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Research ArticleABSORPTION, DISTRIBUTION, METABOLISM, AND EXCRETION

Intranasal Delivery of Morphine

L. Illum, P. Watts, A. N. Fisher, M. Hinchcliffe, H. Norbury, I. Jabbal-Gill, R. Nankervis and S. S. Davis
Journal of Pharmacology and Experimental Therapeutics April 2002, 301 (1) 391-400; DOI: https://doi.org/10.1124/jpet.301.1.391
L. Illum
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P. Watts
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A. N. Fisher
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M. Hinchcliffe
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H. Norbury
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I. Jabbal-Gill
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R. Nankervis
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S. S. Davis
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Abstract

Morphine administered nasally to humans as a simple solution is only absorbed to a limited degree, with a bioavailability of the order of 10% compared with intravenous administration. This article describes the development of novel nasal morphine formulations based on chitosan, which, in the sheep model, provide a highly increased absorption with a 5- to 6-fold increase in bioavailability over simple morphine solutions. The chitosan-morphine nasal formulations have been tested in healthy volunteers in comparison with a slow i.v. infusion (over 30 min) of morphine. The results show that the nasal formulation was rapidly absorbed with a Tmax of 15 min or less and a bioavailability of nearly 60%. The shape of the plasma profile for nasal delivery of the chitosan-morphine formulation was similar to the one obtained for the slow i.v. administration of morphine. Furthermore, the metabolite profile obtained after the nasal administration of the chitosan-morphine nasal formulation was essentially identical to the one obtained for morphine administered by the intravenous route. The levels of both morphine-6-glucuronide and morphine-3-glucuronide were only about 25% of that found after oral administration of morphine. It is concluded that a properly designed nasal morphine formulation (such as one with chitosan) can result in a noninjectable opioid product capable of offering patients rapid and efficient pain relief.

Footnotes

  • All authors of this article are employees of West Pharmaceutical Services and as such have an indirect interest in the outcome of the research. The employees gain no direct financial benefit from this research apart from any benefit that may arise from the impact of the results on share prices. Some of the authors have shares or share options in the company.

  • Abbreviations:
    M-6-G
    morphine-6-glucuronide
    M-3-G
    morphine-3-glucuronide
    SMS
    starch microspheres
    LPC
    lysophosphatidylcholine
    HPLC
    high-performance liquid chromatography
    AUC
    area under the plasma curve
    F%
    bioavailability
    ANOVA
    analysis of variance
    • Received August 8, 2001.
    • Accepted December 24, 2001.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 301 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 301, Issue 1
1 Apr 2002
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Research ArticleABSORPTION, DISTRIBUTION, METABOLISM, AND EXCRETION

Intranasal Delivery of Morphine

L. Illum, P. Watts, A. N. Fisher, M. Hinchcliffe, H. Norbury, I. Jabbal-Gill, R. Nankervis and S. S. Davis
Journal of Pharmacology and Experimental Therapeutics April 1, 2002, 301 (1) 391-400; DOI: https://doi.org/10.1124/jpet.301.1.391

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Research ArticleABSORPTION, DISTRIBUTION, METABOLISM, AND EXCRETION

Intranasal Delivery of Morphine

L. Illum, P. Watts, A. N. Fisher, M. Hinchcliffe, H. Norbury, I. Jabbal-Gill, R. Nankervis and S. S. Davis
Journal of Pharmacology and Experimental Therapeutics April 1, 2002, 301 (1) 391-400; DOI: https://doi.org/10.1124/jpet.301.1.391
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  • Characterization of P-glycoprotein Inhibition by Major Cannabinoids from Marijuana
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