دورية
Transport of L-valine-acyclovir via the oligopeptide transporter in the human intestinal cell line, Caco-2.
| العنوان: | Transport of L-valine-acyclovir via the oligopeptide transporter in the human intestinal cell line, Caco-2. |
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| المؤلفون: | L, de Vrueh R, L, Smith P, P, Lee C |
| المصدر: | The Journal of Pharmacology and Experimental Therapeutics; September 1998, Vol. 286 Issue: 3 p1166-70, 5p |
| مستخلص: | It has been reported that conjugating acyclovir, a potent antiviral with low oral bioavailability, to L-valine increases its urinary excretion in rats. However, it was also reported that this increase is not found for the D-valine ester, suggesting that a carrier-mediated mechanism is involved in its intestinal absorption. Therefore, mechanisms involved in the transepithelial transport of L-valine-acyclovir were investigated using the intestinal cell line, Caco-2, as a model system for the intestinal epithelium. Only the mucosal-to-serosal transport of acyclovir was increased by conjugation with L-valine (approximately 7-fold), suggesting the involvement of a carrier-mediated mechanism. This conclusion was supported by the finding that this increase was saturable. The mucosal-to-serosal transport of L-valine-acyclovir could be inhibited by L-glycylsarcosine, but not by L-valine, suggesting the involvement of the dipeptide carrier. Also it was found that L-valine-acyclovir inhibits the uptake of cephalexin, a substrate for the oligopeptide transporter. Stability of the esters in either the mucosal or serosal bathing solution is more than 90% after completion of the transport study. However, after transport, the receiver solution contained approximately 90% of acyclovir. Based on these findings it was concluded that absorption of the L-valine ester of acyclovir occurs as a result of uptake by the oligopeptide transporter at the apical cell membrane followed by intracellular hydrolysis of the ester and efflux of acyclovir. |
| قاعدة البيانات: | Supplemental Index |
| تدمد: | 00223565 15210103 |
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