Pharmacokinetics of continuous-release carbidopa/levodopa

Abstract

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 characteristics of the tablet, the pattern of gastric emptying, and the rate of uptake in the small intestine; distribution, which is determined by rates of levodopa transport from gut to blood and from blood to brain; and biotransformation, which is affected peripherally by L-aromatic amino acid decarboxylase (LAAAD) and catechol-O-methyl transferase (COMT), and centrally by LAAAD, COMT, and monoamine oxidase. The kinetics of Sinemet CR are limited by rates of absorption (which depend on the dose administered), the conformation of the tablet, and daily variations in the patterns of gastric emptying (influenced by the presence or absence of food). Levodopa must also compete with food-derived amino acids for transport across the gut-blood and blood-brain barriers; this competition effectively limits the drug's rate of distribution. Finally, biotransformation is limited by the activity of LAAAD and COMT in the periphery. Plasma profiles of levodopa after administration of Sinemet CR can vary, depending on the age of the patient and the time of day when the drug is administered. Nevertheless, the pharmacokinetic profile of the preparation has a number of advantages over that of Sinemet, in that it offers a steadier climb to peak plasma concentrations that are less extreme and of greater duration.