Buprenorphine Therapy of Opiate Addiction

156 Pages·2002·2.748 MB·English

by  Pierre Marquet (auth.), Pascal Kintz PharmD, PhD, Pierre Marquet MD, PhD (eds.)

Buprenorphine Therapy
of Opiate Addiction
F 0 REN S I e
SCIENCE MEDICINE
AND
Steven B. Kareh, MD, SERIES EDITOR
BUPRENORPHINE THERAPY OF OPIATE ADDICTION, edited by Pascal Kintz
and Pierre Marquet, 2002
ON-SITE DRUG TESTING, edited by Amanda l. lenkins
and Bruce A. Goldberger, 2002
BENZODIAZEPINES AND GHB: DETECTloN AND PHARMACOLOGY,
edited by Salvatore l. Salamone, 2002
TOXICOLOGY AND CLiNICAL PHARMACOLOGY OF HERBAL PRODUCTS,
ed ited by Melanie lohns Cupp, 2000
CRIMINAL POISONING: INVESTICATIONAL CUIDE FOR LAW ENFORCEMENT,
TOXICOLOCISTS, FORENSIC SCiENTISTS, ANO A TTORNEYS,
by lohn H. Trestrail, 111, 2000
A PHYSICIAN'S GUIDE TO CLiNICAL FORENSIC MEDICINE,
ed ited by Margaret M. Stark, 2000
BRAIN IMAGING IN SUBSTANCE ABUSE: REsEARCH, CLiNICAL, AND FORENSIC ApPLICATIONS,
edited by Marc l. Kaufman, 2000
BUPRENORPHINE
THERAPY OF
OPIATE AOOICTION
Edited by
Pascal Kintz, PharmD, PhD
Institute of Legal Medicine, strasbourg, France
President, societe Fram;aise de Toxicologie Analytique
Pierre Marquet, MD, PhD
Department of Pharmacology and Toxicology, University Hospital;
Professor of Pharmacology, Faculty of Medicine, Limoges University, Limoges, France
Foreword by
Albert D. Fraser
Clinical and Forensie Toxicologist, Queen Elizabeth 11 Health Seien ces Centre and
Professor of Pathology and Pharmacy, Dalhousie University, Halifax, Nova scotia,
Canada; President, International Association for Therapeutic Drug Monitoring
and Clinical Toxicology, 2001-2003
~
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Library of Congress Cataloging in Publication Data
Buprenorphine therapy of opiate addiction 1 edited by Pascal Kintz, PierreMarquet; foreword by AlanD. Fraser.
p.; cm.
Includes bibliographical references and index.
ISBN 978-1-4684-9713-7 ISBN 978-1-59259-282-1 (eBook)
DOI 10.1007/978-1-59259-282-1
I. Opioid habit--Chemotherapy. 2. Buprenorphine. I. Kintz, Pascal. 11. Marquet, Pierre.
[DNLM: I. Buprenorphine--pharmacology. 2. Buprenorphine--therapeutic use. 3. Opioid-Related Dis
orders--drug therapy. QV 92 B9447 2002J
RC568.045 B87 2002
616.86'32061--de21
2001039718
Foreword
It is a great pleasure to write a foreword to this new book on buprenor
phine treatment in opiate dependency. Abuse of heroin is a major public health
problem worldwide. In the Uni ted States alone, there are almost one million
long-term users ofheroin. Clinical-and laboratory-based investigators in many
centers in France have written the largest number of chapters in this book.
