title: Investigation of the impact of sarizotan on the pharmacokinetics of levodopa.
abstract: 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 ng h/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.
  
  
  CONCLUSIONS
  Coadministration of sarizotan with levodopa, in combination with a dopa-decarboxylase inhibitor had no effect on the pharmacokinetics or adverse event profile of levodopa.
authors.affiliation: Department of Clinical Pharmacology and Pharmacokinetics, Merck KGaA, Darmstadt, Germany. Sonja.Kroesser@merck.de
authors.forename: Sonja
authors.initials: S
authors.lastname: Krösser
authors.forename: Roland
authors.initials: R
authors.lastname: Neugebauer
authors.forename: Didier
authors.initials: D
authors.lastname: Chassard
authors.forename: Andreas
authors.initials: A
authors.lastname: Kovar
mesh_terms: D000328:Adult; D018592:Cross-Over Studies; D004347:Drug Interactions; D006801:Humans; D007980:Levodopa / Q000493:pharmacokinetics*; D008297:Male; D009930:Organic Chemicals / Q000494:pharmacology
chemical_list: D009930:Organic Chemicals; D007980:Levodopa; C443959:sarizotan