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Does the Intake of ...
Does the Intake of Ethanol Affect Oral Absorption of Poorly Soluble Drugs?
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- Keemink, Janneke (författare)
- Uppsala universitet,Institutionen för farmaci
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- Sjögren, Erik, 1977- (författare)
- Uppsala universitet,Institutionen för farmaci,Pharmeteus, Dag Hammarskjolds Vag 52B, S-75237 Uppsala, Sweden
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- Holm, Rene (författare)
- Johnson & Johnson, Janssen R&D, Drug Prod Dev, Turnhoutseweg 30, B-2340 Beerse, Belgium
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- Bergström, Christel A. S., 1973- (författare)
- Uppsala universitet,Institutionen för farmaci
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(creator_code:org_t)
- Elsevier BV, 2019
- 2019
- Engelska.
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Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0022-3549 .- 1520-6017. ; 108:5, s. 1765-1771
- Relaterad länk:
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https://doi.org/10.1...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- The presence of ethanol in gastrointestinal (GI) fluids may increase the solubility of poorly water-soluble drugs. This suggests that intake of ethanol with such compounds could result in increased drug absorption in the stomach and duodenum because of the greater concentration gradient present. To test this hypothesis, in vitro dissolution of 2 poorly soluble compounds (indomethacin and felodipine) was studied in simulated GI rat fluids in the presence or absence of ethanol. Results were used to predict plasma exposure of the compounds using the software PK-Sim. Finally, in vivo plasma exposure in rats was investigated after oral dosing followed by immediate administration of water or ethanol. Despite increased solubility in GI fluids in the presence of ethanol, simulations predicted a negligible effect on absorption. This was confirmed in the rat study where oral intake of indomethacin or felodipine with ethanol did not increase in vivo plasma exposure. A possible explanation for the lack of an effect may be that dilution, absorption, and transfer of ethanol upon arrival in the stomach resulted in intragastric and intraduodenal ethanol concentrations that did not reach the levels required to affect local solubility.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
Nyckelord
- ethanol
- solubility
- drug absorption
- poorly water-soluble compounds
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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