Investigation of the impact of sarizotan on the pharmacokinetics of levodopa.

Objective. To investigate the effect of sarizotan on the pharmacokinetics of levodopa in fixed combination with carbidopa or benserazide. Methods. In this open-label, randomized, crossover study, healthy male subjects (n = 16) received levodopa 100 mg t.i.d. over two 5-day periods, alone or in combination with sarizotan 5 mg b.i.d. Levodopa was administered with a dopa-decarboxylase inhibitor (carbidopa 25 mg, n = 8 or benserazide 25 mg, n = 8). Pharmacokinetic parameters of levodopa were obtained on days 1 and 5. Results. ANOVA showed the C-max values for levodopa were not significantly different with or without sarizotan after single doses (1001 vs 1082 ng/ml; point estimate [PE] 1.10, 90% confidence intervals [CI] 0.83-1.45) or at steady-state (1549 vs 1663 ng/ml; PE 1.06, 90% CI 0.89-1.27); nor were AUC values for single doses (1661 vs 1665 ngh/ml; PE 1.01, 90% CI 0.91-1.11) or at steady-state (2462 vs 2482 ng h/ml; PE 1.01, 90% CI 0.97-1.05). Seven subjects reported adverse events of mild-to-moderate intensity; the most frequent were headaches and dizziness. Conclusion. Coadministration of sarizotan with levodopa, in combination with a dopa-decarboxylase inhibitor had no effect on the pharmacokinetics or adverse event profile of levodopa. Copyright (C) 2007 John Wiley & Sons, Ltd.