Effect of alteration of cerebrospinal fluid bulk flow on nicotine cerebrospinal fluid exit transfer kinetics

This study was undertaken to determine if a compound which alters the bulk flow of cerebrospinal fluid (CSF) alters the elimination kinetics of a compound in the CSF. Acetazolamide was chosen as the CSF bulk flow-altering agent. It produces a relatively large effect on the flow process, affecting both choroidal and extrachoroidal CSF production, and has been shown to affect CSF flow following iv administration. The compound monitored was nicotine. Acetazolamide was administered orally for one week before and intravenously during the experiment. Nicotine was administered by a bolus injection directly into the CSF via the cisterna magna. The results indicate that the introduction of acetazolamide into the general circulation increases the rate of removal of nicotine from the CSF. Subjects receiving acetazolamide had elevated CSF pressures. The increase in CSF pressure associated with the administration of acetazolamide suggests pressure as a possible factor in the observed increase in the rate of removal of nicotine.