Scientific article

P-glycoprotein is not involved in the differential oral potency of naloxone and naltrexone

Published inFundamental & clinical pharmacology, vol. 23, no. 5, p. 543-548
Publication date2009

The poor oral bioavailability of the opioid receptor antagonist naloxone (NA) when compared with naltrexone (NX) may be related to a greater interaction of naloxone with the efflux drug transporter P-glycoprotein (P-gp). We studied the involvement of P-gp in the transepithelial transport of the two opioid receptor antagonists, using a validated human in vitro Caco-2 cell monolayer model. The bidirectional transport of NA and NX (1, 50 and 100 microm) across the monolayers was investigated in the presence and absence of the specific P-gp inhibitor GF120918 (4 microm). NA and NX showed equal transport rates between the apical-to-basolateral (A-B) and the basolateral-to-apical (B-A) directions and neither the influx nor the efflux transport was affected by the P-gp inhibitor (P > 0.05). In conclusion, NA and NX are not P-gp substrates. The differential oral bioavailability of the two opioid antagonists is P-gp independent.

  • Acridines/pharmacology
  • Administration, Oral
  • Biological Availability
  • Biological Transport
  • Blotting, Western
  • Caco-2 Cells
  • Electric Impedance
  • Humans
  • Microscopy, Electron, Transmission
  • Molecular Structure
  • Naloxone/administration & dosage/chemistry/pharmacokinetics
  • Naltrexone/administration & dosage/chemistry/pharmacokinetics
  • Narcotic Antagonists/administration & dosage/chemistry/pharmacokinetics
  • P-Glycoprotein/antagonists & inhibitors/metabolism/physiology
  • Tetrahydroisoquinolines/pharmacology
Citation (ISO format)
KANAAN, Mouna et al. P-glycoprotein is not involved in the differential oral potency of naloxone and naltrexone. In: Fundamental & clinical pharmacology, 2009, vol. 23, n° 5, p. 543–548. doi: 10.1111/j.1472-8206.2009.00724.x
Main files (1)
Article (Published version)
ISSN of the journal0767-3981

Technical informations

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