PHARMACOKINETICS OF CONTINUOUS-RELEASE CARBIDOPA LEVODOPA/

This article reviews the pharmacokinetics of Sinemet CR, a controlled- release (CR) levodopa preparation. The main influences on the kinetic profile are as follows: absorption, which depends on the dissolution c haracteristics of the tablet, the pattern of gastric emptying, and the rate of uptake in the small intestine; distribution, which is determi ned by rates of levodopa transport from gut to blood and from blood to brain; and biotransformation, which is affected peripherally by L-aro matic amino acid decarboxylase (LAAAD) and catechol-O-methyl transfera se (COMT), and centrally by LAAAD, COMT, and monoamine oxidase. The ki netics of Sinemet CR are limited by rates of absorption (which depend on the dose administered), the conformation of the tablet, and daily v ariations in the patterns of gastric emptying (influenced by the prese nce or absence of food). Levodopa must also compete with food-derived amino acids for transport across the gut-blood and blood-brain barrier s; this competition effectively limits the drug's rate of distribution . Finally, biotransformation is limited by the activity of LAAAD and C OMT in the periphery. Plasma profiles of levodopa after administration of Sinemet CR can vary, depending on the age of the patient and the t ime of day when the drug is administered. Nevertheless, the pharmacoki netic profile of the preparation has a number of advantages over that of Sinemet, in that it offers a steadier climb to peak plasma concentr ations that are less extreme and of greater duration.