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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / antagonists & inhibitors
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / physiology*
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Acridines / pharmacology
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Administration, Oral
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Biological Availability
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Biological Transport
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Blotting, Western
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Caco-2 Cells
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Electric Impedance
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Humans
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Microscopy, Electron, Transmission
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Molecular Structure
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Naloxone / administration & dosage
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Naloxone / chemistry
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Naloxone / pharmacokinetics*
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Naltrexone / administration & dosage
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Naltrexone / chemistry
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Naltrexone / pharmacokinetics
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Narcotic Antagonists / administration & dosage
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Narcotic Antagonists / chemistry
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Narcotic Antagonists / pharmacokinetics*
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Tetrahydroisoquinolines / pharmacology
Substances
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ATP Binding Cassette Transporter, Subfamily B, Member 1
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Acridines
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Narcotic Antagonists
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Tetrahydroisoquinolines
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Naloxone
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Naltrexone
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Elacridar