| Multiple transport mechanisms involved in the intestinal absorption and first-pass extraction of fexofenadine. | |
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MedLine Citation:
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PMID: 14586383 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: Our objective was to investigate the main in vivo transport mechanisms of fexofenadine involved in the intestinal absorption and bioavailability of the drug in humans. METHODS: A jejunal single-pass perfusion study was performed in 10 healthy volunteers. Each experiment lasted for 200 minutes and was divided into 2 periods of 100 minutes. During the control period (0-100 minutes), the jejunal segment was perfused with 100 mg/L (186-micromol/L) fexofenadine. In the treatment period (100-200 minutes), fexofenadine was coperfused with 500 mg/L (1018-micromol/L) of the membrane transport inhibitor verapamil. The concentrations of fexofenadine in the perfusate and plasma were measured by HPLC with ultraviolet and mass detection, respectively. RESULTS: Verapamil did not significantly affect the human effective jejunal permeability of fexofenadine. The mean (+/-SD) effective jejunal permeability values were 0.06 +/- 0.07. 10(-4) cm/s and 0.04 +/- 0.07. 10(-4) cm/s in the control and treatment periods, respectively. However, verapamil increased the apparent absorption rate constant into the systemic circulation and the area under the plasma concentration-time curve for fexofenadine from 0.0030 +/- 0.0012 min(-1) to 0.0255 +/- 0.0103 min(-1) (P <.001) and from 161 +/- 181 ng/mL x min to 664 +/- 537 ng/mL x min (P <.01), respectively. CONCLUSIONS: In this in vivo perfusion study verapamil increased the bioavailability of fexofenadine. Because the permeability, which is a direct measure of intestinal transport, was unchanged, we suggest that the major reason for this effect was decreased first-pass liver extraction of fexofenadine. The most plausible mechanism is either decreased organic anion transporting polypeptide-mediated sinusoidal uptake or P-glycoprotein-mediated canalicular secretion of fexofenadine, or both. |
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Authors:
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Christer Tannergren; Niclas Petri; Lars Knutson; Mikael Hedeland; Ulf Bondesson; Hans Lennernäs |
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Publication Detail:
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Type: Clinical Trial; In Vitro; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Clinical pharmacology and therapeutics Volume: 74 ISSN: 0009-9236 ISO Abbreviation: Clin. Pharmacol. Ther. Publication Date: 2003 Nov |
Date Detail:
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Created Date: 2003-10-30 Completed Date: 2003-11-21 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0372741 Medline TA: Clin Pharmacol Ther Country: United States |
Other Details:
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Languages: eng Pagination: 423-36 Citation Subset: AIM; IM |
Affiliation:
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Department of Pharmacy, Uppsala University, Uppsala, Sweden. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adult Algorithms Anti-Allergic Agents / pharmacokinetics* Area Under Curve Biological Availability Calcium Channel Blockers / pharmacology Chromatography, High Pressure Liquid Female Humans Intestinal Absorption* / drug effects Intestines / blood supply Jejunum / blood supply, metabolism Male Membrane Transport Modulators Membrane Transport Proteins / antagonists & inhibitors, metabolism* Regional Blood Flow / physiology Spectrophotometry, Ultraviolet Terfenadine / analogs & derivatives*, pharmacokinetics* Verapamil / pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Anti-Allergic Agents; 0/Calcium Channel Blockers; 0/Membrane Transport Modulators; 0/Membrane Transport Proteins; 138452-21-8/fexofenadine; 50679-08-8/Terfenadine; 52-53-9/Verapamil |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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