Improved delivery through biological membranes. 4. Prodrugs of L-dopa.
Various classes of transient derivatives of L-Dopa have been synthesized, systematically protecting one or more of the main sites of metabolism in the molecule: the carboxy function, the amino, and/or the catechol system. The derivatives studied include carboxy esters, phenol esters, amides, peptides, and various combinations of these functions. A number of these derivatives effectively prevent the metabolism of L-Dopa prior to and/or during the absorption process, resulting in a significantly better bioavailability of the drug. In vivo studies using dogs showed up to 2.5-fold increase in L-Dopa blood levels. The metabolism as well as toxicity aspects of the prodrugs is also discussed.
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D004285:Dogs; D007408:Intestinal Absorption; D007928:Lethal Dose 50; D007980:Levodopa / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism; D008297:Male; D051379:Mice; D013608:Tablets, Enteric-Coated
D013608:Tablets, Enteric-Coated; D007980:Levodopa