Plasma concentration of topiramate correlates with cerebrospinal fluid concentration

The authors examined the ratio between the plasma and the cerebrospinal flu id (CSF) concentration of topiramate in 14 adults with epilepsy. Simultaneo us trough samples of venous blood and CSF were collected and analyzed as to tal and unbound concentrations. Concomitant levels were also analyzed of la motrigine (n=5) and the relevant oxcarbazepine metabolite, 10-hydroxycarbaz epine (n=3). There was a close correlation between the plasma and the CSF c oncentration for both the total and unbound concentration of topiramate. Th e median CSF/plasma ratio of total topiramate was 0.85. The free topiramate concentration in plasma was not different from the free topiramate concent ration in CSF. The CSF/plasma ratios showed little variation and were indep endent of the plasma level for both the total and the unbound levels. The u nbound fraction of topiramate was 84% in plasma and 97% in CSF. The CSF con centrations of lamotrigine and 10-hydroxycarbazepine were 50% and 61% of th e plasma concentrations, respectively. For topiramate, there is a close cor relation between the plasma concentration and the CSF concentration. There does not seem to be a saturable carrier mechanism restricting topiramate tr ansport across the blood-brain barrier. The concentration of topiramate in CSF is equal to the unbound proportion of topiramate in plasma, implying th at the delivery of topiramate to the brain occurs via transfer from the unb ound plasma pool. Plasma is thus a relevant matrix for therapeutic drug mon itoring of topiramate.