title: The Human Experience with Intravenous Levodopa.
abstract: OBJECTIVE
  To compile a comprehensive summary of published human experience with levodopa given intravenously, with a focus on information required by regulatory agencies.
  
  
  BACKGROUND
  While safe intravenous (IV) use of levodopa has been documented for over 50 years, regulatory supervision for pharmaceuticals given by a route other than that approved by the U.S. Food and Drug Administration (FDA) has become increasingly cautious. If delivering a drug by an alternate route raises the risk of adverse events, an investigational new drug (IND) application is required, including a comprehensive review of toxicity data.
  
  
  METHODS
  Over 200 articles referring to IV levodopa were examined for details of administration, pharmacokinetics, benefit, and side effects.
  
  
  RESULTS
  We identified 142 original reports describing IVLD use in humans, beginning with psychiatric research in 1959-1960 before the development of peripheral decarboxylase inhibitors. At least 2760 subjects have received IV levodopa, and reported outcomes include parkinsonian signs, sleep variables, hormone levels, hemodynamics, CSF amino acid composition, regional cerebral blood flow, cognition, perception and complex behavior. Mean pharmacokinetic variables were summarized for 49 healthy subjects and 190 with Parkinson's disease. Side effects were those expected from clinical experience with oral levodopa and dopamine agonists. No articles reported deaths or induction of psychosis.
  
  
  CONCLUSIONS
  At least 2760 patients have received IV levodopa with a safety profile comparable to that seen with oral administration.
authors.affiliation: Department of Psychiatry, Washington University School of Medicine St. Louis, MO, USA.
authors.forename: Shan H
authors.initials: SH
authors.lastname: Siddiqi
authors.affiliation: School of Epidemiology, Public Health and Preventive Medicine, University of Ottawa Ottawa, ON, Canada.
authors.forename: Natalia K
authors.initials: NK
authors.lastname: Abraham
authors.affiliation: Department of Internal Medicine, University of Washington Seattle, WA, USA.
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Geiger
authors.affiliation: Department of Neurology, Washington University School of Medicine St. Louis, MO, USA.
authors.forename: Morvarid
authors.initials: M
authors.lastname: Karimi
authors.affiliation: Programs in Occupational Therapy and Physical Therapy, Division of Biology and Biomedical Sciences, Departments of Neurology, Radiology, and Anatomy and Neurobiology, Washington University School of Medicine St. Louis, MO, USA.
authors.forename: Joel S
authors.initials: JS
authors.lastname: Perlmutter
authors.affiliation: Division of Biology and Biomedical Sciences, Departments of Psychiatry, Neurology, Radiology, and Anatomy and Neurobiology, Washington University School of Medicine St. Louis, MO, USA.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Black
keywords: DOPA; FDA; IND; Parkinson; carbidopa; intravenous; levodopa; pharmacokinetics