Abstracts

RATIONALE: Current clinical concepts of treatment with new generation AEDs forego monitoring for serum concentrations. This is based on the wide therapeutic windows suggested for these drugs. It is also implied that these AEDs have more important pharmacodynamic rather pharmacokinetic modes in deriving their effect. Clinicians are encouraged to dose drug to effect. Antiepileptic drug levels of new generation AEDs have utility in solving clinical problems of non-compliance and drug toxicity (especially in polypharmacy). Clinical experience with levetiracetam (LEV) suggested that there was clinical usefulness in monitoring antiepiletic drug levels (AEDLs) as a guide for dosing, and that serum drug levels may correlate with efficacy as measured by seizure reduction.
At the end of this session the participant should be able to discuss the potential usefulness of serum LEV concentrations and control of seizures.
METHODS: The clinical records of all patients who were introduced to LEV treatment were reviewed retrospectively. In a referral private practice, 87 patients had been treatedwith LEV at date of abstraction. Data was recorded for standard demographics, seizure types, medication use, adverse drug events, seizure frequency per month, and all LEV serum concentrations. There were 46 patients who had one or more determinations for LEV concentrations. All AEDLs were randomly drawn samples. This patient sample was reduced to include only those patients who had been followed for greater than six months of LEV treatment and who had an AEDL in the second 3 month interval. It was assumed that this interval represented a stable period of treatment following the addition of LEV and that other treatments were not being modified. Non-compliant and pseudoseizure patients were excluded. The data was analyzed by the Pearson correlation method to correlate percent seizure reduction and LEV serum concentration, dose and seizure reduction, and dose and AEDL.
RESULTS: 29 patients fulfilled our criteria. 79% patients had partial seizures and 21% had generalized seizures. Children represented less than 10% of patients. 27 patients were on multiple medications with an average of about 1.5 drugs per patient. Seizure frequencies ranged from 1 to 60 per month in the 3 month pre-treatment baseline. LEV doses ranged from 1000mg/day to 4000mg/day. Random LEV serum concentrations ranged from 6mcg/ml to 65mcg/ml. The analysis revealed a statistically significant correlation of LEV serum concentration with percent reduction of seizures (p=.0012). The r value was 0.56 which reflects variability in LEV concentrations.The results indicated the there was no correlation for dose and percent seizure reduction (p=.8066). Additionally, there was no statistical significance in correlation for dose and LEV AEDL (p=.0925).
CONCLUSIONS: There appears to a greater reduction in seizures for those patients with higher LEV concentrations. In this study we found a 75% or greater reduction in seizures if the AEDL was 35mcg/ml or higher. Dosing levetiracetam with guidance by AEDLs may be more efficient and effective than simply [dsquote]dosing to effect[dsquote]. These results warrant prospective investigations to include trough and peak AEDLs, monotherapy, inducing and non-inducing co-medications, and age controlled populations.
(Disclosure: Grant - UCB Pharma, Inc. Epilepsy Services and Research, Inc., Consulting - UCB Pharma, Inc., Materials - Epilepsy Services and Research, Inc., Royalties - Epilepsy Services and Research, Inc., Honoraria - UCB Pharma, Inc.)