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Intravenous probenecid loading

Effects on plasma and cerebrospinal fluid probenecid levels and on monoamine metabolites in cerebrospinal fluid

From the Laboratory of Neuropharmacology, National Institute of Neurological and Communicative Disorders and Stroke (Drs. Kartzinel and Chase) and the Laboratory of Clinical Science, National Institute of Mental Health, Bethesda (Dr. Ebert).

Probenecid blocks the active transport from cerebrospinal fluid to blood of homovanillic acid and 5-hydroxyindoleacetic acid, thus increasing cerebrospinal fluid levels of these products of central monoamine metabolism. The half-life in plasma of probenecid given as a single intravenous infusion (40 mg per kilogram of body weight) to patients with either Huntington's chorea or Parkinson's disease averaged about 6.6 hours. In cerebrospinal fluid, peak values for homovanillic acid and 5-hydroxyindoleacetic acid occurred in samples collected 8 hours after the 1 -hour probenecid infusion was started. Even after 4 hours, however, levels of both monoamine metabolites were significantly increased. There was a positive correlation between cerebrospinal fluid levels of probenecid and the increase in 5-hydroxyindoleacetic acid but not homovanillic acid. Compared with the oral administration of probenecid, the intravenous infusion technique produced more consistent elevations in plasma and cerebrospinal fluid probenecid levels, greater increases in cerebrospinal fluid homovanillic acid values, and fewer gastrointestinal side effects.

Dr. Chase's address is Laboratory of Neuropharmacology, National Institute of Neurological and Communicative Disorders and Stroke, 9000 Rockville Pike, Bethesda, MD 20014.

Received for publication October 13, 1975.