Effect of age on the pharmacokinetics of oral levodopa in patients with Parkinson's disease

Summary The influence of age on the kinetics of a standard oral dose of levodopa administered with an inhibitor of peripheral dopa decarboxylase enzymes (benserazide) has been evaluated in 40 patients with Parkinson's disease (age 34–78 y) on chronic therapy. They were divided into 2 groups, on the basis of age below (21 patients, Group A) or above (19 patients, Group B) 65 y.The area under the plasma concentration-time curve (AUC) of levodopa was significantly greater in the older group (547 versus 428 mol·1^–1·min in Group B), coupled with a reduced apparent oral clearance (8.1 versus 10.7 ml·min^–1 ·kg^–1) and a longer plasma elimination half-life (67.6 versus 54.6 min). The age of the patients was positively correlated with the AUC of levodopa (r=0.474) and its plasma elimination half-life (r=0.391), and was negatively correlated with clearance (r=–0.489).The findings confirm previous data on volunteers that showed a reduction in the systemic clearance of levodopa due to age, which would probably account for the finding of a greater AUC of levodopa in older patients. The observed, age-mediated differences in levodopa pharmacokinetics, albeit statistically significant, were moderate and were likely to be of only minor importance for the dosing schedule.This work was part of the Progetto finalizzato Invecchiamento of the National Research Council of Italy, Grant No. 912012