Update on Levodopa/Carbidopa Intestinal Gel Infusion

In 1975, it was shown that achieving stable plasma levodopa levels by continuous intravenous infusion of levodopa rapidly stabilised motor fluctuations in Parkinson’s disease (PD) patients.¹ However, intravenous levodopa infusion did not become a practical treatment option in PD because of the technical complexity of administration.² In the mid-1980s, it was shown that enteral (duodenal/jejunal) infusion of levodopa achieved stable plasma levodopa concentrations and reduced motor fluctuations,³ but the large volumes of levodopa/carbidopa solutions involved were cumbersome and impractical. It was only when a gel formulation of levodopa/carbidopa was developed that enteral infusion became a viable therapy. This levodopa/carbidopa intestinal gel (LCIG) infusion therapy has undergone further development and testing in patients.^4,5 The recent data on this therapy, collected until May 2011, are discussed in this article.

Recent Findings on Levodopa/Carbidopa Intestinal Gel Infusion Pharmacokinetics and Pharmacodynamics
Several recent studies have examined the pharmacokinetics and pharmacodynamics of LCIG infusion treatment. One of these studies aimed to identify and estimate characteristic parameters of a population pharmacokinetic-pharmacodynamic model for LCIG infusion, in order to better understand the pharmacological properties of this levodopa formulation.⁶ A model was developed based on pooled data from three studies in patients with advanced Parkinson’s disease (APD).

The study showed that absorption of LCIG can be adequately described with first-order absorption (mean absorption time of 28.5 minutes) with a bioavailability of 88 % and a lag time of 2.9 minutes. The parameters were relatively well determined, with standard errors of 4–43 %. The best pharmacodynamic model was of the effect compartment sigmoid E_max type with a steep sigmoidicity coefficient (Hill=11.6), a half-life of effect delay of 21 minutes, a concentration at 50 % effect of 1.55 mg/l, and an E_max of 2.39 units on the treatment response scale. This model may be a first step towards model-guided treatment individualisation of LCIG infusion.

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