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  • Title: Role of sphingosine synthesis inhibition in transcutaneous delivery of levodopa.
    Author: Gupta BS, Tiwary AK.
    Journal: Int J Pharm; 2002 May 15; 238(1-2):43-50. PubMed ID: 11996809.
    Abstract:
    The present study was designed to investigate the role of skin sphingosine synthesis inhibition in enhancing the in vitro permeation of levodopa (LD), a hydrophilic drug, across rat skin. beta-Chloroalanine (beta-CA), a selective inhibitor of serine palmitoyl transferase was used for inhibiting sphingosine synthesis in viable skin. The sphingosine content in viable skin perturbed by acetone treatment and immediately treated with beta-CA (600 or 1200 microg/7 cm(2)) was significantly less than that of perturbed viable skin after 36 h of treatment (P<0.001). The in vitro permeation of LD across perturbed-beta-CA treated skin was significantly greater than that across perturbed skin (P<0.001). This indicates an inverse relationship between in vitro permeation of LD and skin sphingosine content. The systemic delivery of percutaneously applied LD across normal rat skin was negligible. Higher C(max), lower T(max) and maintenance of effective plasma concentration of LD over 28 h was achieved by a single topical application of carbidopa-LD combination (1:4) to perturbed-beta-CA treated skin. Hence, skin sphingosine synthesis inhibition can be used as a novel means of enhancing systemic delivery of LD.
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