Transport of amino acid esters and the amino-acid-based prodrug valganciclovir by the amino acid transporter ATB(0,+).

Article Details

Citation

Copy to clipboard

Umapathy NS, Ganapathy V, Ganapathy ME

Transport of amino acid esters and the amino-acid-based prodrug valganciclovir by the amino acid transporter ATB(0,+).

Pharm Res. 2004 Jul;21(7):1303-10.

PubMed ID

15290873 [ View in PubMed

]

Abstract

PURPOSE: The purpose of this study was to analyze the transport of amino acid esters and the amino-acid-based prodrug valganciclovir by the Na(+)/Cl(-)-coupled amino acid transporter ATB(0,+). METHODS: The interaction of amino acid esters and valganciclovir with the cloned rat ATB(0,+) was evaluated in a mammalian cell expression system and in the Xenopus oocyte expression system. RESULTS: In mammalian cells, expression of ATB(0,+) induced glycine uptake. This uptake was inhibited by valine and its methyl, butyl, and benzyl esters. The benzyl esters of other neutral amino acids were also effective inhibitors. Valganciclovir, the valyl ester of ganciclovir, was also found to inhibit ATB(0,+)-mediated glycine uptake competitively. Exposure of ATB(0,+)-expressing oocytes to glycine induced inward currents. Exposure to different valyl esters (methyl, butyl, and benzyl), benzyl esters of various neutral amino acids, and valganciclovir also induced inward currents in these oocytes. The current induced by valganciclovir was saturable with a K0.5 value of 3.1+/-0.7 mM and was obligatorily dependent on Na+ and Cl-. The Na+:Cl-:valganciclovir stoichiometry was 2 or 3:1:1. CONCLUSIONS: Amino acid esters and the amino-acid-based prodrug valganciclovir are transported by ATB(0,+). This shows that ATB(0,+) can serve as an effective delivery system for amino acid-based prodrugs.

DrugBank Data that Cites this Article

Drugs

Valganciclovir

Drug Transporters

Drug	Transporter	Kind	Organism	Pharmacological Action	Actions
Valaciclovir	Sodium- and chloride-dependent neutral and basic amino acid transporter B(0+)	Protein	Humans	Unknown	Not Available	Details
Valganciclovir	Sodium- and chloride-dependent neutral and basic amino acid transporter B(0+)	Protein	Humans	Unknown	Not Available	Details