 35 percent. Hence the oral dose must be roughly three times the parenteral dose for equal analgesia. Receptor saturation is a pharmacodynamic concept and does not explain route-dependent dosing differences, which kills option C.

Reference: Katzung's Basic and Clinical Pharmacology, 15th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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