Abstracts

RATIONALE: The use of Thearpeutic Drug Monitoring rests on the principle that the concentration in bodily fluids (eg. plasma) reflects the concentration and effect of a drug in the effector organ (in this case the brain). We examined the relationship between plasma and cerebrospinal concentrations of Topiramate in adult, epilepsy patients in order to elucidate the potential value of plasma samples in Therapeutic Drug Monitoring. METHODS: Cerebrospinal fluid was obtained from patients by lumbar puncture prior to the morning dose at steady state Topiramate therapy. At the same time a blood sample was obtained for analysis of Topiramate in plasma. Drug Analysis was performed using fluorescence polarization immunoassay technology (Innofluor?, Oxis Internatioal, Inc.) on a TDx? analyzer (Abbott Laboratories, Inc.) Samples were analysed for the total concentration of Topiramate. Data were analyzed using SPSS version 8.0. RESULTS: Fourteen patients (5 men and 9 women) completed the study. Ratio was 0,83 between cerebrospinal fluid and plasma concentrations - eqivivalent to the unbound fraction of Topiramate in plasma. The ratio had a low coefficient of variation = 14% and did not increase or decrease with the Topiramate level. There was a close correlation between the plasma concentration and the cerebrospinal fluid concentration (correlation coefficient = 0,99, p<0,01). CONCLUSIONS: We conclude that there does not seem to be a saturable carrier mechanism restricting Topiramate transport across the blood brain barrier. The close correlation between plasma and cerebrospinal fluid concentration implies that the delivery of Topiramate to the brain occur via transfer from the unbound plasma pool to the cerebrospinal fluid. Plasma is thus a relevant matrix for Therapeutic Drug Monitoring of Topiramate.