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Direct Nose-to-Brain Transfer of Morphine After Nasal Administration to Rats

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Purpose

The aim of this study was to quantify the olfactory transfer of morphine to the brain hemispheres by comparing brain tissue and plasma morphine levels after nasal administration with those after intravenous administration.

Methods

Morphine (1.0 mg/kg body weight) was administered via the right nostril or intravenously as a 15-min constant-rate infusion to male rats. The content of morphine and its metabolite morphine-3-glucuronide in samples of the olfactory bulbs, brain hemispheres, and plasma was assessed using high-performance liquid chromatography, and the areas under the concentration–time curves (AUC) were calculated.

Results

At both 5 and 15 min after administration, brain hemisphere morphine concentrations after nasal administration were similar to those after i.v. administration of the same dose, despite lower plasma concentrations after nasal administration. The brain hemispheres/plasma morphine AUC ratios for the 0–5 min period were thus approximately 3 and 0.1 after nasal and i.v. administration, respectively, demonstrating a statistically significant early distribution advantage of morphine to the brain hemispheres via the nasal route.

Conclusion

Morphine is transferred via olfactory pathways to the brain hemispheres, and drug transfer via this route significantly contributes to the early high brain concentrations after nasal administration to rats.

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Abbreviations

CSF:

cerebrospinal fluid

HPLC:

high-performance liquid chromatography

LOB:

left olfactory bulb

M3G:

morphine-3-glucuronide

PBS:

phosphate-buffered saline

ROB:

right olfactory bulb

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Acknowledgments

The authors would like to thank Jessica Strömgren for excellent assistance with the animal experiments, and Britt Jansson for expert assistance with the HPLC system. The National Network of Drug Delivery (NNDD), part of the Swedish Foundation of Strategic Research, is acknowledged for financially supporting this work.

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Authors and Affiliations

  1. Department of Pharmacy, Uppsala University, P.O. Box 580, SE-751 23, Uppsala, Sweden

    Ulrika Espefält Westin, Johan Gråsjö & Erik Björk

  2. Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden

    Emma Boström & Margareta Hammarlund-Udenaes

Authors
  1. Ulrika Espefält Westin
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  2. Emma Boström
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  3. Johan Gråsjö
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  4. Margareta Hammarlund-Udenaes
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  5. Erik Björk
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Correspondence to Erik Björk.

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Westin, U.E., Boström, E., Gråsjö, J. et al. Direct Nose-to-Brain Transfer of Morphine After Nasal Administration to Rats. Pharm Res 23, 565–572 (2006). https://doi.org/10.1007/s11095-006-9534-z

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  • DOI: https://doi.org/10.1007/s11095-006-9534-z

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