Intravenous levodopa administration in humans based on a two-compartment kinetic model.
Levodopa, when combined with a decarboxylase inhibitor, essentially delivers dopamine directly to the brain, with no net effect on brain blood vessels. For future neuroimaging studies of Parkinson disease and Tourette syndrome, we sought to rapidly produce a biologically relevant levodopa concentration in plasma and then maintain that concentration long enough to assess motor, cognitive, emotional, and neuroimaging responses, while minimizing side effects in levodopa-naive individuals. Based on available pharmacokinetic data and a two-compartment model, we designed a decreasing-exponential-rate infusion to meet these goals. This report gives results of double-blind levodopa and placebo infusions in six healthy subjects. Mean plasma levodopa concentrations were within 3% of their 1200 ng/mL target at 20 and 40 min into the infusion, and within 20% between approximately 12 and 90 min. Levodopa significantly reduced serum prolactin and raised serum growth hormone concentrations. Volunteers had no significant side effects.
Gordon
Mollie
M
Department of Psychiatry, Washington University School of Medicine, Campus Box 8134, 660 S. Euclid Avenue, St. Louis, MO 63110, USA.
Markham
Joanne
J
Hartlein
Johanna M
JM
Koller
Jonathan M
JM
Loftin
Susan
S
Black
Kevin J
KJ
D000284:Administration, Oral; D000328:Adult; D000465:Algorithms; D000978:Antiparkinson Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D001825:Body Fluid Compartments; D002230:Carbidopa / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D004298:Dopamine / Q000097:blood; D005260:Female; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D007262:Infusions, Intravenous; D007980:Levodopa / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008954:Models, Biological; D010147:Pain Measurement; D011388:Prolactin / Q000097:blood
D000978:Antiparkinson Agents; D019382:Human Growth Hormone; D007980:Levodopa; D011388:Prolactin; D002230:Carbidopa; D004298:Dopamine