L‐Dopa pharmacokinetics in plasma and cisternal and lumbar cerebrospinal fluid of monkeys

The pharmacokinetics of levodopa (L‐dopa) in plasma and in cisternal and lumbar cerebrospinal fluid (CSF) were studied in Rhesus monkeys that were given 2‐ to 3‐hour intravenous infusions of L‐dopa. Steady‐state L‐dopa concentrations in cisternal CSF correlated well with plasma levels, and yielded a CSF: plasma ratio of 0.17. The disappearance of L‐dopa from plasma and cisternal CSF compartments fits an open, two‐compartment pharmacokinetic model. Although slower, the distribution and elimination half‐lives for L‐dopa from cisternal CSF (8.9 and 49.2 minutes, respectively) were of a similar magnitude to those from plasma (4.9 and 33.2 minutes, respectively). If cisternal CSF reflects brain extracellular fluid, then plasma pharmacokinetics of L‐dopa are a reasonable approximation of those in the brain. In contrast to cisternal CSF, the disappearance of L‐dopa from lumbar CSF fits an open, one‐compartment model with an elimination half‐life of 100 minutes. This indicates that the lumbar CSF compartment is unsuitable for investigation of the pharmacokinetics of L‐dopa in the brain.