Transdermal delivery of a buprenorphine/naltrexone combination for the treatment of polydrug abuse

Research output: Contribution to journalMeeting abstract

Abstract

Background and Aim:
There is evidence that a buprenorphine/naltrexone combination may be effective as a relapse prevention not only for opioid abuse, but for polydrug abuse, yet little work has been carried out to determine the optimum ratio of the two drugs. A significant problem with this treatment strategy arises from the fact that buprenorphine and naltrexone need to be administered by different routes. However, both buprenorphine and naltrexone can be delivered transdermally using iontophoresis, and we are cur-rently using this technique to develop a buprenor-phine/naltrexone combination therapy that is effective in reducing relapse to polydrug abuse.

Method:
Using conditioned place preference (CPP) in male Sprague-Dawley rats, the rewarding properties of buprenorphine and naltrexone combinations were assessed. The ability of buprenorphine/naltrexone to inhibit drug-primed reinstatement of morphine-induced CPP was then tested.

Results:
Buprenorphine alone (0.3 mg/kg) was rewarding, whereas a buprenorphine to naltrexone ratio of 1:10 (0.3 and 3 mg/kg) was aversive. However, a ratio of 1:3 (0.3 and 1 mg/kg) was neither rewarding nor aversive. A morphine priming dose of 2.5 mg/kg reinstated morphine CPP (animals were trained to demonstrate CPP with 10 mg/kg morphine followed by extinction training), an effect that was inhibited by prior administration of buprenorphine/naltrexone (0.3 and 1 mg/kg respectively). All drugs were administered ip

Conclusions:
We have demonstrated a combination of buprenorphine/naltrexone with no rewarding or aversive effects that appears to inhibit reinstatement in an animal model of drug-seeking behavior. Ongoing work is designed to further test the ability of buprenorphine/naltrexone to prevent CPP reinstatement, and to optimise conditions for their transdermal delivery.
LanguageEnglish
Pages257
Number of pages1
JournalPharmacological Reports
Volume63
Issue number1
DOIs
StatusPublished - Jan 2011
EventEuropean Opioid Conference 2011 - Krakow, Poland
Duration: 1 Jan 2011 → …

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Buprenorphine
Naltrexone
Morphine
Therapeutics
Aptitude
Drug-Seeking Behavior
Pharmaceutical Preparations
Iontophoresis
Secondary Prevention
Opioid Analgesics
Sprague Dawley Rats
Animal Models
Recurrence

Cite this

@article{1983f847b77f492792435376f4a5076b,
title = "Transdermal delivery of a buprenorphine/naltrexone combination for the treatment of polydrug abuse",
abstract = "Background and Aim:There is evidence that a buprenorphine/naltrexone combination may be effective as a relapse prevention not only for opioid abuse, but for polydrug abuse, yet little work has been carried out to determine the optimum ratio of the two drugs. A significant problem with this treatment strategy arises from the fact that buprenorphine and naltrexone need to be administered by different routes. However, both buprenorphine and naltrexone can be delivered transdermally using iontophoresis, and we are cur-rently using this technique to develop a buprenor-phine/naltrexone combination therapy that is effective in reducing relapse to polydrug abuse.Method:Using conditioned place preference (CPP) in male Sprague-Dawley rats, the rewarding properties of buprenorphine and naltrexone combinations were assessed. The ability of buprenorphine/naltrexone to inhibit drug-primed reinstatement of morphine-induced CPP was then tested.Results:Buprenorphine alone (0.3 mg/kg) was rewarding, whereas a buprenorphine to naltrexone ratio of 1:10 (0.3 and 3 mg/kg) was aversive. However, a ratio of 1:3 (0.3 and 1 mg/kg) was neither rewarding nor aversive. A morphine priming dose of 2.5 mg/kg reinstated morphine CPP (animals were trained to demonstrate CPP with 10 mg/kg morphine followed by extinction training), an effect that was inhibited by prior administration of buprenorphine/naltrexone (0.3 and 1 mg/kg respectively). All drugs were administered ipConclusions:We have demonstrated a combination of buprenorphine/naltrexone with no rewarding or aversive effects that appears to inhibit reinstatement in an animal model of drug-seeking behavior. Ongoing work is designed to further test the ability of buprenorphine/naltrexone to prevent CPP reinstatement, and to optimise conditions for their transdermal delivery.",
author = "Alistair Taverner and Sarah Cordery and Husbands, {Stephen M.} and Guy, {Richard H.} and Delgado-Charro, {Begona M.} and Bailey, {Christopher P.}",
year = "2011",
month = "1",
doi = "10.1016/S1734-1140(11)70484-4",
language = "English",
volume = "63",
pages = "257",
journal = "Pharmacological Reports",
issn = "1734-1140",
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T1 - Transdermal delivery of a buprenorphine/naltrexone combination for the treatment of polydrug abuse

AU - Taverner,Alistair

AU - Cordery,Sarah

AU - Husbands,Stephen M.

