Effects of food on the pharmacokinetics of levodopa in a dual-release formulation.

The objective was to assess the effect of food on the pharmacokinetics of levodopa and 3-O-methyldopa after administration of a new levodopa/benserazide formulation with a dual-release drug delivery profile (Madopar DR). In an open-label, two-way cross-over study, 19 healthy volunteers who had fasted overnight were randomized to receive a single oral dose of levodopa/benserazide (200/50 mg) in the absence or presence of a standardized, high-fat breakfast, administered 30 min before drug administration. The treatment periods (fasting, non-fasting) were preceded by a baseline regimen of levodopa/benserazide (100/25 mg t.i.d. for 6 or 7 days). Blood samples were taken at specific times over a 12-hour period. Plasma concentrations of levodopa and 3-O-methyldopa were determined by high-performance liquid chromatography for pharmacokinetic evaluation. The parameter C(max) of levodopa was significantly lower and t(max) longer under postprandial conditions than under fasting conditions (mean C(max) 1.41 vs. 2.09 mg l(-1); mean t(max) 3.1 vs. 1.0 h). With food, the area under the curve (AUC) of levodopa was equivalent to that following an overnight fast. Compared with volunteers who had fasted, food did not alter t(1/2). Estimates of C(max), t(max) and AUC of 3-O-methyldopa under non-fasting conditions were not significantly different from those under fasting conditions. In conclusion, food decreases the rate of levodopa absorption, but had no effect on the systemic exposure to levodopa and the degree of 3-O-methyldopa formation. Standardization of levodopa/benserazide administration with respect to meal times is recommended.