Technical Brief
Measurement of Levetiracetam in Serum or Plasma
Background Information Interpretation
Levetiracetam (Keppra, UCB Inc, Smyrna, Ga.) is an
Results are reported in units of μg/mL (micrograms/mL).
anti-convulsant drug available in the United States
The Lab Test and Diagnostic Procedure Handbook
since 2000. The drug’s initial FDA-approved indication (Lexi-Comp) reports a therapeutic range of 5-45 μg/mL was for adjunctive therapy of partial-onset seizures in
(approx 29-265 μmol/L) when levels are obtained to
adults, but additional indications have been subse-
evaluate for poor clinical response, signs of toxicity,
quently approved. It has excellent oral bioavailability
onset of seizures, changes in concurrent medication,
(>95%) and is renally excreted, with 66% of the drug or suspected noncompliance. present in urine unchanged, and 24% present as the
Limitations of the Assay
primary metabolite, which is pharmacological y inactive. Hepatic metabolism of the drug has not been demon-
Serum or plasma specimens may be stored up to one
strated, so changes in cytochrome P450 expression
week refrigerated; if testing is delayed beyond one week,
levels and activities, as well as interactions with other
specimens may be stored frozen up to four weeks. To
drugs, are unlikely. Plasma half-life of levetiracetam in optimize individual patient care, specimens from the otherwise healthy individuals is 6-8 hours.
same matrix should be used for tracking and/or result comparisons. Interference by other anti-epileptic drugs
High performance liquid chromatography (HPLC)
and the primary metabolite of levetiracetam (ucbL057)
of extracted samples has been available as a moni-
was evaluated by the immunoassay manufacturer and
toring methodology for several years. In 2009, a
510(k) FDA-cleared, homogeneous immunoassay for levetiracetam monitoring in serum and plasma was
Methodology
introduced, with advantages that include reduced
The levetiracetam immunoassay (ARK Diagnostics,
turnaround time and sample preparation, leading to
Sunnyvale, Calif.) was adapted for use on the ADVIA
potential improvements in patient care.
1200 automated chemistry analyzer (Siemens Health-
Clinical Indications
care Diagnostics, Deerfield, Ill.). This platform allows for random access analysis and small sample volumes.
Although levetiracetam is recognized for its ease of
The immunoassay is homogeneous and utilizes an
dosing and tolerability, monitoring serum/plasma con-
antibody against levetiracetam. The reagents include
centrations may be indicated in patients with conditions levetiracetam labeled with the enzyme glucose-6-
that often alter pharmacokinetic characteristics, such as phosphate dehydrogenase (G6PDH), which competes
renal impairment, pregnancy, or older age. Monitoring
with analyte from the patient specimen for binding to
also may be useful to optimize regimens in individual
the antibody. Antibody binding to the labeled drug-en-
patients, to guide dosing in newer extended-release
zyme complex reduces the enzyme activity. Increased
formulations, or to investigate therapeutic failure or
concentration of drug from the patient specimen,
therefore, results in increased activity of (unbound)
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drug-enzyme complex. The reaction converts NAD to
Related Tests
NADH, which is monitored spectrophotometrically.
Assays for monitoring many other anti-epileptic drugs
A method comparison between the new immunoassay are available and may be ordered in conjunction with and HPLC-UV as a reference method was carried out
levetiracetam concentration. Additional tests require
using leftover specimens from patients on levetiracetam larger sample volumes. therapy. As illustrated in figure 1, the immunoassay
Suggested Reading
correlated very well with the HPLC-UV data
1. http://www.ark-tdm.com/pdfs/MKT09-003_Rev02_v04
ARKLevetiracetamDS_091216.pdf. 2. Crepeau AZ, Treiman DM. Levetiracetam: a comprehensive
review. Expert Rev Neurother. 2010 Feb;10(2):155-7.
3. Johannessen SI, Tomson T. Pharmacokinetic variability of
newer antiepileptic drugs: when is monitoring needed?
Clin Pharmacokinet. 2006;45(11):1061-75.
4. Johannessen SI, Battino D, Berry DJ, Bialer M, Kramer
G, Tomson T et al. Therapeutic drug monitoring of the
newer antiepileptic drugs. Ther Drug Monit. 2003 Jun;25(3):347-63.
5. Matar KM. Quantification of levetiracetam in human
plasma by liquid chromatography-tandem mass spec-trometry: application to therapeutic drug monitoring. J Pharm Biomed Anal. 2008 Nov 4;48(3):822-8.
6. Curtis EG, Patel JA. Enzyme multiplied immunoassay
technique: a review. CRC Crit Rev Clin Lab Sci. 1978;9(4):303-20. HPLC (ug/mL) Test Overview Test Name Reference Range Patient Preparation
For trough level, draw prior to next dose; for peak level, draw 1.0-1.5 hours after oral dosing
Specimen Requirements
Serum or plasma (EDTA or heparin) without gel separator; Minimum volume: 0.05 mL
Ordering Mnemonic Billing Code Technical Information Contact: Scientific Information Contact:
PD Dr.med. A. Trotter, Seite 1 von 4, 21.03.2013 Schriftenverzeichnis 2012, Trotter A, Steinmacher J, Kron M, Pohlandt F. Neurodevelopmental Follow-up at 5 Years Corrected age of Extremely Low Birth Weight Infants after Postnatal Replacement of Estradiol and Progesterone. J Clin Endocrinol Metab: 95; 1041-1047 2010 , Trotter A, Pohlandt F. Aktuelle Ergebnisqualität der Versorgung
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