Analysis of Structural Requirements for the Absorption of Drugs and Macromolecules from the Nasal Cavity

An octapeptide and a protein, of molecular weights 800 and 34 000, respectively, were found to have nasal bioavailabilities of 73 and 0.6%, respectively, in the rat. This data, combined with reported values for 23 other compounds, indicated good availability without adjuvants for all molecules up to...

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Bibliographic Details
Published in:Journal of pharmaceutical sciences 1987-07, Vol.76 (7), p.535-540
Main Authors: McMartin, Colin, Hutchinson, Lusie E.F., Hyde, Robert, Peters, Gill E.
Format: Article
Language:English
Subjects:
Absorption
Administration, Intranasal
Animals
Biological and medical sciences
Biological Availability
Biological Transport, Active
Cromolyn Sodium - administration & dosage
Cromolyn Sodium - pharmacokinetics
General pharmacology
Horseradish Peroxidase - administration & dosage
Horseradish Peroxidase - pharmacokinetics
Male
Medical sciences
Molecular Weight
Nasal Cavity - metabolism
Oligopeptides - administration & dosage
Oligopeptides - pharmacokinetics
Peptide Fragments - administration & dosage
Peptide Fragments - pharmacokinetics
Pharmaceutical Preparations - administration & dosage
Pharmacokinetics
Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions
Pharmacology. Drug treatments
Rats
Somatostatin - administration & dosage
Somatostatin - analogs & derivatives
Somatostatin - pharmacokinetics
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Summary:An octapeptide and a protein, of molecular weights 800 and 34 000, respectively, were found to have nasal bioavailabilities of 73 and 0.6%, respectively, in the rat. This data, combined with reported values for 23 other compounds, indicated good availability without adjuvants for all molecules up to 1000 molecular weight (mean 70%, SD between compounds 26%, n=15) with a decline in availability above this value. The relationship between absorption and molecular weight was modeled assuming competition between constant clearance from the nasal cavity and molecular weight-dependent transport through the mucosa. Deviations of absorption from values predicted by this model did not correlate with factors such as charge, hydrophobicity, or susceptibility to aminopeptidases, but the relative absorption of cyclic and cross-linked peptides and proteins was significantly greater than that of linear peptides. It is argued that the most likely route for transport is through junctions between cells and that surface-active adjuvants (MW 6000) which markedly enhance insulin uptake may act by rendering hydrophobic areas of contact of the junctional proteins temporarily hydrophilic. The nasal route is suitable for efficient, rapid delivery of many molecules of molecular weight
ISSN:0022-3549
1520-6017
DOI:10.1002/jps.2600760709