Oral and rectal nalbuphine bioavailability: First‐pass metabolism in rats and dogs

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Abstract
The disposition of the narcotic antagonist/analgesic nalbuphine after i.v., oral, and rectal dosing was evaluated in rats and dogs. In both species nalbuphine had high systemic clearance and low oral bioavailability as a result of extensive first‐pass metabolism. Administration to a closed 2 cm length of rectum in rats resulted in complete bioavailability; first‐pass metabolism was circumvented. However, the extent of first‐pass metabolism increased when the dose was not restricted to the lower rectum. Rectal nalbuphine bioavailability in dogs from a solution or three suppository formulations was low and equivalent to oral bioavailability. This was probably because of upward spreading of the dose and subsequent first‐pass metabolism. Sodium salicylate, which has been shown to improve rectal absorption of other drugs, did not affect nalbuphine bioavailability rectally.