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Effects of absorpti...
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Roos, CarlUppsala universitet,Institutionen för farmaci
(author)
Effects of absorption-modifying excipients on jejunal drug absorption in simulated fasted and fed luminal conditions
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Numbers
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LIBRIS-ID:oai:DiVA.org:uu-363192
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-363192URI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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The pharmaceutical industry, prescribers, and patients have all traditionally preferred oral administration of drug products. In recent years there has been an increase in drug candidates with low solubility and/or low permeability, which may limit the use of oral administration. To increase the possibility of oral administration for the poorly permeating drugs, the use of absorption modifying excipients (AMEs) has been proposed, with the aim of increasing the fraction of dose absorbed. The effects of AMEs have previously been investigated in various animal models, including the single-pass intestinal perfusion (SPIP) in rats. To further improve the biorelevance and the in vivo predictiveness of the SPIP model, four compounds (atenolol, enalaprilat, ketoprofen, metoprolol) were perfused in fasted or fed state simulated intestinal fluid (FaSSIF or FeSSIF) together with the AMEs N-acetyl-cysteine, caprate, or sodium dodecyl sulphate. For the poorly permeating compounds enalaprilat and atenolol, the flux was increased the most by the addition of SDS in both FaSSIF and FeSSIF. For ketoprofen, the flux decreased in the presence of all AMEs in at least one of the perfusion media. The flux of metoprolol was not affected by any of the excipients. The changes in magnitude in the compounds’ absorptions were in general smaller in FeSSIF than in FaSSIF, possibly due to differences in colloidal structures present in FeSSIF that made the AMEs less available. The results in FeSSIF were similar to those from bolus-dosing in rat, which further suggests that the effect of AMEs on permeability is strongly affected by interactions between AMEs and colloidal structures in the intestinal lumen. The results suggest that, when investigating the effects of AMEs, the biorelevance of the SPIP method can be increased by the addition of intraluminal constituents to the perfusate.
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Dahlgren, DavidUppsala universitet,Institutionen för farmaci(Swepub:uu)davda219
(author)
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Sjögren, Erik,1977-Uppsala universitet,Institutionen för farmaci(Swepub:uu)ersjo473
(author)
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Sjöblom, Markus,1973-Uppsala universitet,Fysiologi(Swepub:uu)msj20812
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Hedeland, MikaelUppsala universitet,Analytisk vetenskap(Swepub:uu)mikahede
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Lennernäs, HansUppsala universitet,Institutionen för farmaci(Swepub:uu)hanslenn
(author)
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Uppsala universitetInstitutionen för farmaci
(creator_code:org_t)
Related titles
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In:European journal of pharmaceutics and biopharmaceutics0939-64111873-3441
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