Bioavailability in vivo of naltrexone following transbuccal administration by an electronically-controlled intraoral device: A trial on pigs.

Libero Italo Giannola, Ada Maria Florena, Viviana De Caro, Giuseppina Campisi, Carlo Paderni, Andy Wolff, Thorsten Göttsche, Axel Schumacher

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Abstract

Naltrexone (NLX), an opioid antagonist, is widely used in the treatment of opiate addiction, alcoholism and smoking cessation. Its current peroral administration induces various adverse side effects and has limited efficacy since bioavailability and patient compliance are poor. The development of a long-acting drug delivery system of NLX may overcome the current drawbacks and help in the improvement of treatment of addiction. The primary endpoints of this study were: a) to compare the NLX bioavailability and pharmacokinetics after delivering a single transbuccal dose, released by a prototype of intraoral device, versus an intravenous (I.V.) bolus of the same drug dose; b) to verify the functioning of a prototype of a new intraoral device in vivo; c) to evaluate the permeation enhancement effect of iontophoresis; d) to assess any histomorphological changes in the buccal mucosa after transbuccal delivery. The system was tested on 6 pigs in a cross-over trial. Venous blood samples were drawn at a fixed timetable from the beginning of drug administration and analyzed for the presence of NLX, using an LC/MS/MS method. A punch biopsy was performed for histological analysis after the final experiment. The administration of I.V. NLX induced a sharp increase in blood levels after 5 min and then a steep decrease. In contrast, transmucosal delivery resulted in a gradual increase in blood NLX levels, reaching its peak after 90 min, followed by a slow decrease. After 6 h the blood levels of NLX delivered through the buccal mucosa were higher as compared to I.V. administration. No signs of flogosis or tissue damage were histologically highlighted. These results suggest that buccal delivery by an intraoral electronic device could potentially induce long-lasting, continuous and controlled blood levels of NLX, avoiding at the same time spikes of drug plasma levels typical of the I.V. administration route.
Lingua originaleEnglish
pagine (da-a)214-220
Numero di pagine7
RivistaJournal of Controlled Release
Volume145
Stato di pubblicazionePublished - 2010

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Naltrexone
Biological Availability
Swine
Equipment and Supplies
Intravenous Administration
Mouth Mucosa
Pharmaceutical Preparations
Opioid-Related Disorders
Iontophoresis
Narcotic Antagonists
Cheek
Smoking Cessation
Drug Delivery Systems
Patient Compliance
Cross-Over Studies
Alcoholism
Pharmacokinetics
Biopsy
Therapeutics

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

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title = "Bioavailability in vivo of naltrexone following transbuccal administration by an electronically-controlled intraoral device: A trial on pigs.",
abstract = "Naltrexone (NLX), an opioid antagonist, is widely used in the treatment of opiate addiction, alcoholism and smoking cessation. Its current peroral administration induces various adverse side effects and has limited efficacy since bioavailability and patient compliance are poor. The development of a long-acting drug delivery system of NLX may overcome the current drawbacks and help in the improvement of treatment of addiction. The primary endpoints of this study were: a) to compare the NLX bioavailability and pharmacokinetics after delivering a single transbuccal dose, released by a prototype of intraoral device, versus an intravenous (I.V.) bolus of the same drug dose; b) to verify the functioning of a prototype of a new intraoral device in vivo; c) to evaluate the permeation enhancement effect of iontophoresis; d) to assess any histomorphological changes in the buccal mucosa after transbuccal delivery. The system was tested on 6 pigs in a cross-over trial. Venous blood samples were drawn at a fixed timetable from the beginning of drug administration and analyzed for the presence of NLX, using an LC/MS/MS method. A punch biopsy was performed for histological analysis after the final experiment. The administration of I.V. NLX induced a sharp increase in blood levels after 5 min and then a steep decrease. In contrast, transmucosal delivery resulted in a gradual increase in blood NLX levels, reaching its peak after 90 min, followed by a slow decrease. After 6 h the blood levels of NLX delivered through the buccal mucosa were higher as compared to I.V. administration. No signs of flogosis or tissue damage were histologically highlighted. These results suggest that buccal delivery by an intraoral electronic device could potentially induce long-lasting, continuous and controlled blood levels of NLX, avoiding at the same time spikes of drug plasma levels typical of the I.V. administration route.",
author = "Giannola, {Libero Italo} and Florena, {Ada Maria} and {De Caro}, Viviana and Giuseppina Campisi and Carlo Paderni and Andy Wolff and Thorsten G{\"o}ttsche and Axel Schumacher",
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T1 - Bioavailability in vivo of naltrexone following transbuccal administration by an electronically-controlled intraoral device: A trial on pigs.

