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Transporter-Mediated Effects of Diclofenamic Acid and its Ascorbyl Pro-Drug in the in VivoNeurotropic Activity of Ascorbyl Nipecotic Acid Conjugate
- Source :
- Journal of Pharmaceutical Sciences; January 2004, Vol. 93 Issue: 1 p78-85, 8p
- Publication Year :
- 2004
-
Abstract
- Continuing our studies on SVCT2 ascorbic acid (AA) transporter-mediated drug delivery of neurotropic agents, we have now investigated the in vitrointracellular uptake of Diclofenac (Diclo) and its conjugate (AA-Diclo), both characterized by high affinity for the SVCT2 transporter. We have also investigated the in vivouptake mechanism of AA-conjugate of Nipecotic acid (AA-Nipec) and the implication of the transporter-mediated effects of Diclo and AA-Diclo. Diclo resulted as a noncompetitive inhibitor of AA transport, but also showed a sodium-dependent and ascorbate-independent uptake, thus implying the possible involvement of specific transporters in the delivery to the brain of Diclo. This result opens a perspective in the discovery of new strategies in the targeting of this drug to the brain. Inhibitory effects of Diclo and AA-Diclo on the SVCT2 transporter were used to study anticonvulsant effects of AA-Nipec, confirming our hypothesis of an SVCT2-mediated transport in its neurotropic activity. AA-Diclo stability has been also investigated: it is hydrolyzed following a first-order kinetics in buffer, plasma (t1/2at about 10 h) and whole blood (t1/2at about 3 h), suggesting AA-Diclo as a potential candidate to enhance the short half-life of Diclo in vivo. © 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:78–85, 2004
Details
- Language :
- English
- ISSN :
- 00223549 and 15206017
- Volume :
- 93
- Issue :
- 1
- Database :
- Supplemental Index
- Journal :
- Journal of Pharmaceutical Sciences
- Publication Type :
- Periodical
- Accession number :
- ejs37962268
- Full Text :
- https://doi.org/10.1002/jps.10532