This is because French physicians and scientists have the most experience
with high-dose buprenorphine treatment in opiate dependency. The experience
and contributions of the French in both c1inical- and laboratory-based studies
provide a wealth of knowledge for other opiate treatment centers having less
experience using buprenorphine. When one speaks about opiate dependency,
one is primarily referring to heroin addiction, although addiction to many other
opioids is a problem in various parts of the world. The first chapter discusses
the important fundamental question whether substituting heroin for a surrogate
opioid (such as methadone or buprenorphine) is a therapeutic treatment or
meant to serve another purpose in society. In another chapter, long-term main
tenance of opiate-dependent patients with high-dose buprenorphine
is compared to methadone use. This is important information because of the
significant differences between methadone and high-dose buprenorphine
as maintenance therapies. There are major differences in the frequency of
administration and delivery of buprenorphine compared to methadone
today. Two chapters present how buprenorphine is currently prescribed and
monitored in France and Australia.
Administration and monitoring of buprenorphine presents a great
challenge in specific populations. Two chapters in this book describe the use
of buprenorphine in the pregnant addict. The c1inical and/or forensic labora
tory plays an integral role in the assessment and monitoring of opiate-addicted
v
vi Foreword
patients since methadone was introduced clinically almost 40 years ago. The
latest advances in analytical techniques for the determination ofbuprenorphine
and metabolites in biological fluids and tissues are presented in another chapter.
Analytical methods developed in toxicology laboratories and the interpretation
of results are essential components of successful opiate addiction treatment
programs. Diversion of surrogate opioids such as buprenorphine and the
possibility of overdose/poisoning are always a concern. A chapter on
buprenorphine poisoning is an important feature of Buprenorpine Therapy
01 Opiate Addiction.
A reference text on high-dose buprenorphine in the treatment of opioid
addiction must cover all the key topics that treatment personnel and labora
tory scientists in this field experience in their working environment. The broad
scope and depth of topics covered by internationally known scientist and
physician authors will make this book a valuable reference text for individuals
working in the addiction field worldwide for many years.
Albert D. fraser
Halifax, Nova Scotia
Canada
Preface
Buprenorphine is a semisynthetic opioid derivative, closely related to
morphine and obtained from thebaine after a seven-step chemical procedure.
At low doses, buprenorphine is a powerful analgesic, 25 -40 times more potent
than morphine, with mixed agonist/antagonist activity on opioid receptors.
The drug is a partial Jl receptor agonist and a K receptor antagonist. It shows
very slow dissociation from opiate receptors, which is one of the reasons for
its long duration of action.
Buprenorphine is characterized by a weak oral bioavailability and, owing to
its high lipid solubility, by low therapeutic concentrations.
Under the tradename Temgesic® at dosages of 0.2 mg, buprenorphine
has been widely prescribed for about 20 years for the treatment of moderate
to severe pain as weIl as in anesthesiology for premedication and/or anes
thetic induction.
More recently, it also has been recognized as a medication of interest
for the substitutive management of opiate-dependent individuals. Under the
tradename Subutex®, a high-dosage formulation (0.4-, 2-, and 8-mg tablets
for sublingual use) has been available in France since February 1996 in this
specific indication. Today, this drug is largely used in France for the treat
ment of about 70,000 heroin addicts but can also be easily found on the
black market.
The fatality risks incurred by the misuse of buprenorphine seem to arise
through a combination of two practices: (1) association with other psycho
tropics, especially benzodiazepines and neuroleptics, and (2) improper use of
the tablet form for intravenous administration or massive oral doses.
Special thanks must go to all the authors who accepted our request to
write a chapter of what, we hope, is a worthwhile contribution to the literature.
It was our intention to cover both theoretical and practical aspects of
buprenorphine therapy in order to provide a reference book. As will be seen
vii
viii Preface
by the readers, pharmacology, controlled studies, clinical observations and
experience, drug delivery, analytical challenges and postmortem forensic toxi
cology were reviewed by the different authors. We believe these chapters will
provide readers not only with a comprehensive and well-documented survey
of what other investigators have reported, but also with each author's critical
evaluation of current knowledge in each of the areas surveyed.
