| Enhanced cellular uptake of Ara-C via a peptidomimetic prodrug, L-valyl-ara-C in Caco-2 cells. | |
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MedLine Citation:
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PMID: 16805952 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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This study aimed to investigate the gastrointestinal stability and the cellular uptake characteristics of L-valyl-ara-C, a peptidomimetic prodrug of ara-C (cytarabine). After the synthesis of L-valyl-ara-C via the incorporation of L-valine into the N4-amino group of the cytosine ring in araC, the gastrointestinal stability of L-valyl-ara-C was examined using artificial gastric juice and artificial intestinal fluids. The cellular uptake characteristics of L-valyl-ara-C were also examined in Caco-2 cells. The disappearance half-life of L-valyl-ara-C was 2.2 h in artificial gastric juice, while the degradation of L-valyl-ara-C was negligible in artificial intestinal fluid and also in the supernatant above the Caco-2 cell monolayer during the 2-h incubation. The cellular accumulation of L-valyl-ara-C was 5-fold higher than that of ara-C in Caco-2 cells. Furthermore, the cellular uptake of L-valyl-ara-C did not increase proportionally to the increase in drug concentration. The cellular accumulation of L-valyl-ara-C was significantly reduced in the presence of uridine, p-aminohippurate, tetraethylammonium and small dipeptides, while it was not changed in the presence of L-valine and benzoic acid, suggesting that L-valyl-ara-C could interact with multiple uptake transporters, including peptide transporters, organic anion and cation transporters and nucleoside transporters, but might not interact with amino acid transporters. In conclusion, L-valyl-ara-C could be effective to improve the oral absorption of ara-C via the carrier-mediated transport pathway. |
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Authors:
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Eun-Pa Cheon; Joon Hee Hong; Hyo-Kyung Han |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The Journal of pharmacy and pharmacology Volume: 58 ISSN: 0022-3573 ISO Abbreviation: J. Pharm. Pharmacol. Publication Date: 2006 Jul |
Date Detail:
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Created Date: 2006-06-29 Completed Date: 2006-12-11 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0376363 Medline TA: J Pharm Pharmacol Country: England |
Other Details:
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Languages: eng Pagination: 927-32 Citation Subset: IM |
Affiliation:
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College of Pharmacy, Chosun University, 375 Seosuk-dong, Gwangju, Korea. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Biological Transport Caco-2 Cells Chromatography, High Pressure Liquid Cytarabine / analogs & derivatives*, chemical synthesis, chemistry, pharmacokinetics Drug Stability Gastric Juice / chemistry Half-Life Humans Intestinal Secretions / chemistry Intestines / metabolism Peptides / chemistry* Prodrugs / chemical synthesis, chemistry, pharmacokinetics* |
| Chemical | |
Reg. No./Substance:
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0/L-valyl-ara-C; 0/Peptides; 0/Prodrugs; 147-94-4/Cytarabine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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