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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) 9500 Euclid Avenue, L15, Cleveland, Ohio 44195 800.628.6816 | clevelandcliniclabs.com
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
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