title: P-glycoprotein is not involved in the differential oral potency of naloxone and naltrexone.
abstract: 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.
authors: Clinical Pharmacology, Geneva University Hospitals, Faculty of Medicine, University of Geneva, CH-1211 Geneva 14, Switzerland.
authors: Mouna
authors: M
authors: Kanaan
authors: Youssef
authors: Y
authors: Daali
authors: Pierre
authors: P
authors: Dayer
authors: Jules
authors: J
authors: Desmeules
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D000166:Acridines / Q000494:pharmacology; D000284:Administration, Oral; D001682:Biological Availability; D001692:Biological Transport; D015153:Blotting, Western; D018938:Caco-2 Cells; D017097:Electric Impedance; D006801:Humans; D046529:Microscopy, Electron, Transmission; D015394:Molecular Structure; D009270:Naloxone / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D009271:Naltrexone / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D044005:Tetrahydroisoquinolines / Q000494:pharmacology
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000166:Acridines; D009292:Narcotic Antagonists; D044005:Tetrahydroisoquinolines; D009270:Naloxone; D009271:Naltrexone; C083501:Elacridar