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The In Vivo Effect ...
The In Vivo Effect of Transcellular Permeation Enhancers on the Intestinal Permeability of Two Peptide Drugs Enalaprilat and Hexarelin
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- Dahlgren, David (author)
- Uppsala universitet,Institutionen för farmaci
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- Sjöblom, Markus, 1973- (author)
- Uppsala universitet,Sjöblom/Nylander: Gastrointestinal fysiologi
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- Hedeland, Mikael (author)
- Uppsala universitet,Analytisk farmaceutisk kemi,Natl Vet Inst SVA, S-75189 Uppsala, Sweden.
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- Lennernäs, Hans (author)
- Uppsala universitet,Institutionen för farmaci
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(creator_code:org_t)
- 2020-01-26
- 2020
- English.
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In: Pharmaceutics. - : MDPI. - 1999-4923. ; 12:2
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Abstract
Subject headings
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- Permeation enhancers like sodium dodecyl sulfate (SDS) and caprate increase the intestinal permeability of small model peptide compounds, such as enalaprilat (349 Da). However, their effects remain to be investigated for larger low-permeability peptide drugs, such as hexarelin (887 Da). The objective of this single-pass perfusion study in rat was to investigate the effect of SDS at 5 mg/mL and of caprate administered at different luminal concentrations (5, 10, and 20 mg/mL) and pH (6.5 and 7.4). The small intestinal permeability of enalaprilat increased by 8- and 9-fold with SDS at 5 mg/mL and with caprate at 10 and 20 mg/mL but only at pH 7.4, where the free dissolved caprate concentration is higher than at pH 6.5 (5 vs. 2 mg/mL). Neither SDS nor caprate at any of the investigated luminal concentrations enhanced absorption of the larger peptide hexarelin. These results show that caprate requires doses above its saturation concentration (a reservoir suspension) to enhance absorption, most likely because dissolved caprate itself is rapidly absorbed. The absent effect on hexarelin may partly explain why the use of permeation enhancers for enabling oral peptide delivery has largely failed to evolve from in vitro evaluations into approved oral products. It is obvious that more innovative and effective drug delivery strategies are needed for this class of drugs.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
Keyword
- permeation enhancers
- absorption-modifying excipients
- oral peptide delivery
- intestinal permeability
- intestinal perfusion
- pharmaceutical development
Publication and Content Type
- ref (subject category)
- art (subject category)
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