Abstract:
PURPOSE:Although levetiracetam undergoes minimum metabolism, B-esterases have been identified in whole blood that are capable of metabolising levetiracetam. The present study was designed to ascertain any variability in levetiracetam blood concentrations that could be attributed to in situ metabolism and which could impact on the utility of such concentration measurements in guiding therapeutic management. METHODS:Blood samples were collected from 40 patients that were prescribed levetiracetam. Sera (Groups 1 and 2) or whole blood (Groups 3 and 4) were compared. Paraoxan, an inhibitor of B-esterase activity, was added to samples assigned to Groups 2 and 4. Samples within each group were assigned to Time 0 (frozen within 30 min of sample collection), Time 2 days and Time 7 days (samples kept at ambient temperature for 2 and 7 days). RESULTS:For serum samples, mean levetiracetam concentrations at Time 2 days and Time 7 days were indistinguishable from Time 0, regardless of whether B-esterase activity was inhibited on not. In contrast, for whole blood, in the absence of B-esterase inhibition, mean levetiracetam concentrations declined over time (11% and 29%; 2 and 7 days) compared to baseline values. In the presence of B-esterase inhibitor, mean levetiracetam concentrations at 2 days were indistinguishable from baseline values, although at 7 days values declined by 4%. CONCLUSIONS:If therapeutic monitoring of levetiracetam is to be undertaken, serum should be the matrix of choice and that whole blood should be separated as soon as possible after patient sampling so as to minimize in situ levetiracetam metabolism which could result in spuriously low concentrations and substantial intrapatient variability.
journal_name
Epilepsiajournal_title
Epilepsiaauthors
Patsalos PN,Ghattaura S,Ratnaraj N,Sander JWdoi
10.1111/j.1528-1167.2006.00819.xsubject
Has Abstractpub_date
2006-11-01 00:00:00pages
1818-21issue
11eissn
0013-9580issn
1528-1167pii
EPI819journal_volume
47pub_type
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