ISSN:
1573-904X
Keywords:
phenytoin
;
prodrugs
;
prodrug hydrolysis
;
pancreatic lipase
;
lipolysis
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
Notes:
Abstract Phenytoin–lipid conjugates obtained by covalent binding of hydroxymethylphenytoin to diacylglycerides and to 3-acyloxy-2-acyl-oxymethylpropionic acids formed dispersions with a particle size of 10–200 µm when briefly sonicated in a sodium taurodeoxycholate-containing ethanol–water mixture. In contrast to the corresponding bis-deacyl derivatives, the lipids were not significantly hydrolyzed in aqueous buffers and in plasma. Incubation with pancreatic lipase yielded primarily the bis-deacyl compounds, which are comparable to monoglycerides, and subsequently liberated phenytoin. The glyceride-derived prodrugs were better substrates for the enzyme than the 3-acyloxy-2-acyloxymethyl-propionic acid derivatives. It is concluded that the phenytoin lipid conjugates are hydrolyzed by pancreatic lipase in a similar manner as natural triglycerides.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1018972419482
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