Kinetic studies on the entry of d-amphetamine into the central nervous system: I. Cerebrospinal fluid

After intravenous administration to rats, d-amphetamine undergoes a rapid distributive phase (k approximately 0.99.min-1) during which the drug is lost from plasma. The rate of entry into the cerebrospinal fluid (CSF) is also rapid (k approximately 0.58.min-1), suggesting that the drug moves directly from plasma to CSF. Entry of drug into CSF is mainly by diffusion. Neither active transport associated with CSF formation nor active transport independent of CSF formation is quantitatively important. After intracerebroventricular injection, d-amphetamine disappears from CSF relatively slowly (k approximately 0.063.min-1). Egress of drug is mainly by diffusion (k approximately 0.044.min-1), although active transport associated with bulk absorption does play a measurable role (k approximately 0.019.min-1). At steady state, the concentration of free drug in plasma and in CSF is equivalent.