Estimation of topiramate in subdural cerebrospinal fluid, subcutaneous extracellular fluid, and plasma: a single case microdialysis study.
OBJECTIVE
To estimate topiramate (TPM) concentrations in subdural cerebrospinal fluid (CSF), subcutaneous extracellular fluid (ECF), and plasma and to study the correlation of TPM concentrations in these three different compartments.


METHODS
In this single case study of a patient with drug-resistant partial epilepsy undergoing presurgical evaluation with subdural EEG monitoring, we used microdialysis to estimate concentrations of unbound TPM in CSF of the subdural space and ECF of abdominal subcutaneous tissue. Blood samples were drawn for estimation of TPM concentrations in plasma.


RESULTS
The correlation between unbound TPM concentrations in subdural CSF and abdominal subcutaneous ECF was good. The mean ratio of ECF/CSF TPM concentration was 0.93 (SD+/-0.03) and the correlation coefficient was 0.98. The mean ratio of ECF/total plasma TPM was 0.75 (SD+/-0.06), and the correlation coefficient was 0.99. The mean ratio of CSF/total plasma TPM was 0.81 (SD+/-0.06), and the correlation coefficient was 0.97.


CONCLUSIONS
Assuming a protein binding of TPM of approximately 13%. it is concluded that, based on nine microdialysis samples from a single subject, TPM levels in the CSF at the cortical surface are approximately the same as the unbound plasma levels. Additional patients should be studied to confirm the results.
Lindberger
M
M
Department of Neurology, Karolinska Institute, Huddinge Hospital, Sweden.
Tomson
T
T
Ohman
I
I
Wallstedt
L
L
Ståhle
L
L
D000328:Adult; D000927:Anticonvulsants / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004828:Epilepsies, Partial / Q000134:cerebrospinal fluid* / Q000188:drug therapy* / Q000378:metabolism; D005110:Extracellular Space / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D005632:Fructose / Q000031:analogs & derivatives* / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D017551:Microdialysis; D010949:Plasma / Q000737:chemistry / Q000378:metabolism*; D012867:Skin / Q000737:chemistry / Q000378:metabolism*; D013355:Subdural Space / Q000737:chemistry / Q000378:metabolism*; D000077236:Topiramate
D000927:Anticonvulsants; D000077236:Topiramate; D005632:Fructose