THE EFFECT OF TOLCAPONE ON LEVODOPA PHARMACOKINETICS IS INDEPENDENT OF LEVODOPA CARBIDOPA FORMULATION/

Clinical pharmacology studies have shown that the catechol-O-methyltra nsferase inhibitor tolcapone increases the bioavailability area under the plasma concentration-time curve (AUC) and the plasma elimination h alf-life (t(1/2)) of levodopa. The objective of the study was to evalu ate the pharmacokinetics of levodopa and 3-O-methyldopa (3-OMD) after coadministration of tolcapone 200 mg with levodopa/carbidopa carbidopa in the following doses: 100/10 mg, 100/25 mg, 200/20 mg, 200/50 mg, 2 50/25 mg (all immediate-release) and 200/50 mg (controlled-release). T hirty healthy male volunteers were divided into four groups: three gro ups of 8 and one group of 6. Participants in the first three groups re ceived two formulations of levodopa/carbidopa. Each dose was administe red on two occasions, once with tolcapone 200 mg and once with placebo (four-way crossover). in the fourth group. one formulation nias given on two occasions, once with tolcapone 200 mg and once with placebo (t wo-way crossover). Dosing days were separated by a 7-day washout. The effect of tolcapone on levodopa and 3-OMD pharmacokinetics was found t o be similar with all levodopa/carbidopa formulations. The absorption of levodopa was unaffected by tolcapone in all treatment groups and th e maximum plasma concentration (C-max) remained unchanged. When tolcap one was given with the immediate-release formulations, levodopa AUC in creased by 60-90% and levodopa t(1/2) by 20-60%. With tolcapone and th e controlled-release formulation, AUC increased by 80% and t(1/2) by 6 0%. With all levodopa/carbidopa formulations, 3-OMD C-max decreased by 80% and AUC by 70% with tolcapone. The tolerability of all treatment combinations was similar. We conclude that adjunctive treatment with t olcapone should have similar levodopa-potentiating clinical effects, r egardless of the levodopa/carbidopa formulation.