Dose-dependent naloxone-induced morphine withdrawal symptoms in opioid-dependent males-a double-blinded, randomized study.
morphine
naloxone
opioid maintenance treatment
opioid withdrawal syndrome
substance abuse-intravenous
Journal
British journal of clinical pharmacology
ISSN: 1365-2125
Titre abrégé: Br J Clin Pharmacol
Pays: England
ID NLM: 7503323
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
received:
11
06
2019
revised:
01
11
2019
accepted:
26
02
2020
pubmed:
8
3
2020
medline:
3
7
2021
entrez:
8
3
2020
Statut:
ppublish
Résumé
Oral opioid preparations combined with naloxone are intended to induce a transient acute withdrawal syndrome to avoid intravenous misuse. This trial aimed to establish an appropriate morphine-naloxone dose ratio for an abuse-deterrent oral opioid formulation. In a randomized, double-blinded, 2 × 2 cross-over trial, 43 patients with opioid use disorder were challenged with intravenous morphine HCl Ph.Eur. (75 mg; [morphine mono]) or morphine HCl Ph.Eur. and naloxone HCl Ph.Eur. at ratios of 100:1 (75 mg: 0.75 mg; [morphine-naloxone 100:1]) or 200:1 (75 mg: 0.375 mg; [morphine-naloxone 200:1]). Acute naloxone-induced opioid withdrawal was evaluated using subjective (Short Opiate Withdrawal Scale-German [SOWS-G]) and observer-rated (Objective Opiate Withdrawal Scale [OOWS], Wang scale) questionnaires, and physiological parameters. For statistical analysis, the area under the curve between baseline and 20 minutes after drug administration of the outcome variables was calculated. Intravenous morphine-naloxone caused rapid withdrawal symptoms. Coadministration of naloxone dose-dependently (morphine-naloxone 100:1 > morphine-naloxone 200:1) increased SOWS-G, OOWS and Wang Scale area under the curve when compared to morphine mono, respectively (all P < .0001). A similar response was detectable for changes of pupil diameter. Blood pressure and respiratory rate changed heterogeneously, and heart rate was unaltered by morphine without or with naloxone. Morphine-naloxone 100:1 effectively suppresses the pleasurable effects of intravenous morphine and results in an aversive withdrawal reaction. A lower naloxone concentration as used in morphine-naloxone 200:1 does not appear to be appropriate to prevent intravenous morphine misuse.
Identifiants
pubmed: 32145041
doi: 10.1111/bcp.14271
pmc: PMC7373709
doi:
Substances chimiques
Analgesics, Opioid
0
Narcotic Antagonists
0
Naloxone
36B82AMQ7N
Morphine
76I7G6D29C
Types de publication
Journal Article
Randomized Controlled Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
1610-1619Informations de copyright
© 2020 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.
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