In situ metabolism of levetiracetam in blood of patients with epilepsy.
OBJECTIVE
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.
Patsalos
Philip N
PN
Pharmacology and Therapeutics Unit, Department of Clinical and Experimental Epilepsy, Institute of Neurology, London, United Kingdom. p.patsalos@ion.ucl.ac.uk
Ghattaura
Sandirup
S
Ratnaraj
Neville
N
Sander
Josemir W
JW
D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000097:blood / Q000378:metabolism* / Q000627:therapeutic use*; D001800:Blood Specimen Collection; D002851:Chromatography, High Pressure Liquid; D016903:Drug Monitoring; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004827:Epilepsy / Q000097:blood* / Q000188:drug therapy* / Q000378:metabolism; D004950:Esterases / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism; D005260:Female; D006801:Humans; D000077287:Levetiracetam; D008297:Male; D008875:Middle Aged; D010889:Piracetam / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism / Q000627:therapeutic use; D013997:Time Factors
D000927:Anticonvulsants; D004791:Enzyme Inhibitors; D000077287:Levetiracetam; D004950:Esterases; D010889:Piracetam