Pascal Kintz,
PharmD, PhD
Pierre Marquet,
MD, PhD
Contents
Foreword by Albert D. Fraser .............................................................. v
Preface .................................................................................................. vii
Contributors ......................................................................................... xv
CHAPTER 1
Pharmacology of High-Dose Buprenorphine
Pierre Marquet ........................................................................................... 1
1. Introduction .......................................................................................................... 1
2. Pharmacokinetic Properties ................................................................................. 1
2.1. Absorption and Bioavai1abi1ity ................................................................... 1
2.2. Distribution .................................................................................................. 3
2.3. Metabolism ................................................................................................... 5
2.4. Excretion ...................................................................................................... 5
3. Pharmacodynamic Properties .............................................................................. 5
4. Administration Schedules .................................................................................... 8
5. Clinica1 Effects of Buprenorphine ...................................................................... 8
6. Conclusion ........................................................................................................... 9
References ................................................................................................................ 9
CHAPTER 2
Controlled Drug Administration Studies
of High-Dose Buprenorphine in Humans
Marilyn A. Huestis .................................................................................. 13
1. Introduction ........................................................................................................ 13
2. Bioavailabi1ity .................................................................................................... 14
3. Dose-Effect Profiles .......................................................................................... 16
4. Abuse Liability .................................................................................................. 16
5. Toxicity .............................................................................................................. 19
6. Safety and Abuse Liability of High-Dose Intravenous Buprenorphine .......... 21
7. ConcIusion ......................................................................................................... 23
References .............................................................................................................. 24
ix
x Contents
CHAPTER 3
High-Dose Buprenorphine for Treatment of Opioid Dependence
Eric C. Strain ........................................................................................... 29
1. Introduction ........................................................................................................ 29
2. Buprenorphine Solution vs Tablets ................................................................... 30
3. Effieaey of Buprenorphine vs Placebo: Clinical Trials ................................... 31
3.1. Summary of Plaeebo-Controlled Studies .................................................. 34
4. Effieaey of Buprenorphine vs Other Medieations:
Clinical Trials .................................................................................................... 34
4.1. Summary of Studies Comparing Buprenorphine
to Other Medieations ................................................................................. 44
5. Safety and Side Effeets of Buprenorphine ....................................................... 44
6. Summary and Conc1usions ................................................................................ 45
Aeknowledgment ................................................................................................... 47
Referenees .............................................................................................................. 47
CHAPTER 4
Foreseeable Advantages and Limits
of Buprenorphine-Naloxone Association
Michel Mallaret, Maurice Dematteis, Celine Villier,
Claude Elisabeth Barjhoux, and Chantal Gatignol .................... 51
1. Introduetion ........................................................................................................ 51
2. Advantages of Buprenorphine-Naloxone Assoeiation ..................................... 52
2.1. Advantages of Opiate-Naloxone Assoeiation: Lessons of the Past ......... 52
2.1.1. Epidemie of Pentazoeine and Tripelennamine Abuse
in the United States ......................................................................... 52
2.1.2. Epidemie of Analgesie Buprenorphine Abuse in New Zealand ... 53
2.2. Buprenorphine and Naloxone:
A Complex and Controversial Pharmacology .......................................... 53
2.3. Clinical Aspeets ......................................................................................... 54
2.3.1. Pharmaeokinetie/Pharmaeodynamie Advantages
of Assoeiated Naloxone in BupNx Combination .......................... 54
2.3.2. Sublingual Naloxone in BupNx Tablets Does Not Deerease
Buprenorphine Effeets .................................................................... 55
2.3.3. Sublingual Naloxone in BupNx Tablets Does Not Deerease
Blockade Effeets of Buprenorphine
in Opioid-Dependent Patients ........................................................ 55
2.3.4. Sublingual Naloxone in BupNx Tablets Does Not Preeipitate
Withdrawal Symptoms in Opioid-Dependent Patients ................. 56
2.3.5. Is the BupNx Combination Effeetive for Detoxifieation
or Treatment of Depressive Symptoms
in Opioid-Dependent Patients? ........................................................ 56