THERAPEUTIC ADVANTAGES OF SUSTAINED-RELEASE LEVODOPA FORMULATIONS IN PARKINSONS-DISEASE

Levodopa combined with a peripheral dopa decarboxylase inhibitor conti nues to be the primary treatment for Parkinson's disease. Since levodo pa has a short half-life, immediate release levodopa preparations lead to a rapid increase and subsequent decrease of plasma levodopa concen trations. This pharmacokinetic profile is at least partially responsib le far the reduced efficacy and fluctuating motor response that is oft en seen with long term treatment. Two sustained release levodopa formu lations (carbidopa/levodopa and benserazide/levodopa) have been develo ped to aid management of motor fluctuations. These preparations provid e smoother pharmacokinetic profiles, with levodopa concentrations sust ained substantially longer than with the immediate release formulation s. Clinical trials have demonstrated the superior efficacy of sustaine d release carbidopa/levodopa (Sinemeto(R) CR) compared with convention al, immediate release carbidopa/levodopa. Most patients with Parkinson 's disease who convert from immediate release to sustained release car bidopa/levodopa show improvement in disease symptoms. While sustained release carbidopa/levodopa does not eliminate motor fluctuations, it p rovides good maintenance of global motor response (ratio of time 'on' to 'off') for extended time periods. Conversion from immediate to sust ained release formulations is beneficial to patients with a wide range of disease severity. Conversion success is not dependent on patient d emographic variables. However, the effort and time required for conver sion relate clinically to disease severity. Sustained release benseraz ide/levodopa releases levodopa for several hours longer in vitro than the immediate release formulation. Reports of clinical trials, althoug h somewhat mixed, are generally encouraging. Neither of the 2 formulat ions of benserazide/levodopa is currently available in the US.