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... more
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.
Conclusion: At least 2760 patients have received IV levodopa with a safety profile
comparable to that seen with oral administration.
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.
Conclusion: At least 2760 patients have received IV levodopa with a safety profile
comparable to that seen with oral administration.
