Oral absorption of D-oligopeptides in rats via the paracellular route

Yan Ling He, Susan Murby, Larry Gifford, Andrew Collett, Geoff Warhurst, Kenneth T. Douglas, Malcolm Rowland, John Ayrton

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Purpose. This study was undertaken to examine the structural determinants of oral bioavailability in the rat of a set of oligopeptides comprising D-amino acids, which were taken to be absorbed paracellularly based on a pronounced sensitivity of permeability to electrical resistance in Caco-2 cell monolayers. Methods. The study series comprised eleven D-oligopeptides, designed not to be recognised by peptidases or transport proteins, and to have molecular weights between 222 and 406 daltons with different net electrical charges and composition of D-amino acids. All the peptides were [3H]-radiolabelled and analyzed by HPLC with radiometric detection. Bioavailability was estimated based on 24-hr urinary excretion of unchanged peptide after oral and intravenous administrations. Results. As expected, the series proved metabolically stable. Bioavailability was independent of oral dose when varied by a factor of 10,000, suggesting passive absorption. Whereas bioavailability decreased sharply from 30% to 1% with increasing molecular weight, net charge showed little, if any, effect on bioavailability. Conclusions. This D-oligopeptide model series served as a useful probe for the structural requirements for paracellular absorption in vivo. A critical determinant of bioavailability is molecular size, expressed as molecular weight in this study; net charged appeared of much lesser importance.

Original languageEnglish
Pages (from-to)1673-1678
Number of pages6
JournalPharmaceutical Research
Volume13
Issue number11
DOIs
Publication statusPublished - 1 Nov 1996
Externally publishedYes

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Oligopeptides
Biological Availability
Rats
Molecular Weight
Molecular weight
Amino Acids
Peptides
Acoustic impedance
Caco-2 Cells
Electric Impedance
Intravenous Administration
Oral Administration
Monolayers
Permeability
Carrier Proteins
Peptide Hydrolases
High Pressure Liquid Chromatography
Chemical analysis

Cite this

He, Y. L., Murby, S., Gifford, L., Collett, A., Warhurst, G., Douglas, K. T., ... Ayrton, J. (1996). Oral absorption of D-oligopeptides in rats via the paracellular route. Pharmaceutical Research, 13(11), 1673-1678. https://doi.org/10.1023/A:1016440707092
He, Yan Ling ; Murby, Susan ; Gifford, Larry ; Collett, Andrew ; Warhurst, Geoff ; Douglas, Kenneth T. ; Rowland, Malcolm ; Ayrton, John. / Oral absorption of D-oligopeptides in rats via the paracellular route. In: Pharmaceutical Research. 1996 ; Vol. 13, No. 11. pp. 1673-1678.
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He, YL, Murby, S, Gifford, L, Collett, A, Warhurst, G, Douglas, KT, Rowland, M & Ayrton, J 1996, 'Oral absorption of D-oligopeptides in rats via the paracellular route', Pharmaceutical Research, vol. 13, no. 11, pp. 1673-1678. https://doi.org/10.1023/A:1016440707092

Oral absorption of D-oligopeptides in rats via the paracellular route. / He, Yan Ling; Murby, Susan; Gifford, Larry; Collett, Andrew; Warhurst, Geoff; Douglas, Kenneth T.; Rowland, Malcolm; Ayrton, John.

In: Pharmaceutical Research, Vol. 13, No. 11, 01.11.1996, p. 1673-1678.

Research output: Contribution to journalArticle

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T1 - Oral absorption of D-oligopeptides in rats via the paracellular route

AU - He, Yan Ling

AU - Murby, Susan

AU - Gifford, Larry

AU - Collett, Andrew

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AU - Douglas, Kenneth T.

AU - Rowland, Malcolm

AU - Ayrton, John

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