Oral and rectal nalbuphine bioavailability: first-pass metabolism in rats and dogs.
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.
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D004285:Dogs; D005260:Female; D007275:Injections, Intravenous; D007700:Kinetics; D008297:Male; D009019:Morphinans / Q000378:metabolism*; D009266:Nalbuphine / Q000008:administration & dosage / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012007:Rectum; D012459:Salicylates / Q000494:pharmacology; D013488:Suppositories
D009019:Morphinans; D012459:Salicylates; D013488:Suppositories; D009266:Nalbuphine