AU - Giannola, Libero Italo

AU - Florena, Ada Maria

AU - De Caro, Viviana

AU - Campisi, Giuseppina

AU - Paderni, Carlo

AU - Wolff, Andy

AU - Göttsche, Thorsten

AU - Schumacher, Axel

PY - 2010

Y1 - 2010

N2 - Naltrexone (NLX), an opioid antagonist, is widely used in the treatment of opiate addiction, alcoholism and smoking cessation. Its current peroral administration induces various adverse side effects and has limited efficacy since bioavailability and patient compliance are poor. The development of a long-acting drug delivery system of NLX may overcome the current drawbacks and help in the improvement of treatment of addiction. The primary endpoints of this study were: a) to compare the NLX bioavailability and pharmacokinetics after delivering a single transbuccal dose, released by a prototype of intraoral device, versus an intravenous (I.V.) bolus of the same drug dose; b) to verify the functioning of a prototype of a new intraoral device in vivo; c) to evaluate the permeation enhancement effect of iontophoresis; d) to assess any histomorphological changes in the buccal mucosa after transbuccal delivery. The system was tested on 6 pigs in a cross-over trial. Venous blood samples were drawn at a fixed timetable from the beginning of drug administration and analyzed for the presence of NLX, using an LC/MS/MS method. A punch biopsy was performed for histological analysis after the final experiment. The administration of I.V. NLX induced a sharp increase in blood levels after 5 min and then a steep decrease. In contrast, transmucosal delivery resulted in a gradual increase in blood NLX levels, reaching its peak after 90 min, followed by a slow decrease. After 6 h the blood levels of NLX delivered through the buccal mucosa were higher as compared to I.V. administration. No signs of flogosis or tissue damage were histologically highlighted. These results suggest that buccal delivery by an intraoral electronic device could potentially induce long-lasting, continuous and controlled blood levels of NLX, avoiding at the same time spikes of drug plasma levels typical of the I.V. administration route.

AB - Naltrexone (NLX), an opioid antagonist, is widely used in the treatment of opiate addiction, alcoholism and smoking cessation. Its current peroral administration induces various adverse side effects and has limited efficacy since bioavailability and patient compliance are poor. The development of a long-acting drug delivery system of NLX may overcome the current drawbacks and help in the improvement of treatment of addiction. The primary endpoints of this study were: a) to compare the NLX bioavailability and pharmacokinetics after delivering a single transbuccal dose, released by a prototype of intraoral device, versus an intravenous (I.V.) bolus of the same drug dose; b) to verify the functioning of a prototype of a new intraoral device in vivo; c) to evaluate the permeation enhancement effect of iontophoresis; d) to assess any histomorphological changes in the buccal mucosa after transbuccal delivery. The system was tested on 6 pigs in a cross-over trial. Venous blood samples were drawn at a fixed timetable from the beginning of drug administration and analyzed for the presence of NLX, using an LC/MS/MS method. A punch biopsy was performed for histological analysis after the final experiment. The administration of I.V. NLX induced a sharp increase in blood levels after 5 min and then a steep decrease. In contrast, transmucosal delivery resulted in a gradual increase in blood NLX levels, reaching its peak after 90 min, followed by a slow decrease. After 6 h the blood levels of NLX delivered through the buccal mucosa were higher as compared to I.V. administration. No signs of flogosis or tissue damage were histologically highlighted. These results suggest that buccal delivery by an intraoral electronic device could potentially induce long-lasting, continuous and controlled blood levels of NLX, avoiding at the same time spikes of drug plasma levels typical of the I.V. administration route.

UR - http://hdl.handle.net/10447/50519

UR - http://www.elsevier.com/ locate/jconrel

M3 - Article

VL - 145

SP - 214

EP - 220

JO - Journal of Controlled Release

JF - Journal of Controlled Release

SN - 0168-3659

ER -