AU - Guy,Richard H.

AU - Delgado-Charro,Begona M.

AU - Bailey,Christopher P.

PY - 2011/1

Y1 - 2011/1

N2 - Background and Aim:There is evidence that a buprenorphine/naltrexone combination may be effective as a relapse prevention not only for opioid abuse, but for polydrug abuse, yet little work has been carried out to determine the optimum ratio of the two drugs. A significant problem with this treatment strategy arises from the fact that buprenorphine and naltrexone need to be administered by different routes. However, both buprenorphine and naltrexone can be delivered transdermally using iontophoresis, and we are cur-rently using this technique to develop a buprenor-phine/naltrexone combination therapy that is effective in reducing relapse to polydrug abuse.Method:Using conditioned place preference (CPP) in male Sprague-Dawley rats, the rewarding properties of buprenorphine and naltrexone combinations were assessed. The ability of buprenorphine/naltrexone to inhibit drug-primed reinstatement of morphine-induced CPP was then tested.Results:Buprenorphine alone (0.3 mg/kg) was rewarding, whereas a buprenorphine to naltrexone ratio of 1:10 (0.3 and 3 mg/kg) was aversive. However, a ratio of 1:3 (0.3 and 1 mg/kg) was neither rewarding nor aversive. A morphine priming dose of 2.5 mg/kg reinstated morphine CPP (animals were trained to demonstrate CPP with 10 mg/kg morphine followed by extinction training), an effect that was inhibited by prior administration of buprenorphine/naltrexone (0.3 and 1 mg/kg respectively). All drugs were administered ipConclusions:We have demonstrated a combination of buprenorphine/naltrexone with no rewarding or aversive effects that appears to inhibit reinstatement in an animal model of drug-seeking behavior. Ongoing work is designed to further test the ability of buprenorphine/naltrexone to prevent CPP reinstatement, and to optimise conditions for their transdermal delivery.

AB - Background and Aim:There is evidence that a buprenorphine/naltrexone combination may be effective as a relapse prevention not only for opioid abuse, but for polydrug abuse, yet little work has been carried out to determine the optimum ratio of the two drugs. A significant problem with this treatment strategy arises from the fact that buprenorphine and naltrexone need to be administered by different routes. However, both buprenorphine and naltrexone can be delivered transdermally using iontophoresis, and we are cur-rently using this technique to develop a buprenor-phine/naltrexone combination therapy that is effective in reducing relapse to polydrug abuse.Method:Using conditioned place preference (CPP) in male Sprague-Dawley rats, the rewarding properties of buprenorphine and naltrexone combinations were assessed. The ability of buprenorphine/naltrexone to inhibit drug-primed reinstatement of morphine-induced CPP was then tested.Results:Buprenorphine alone (0.3 mg/kg) was rewarding, whereas a buprenorphine to naltrexone ratio of 1:10 (0.3 and 3 mg/kg) was aversive. However, a ratio of 1:3 (0.3 and 1 mg/kg) was neither rewarding nor aversive. A morphine priming dose of 2.5 mg/kg reinstated morphine CPP (animals were trained to demonstrate CPP with 10 mg/kg morphine followed by extinction training), an effect that was inhibited by prior administration of buprenorphine/naltrexone (0.3 and 1 mg/kg respectively). All drugs were administered ipConclusions:We have demonstrated a combination of buprenorphine/naltrexone with no rewarding or aversive effects that appears to inhibit reinstatement in an animal model of drug-seeking behavior. Ongoing work is designed to further test the ability of buprenorphine/naltrexone to prevent CPP reinstatement, and to optimise conditions for their transdermal delivery.

UR - http://dx.doi.org/10.1016/S1734-1140(11)70484-4

U2 - 10.1016/S1734-1140(11)70484-4

DO - 10.1016/S1734-1140(11)70484-4

M3 - Meeting abstract

VL - 63

SP - 257

JO - Pharmacological Reports

T2 - Pharmacological Reports

JF - Pharmacological Reports

SN - 1734-1140

IS - 1

ER -