科研之友
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摘要
ObjectiveThe site of action for antiepileptic drugs (AEDs) is within the brain; however, cerebrospinal fluid (CSF) concentration is highly variable. Lacosamide (LCM) is approved by the U.S. Food and Drug Administration (FDA) for treatment of partial-onset seizures in adults, and has linear pharmacokinetics in serum. Penetration across the blood-brain barrier (BBB) is unknown. This study aims to provide additional insights into the pharmacokinetics of LCM. MethodsThirty adults undergoing craniotomy for treatment of intractable epilepsy or brain tumor were recruited and were either taking LCM long term (group 1, n=15), or were LCM naive, receiving LCM as prophylaxis for surgery (group 2, n=15). All patients received one intravenous (IV) dose (15min infusion) immediately prior to craniotomy. CSF and arterial blood were collected simultaneously following craniotomy. LCM concentrations were measured in serum and CSF. ResultsLCM concentration differences between groups 1 and 2 for both CSF and serum were statistically significant (p0.0005), but there was no statistically significant difference in CSF/serum ratios (group 1=0.7260.231; group 2=0.556 +/- 0.241; p=0.0585). LCM concentration in serum correlated positively with CSF concentration in group 1 (Pearson r=0.8527, p<0.0001). The time interval between the end of dose delivery and sample collection correlated positively with the CSF/serum ratio for the drug-naive group (Pearson r=0.6525; p=0.0084). Treatment with other AEDs did not affect LCM distribution between serum and CSF. SignificanceAlthough chronic dosing resulted in higher LCM concentrations in serum and CSF compared to drug-naive patients, the CSF/serum ratio was not affected by LCM pretreatment. These data suggest that LCM serum concentration may reliably predict CSF concentration.
- 出版日期2015-11
