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P‐glycoprotein is not involved in the differential oral potency of naloxone and naltrexone
Author(s) -
Kanaan Mouna,
Daali Youssef,
Dayer Pierre,
Desmeules Jules
Publication year - 2009
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/j.1472-8206.2009.00724.x
Subject(s) - naltrexone , pharmacology , bioavailability , p glycoprotein , chemistry , (+) naloxone , efflux , opioid , antagonist , opioid receptor , morphine , transporter , receptor , medicine , biochemistry , multiple drug resistance , gene , antibiotics
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 μ m ) across the monolayers was investigated in the presence and absence of the specific P‐gp inhibitor GF120918 (4 μ m ). 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.