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HelpTest Code ZONI Zonisamide, Serum
Reporting Name
Zonisamide, SUseful For
Monitoring zonisamide therapy; recommended for all patients to ensure appropriate dosing
Assessing medication compliance
Method Name
Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS)
Performing Laboratory
Mayo Clinic Laboratories in Rochester
Specimen Type
Serum RedSpecimen Required
Supplies: Sarstedt Aliquot Tube, 5 mL (T914)
Collection Container/Tube: Red top (serum gel/SST is not acceptable)
Submission Container/Tube: Plastic vial
Specimen Volume: 1 mL
Collection Instructions: Centrifuge and aliquot serum into plastic vial within 2 hours of collection.
Specimen Minimum Volume
0.5 mL
Specimen Stability Information
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Serum Red | Refrigerated (preferred) | 28 days | |
| Ambient | 28 days | ||
| Frozen | 28 days |
Reject Due To
| Gross hemolysis | OK |
| Gross lipemia | OK |
| Gross icterus | OK |
Reference Values
10-40 mcg/mL
Day(s) Performed
Monday through Saturday
CPT Code Information
80203
LOINC Code Information
| Test ID | Test Order Name | Order LOINC Value |
|---|---|---|
| ZONI | Zonisamide, S | 29620-2 |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| 83685 | Zonisamide, S | 29620-2 |
Clinical Information
Zonisamide (Zonegran) is approved as adjunctive therapy for partial seizures refractory to therapy with traditional anticonvulsants. Zonisamide is the pharmacologically active agent; its metabolites are not active. Essentially 100% of the zonisamide dose is absorbed. Approximately 88% of circulating zonisamide is bound to erythrocytes. The relationship between the serum level and dose is not linear because erythrocyte-bound zonisamide is inactive and binding varies with blood concentration. Time to peak zonisamide concentration is 2 to 6 hours; time to peak is delayed by coadministration with food to 4 to 6 hours. Zonisamide is metabolized by N-acetyl transferase (NAT1), cytochrome P450 3A4 (CYP3A4), and uridine diphosphate glucuronidation (UDPG). Zonisamide is eliminated in the urine predominantly as the parent drug (35%), N-acetyl zonisamide (15%), and as the glucuronide ester of reduced zonisamide (50%). Coadministration of drugs that affect NAT1, CYP3A4, and UDPG activity, such as phenytoin and carbamazepine, will decrease zonisamide concentration.
A typical zonisamide dose administered to an adult is 400 to 600 mg/day, administered in 2 divided doses. The apparent volume of distribution of zonisamide is 1.5 L/kg. Approximately 40% of the zonisamide circulating in the serum is bound to proteins. Zonisamide protein binding is unaffected by other common anticonvulsant drugs. The elimination half-life from plasma is 50 to 60 hours; the elimination half-life from erythrocytes is over 100 hours. Since zonisamide is cleared predominantly by the kidney, the daily dosage of zonisamide given to patients with a creatinine clearance below 20 mL/min should be reduced.(1,2)
Serum level monitoring is recommended for all patients to ensure appropriate dosing because:
-Patient response correlates with serum level.
-Serum level does not correlate with dose because of concentration-dependent erythrocyte binding.
-Elimination is affected by coadministration of drugs that affect NAT1, CYP3A4, and UDPG.
-Kidney function affects elimination.
The most common toxicity associated with excessive serum level is drowsiness. Adverse effects not related to serum level include rash, increased serum creatinine and alkaline phosphatase, kidney stone formation, and bruising.
Interpretation
Steady-state zonisamide concentration in a trough specimen collected just before next dose correlates with patient response but not with dose. Optimal response to zonisamide occurs when trough zonisamide concentration is in the range of 10 to 40 mcg/mL. Peak serum concentration for zonisamide occurs 2 to 6 hours after dose, and time to peak is affected by food intake.
Because carbamazepine activates glucuronidation, patients taking carbamazepine concomitantly with zonisamide have significantly lower zonisamide concentrations compared to patients on the same dose not receiving carbamazepine.
Cautions
Rufinamide is a known interference of this assay. Patients who are coadministered zonisamide and rufinamide may have falsely elevated and uninterpretable zonisamide concentrations reported by this assay.
Method Description
The serum sample is deproteinated with acetonitrile containing the deuterium labeled internal standard. The protein precipitate is centrifuged, and a portion of the supernatant is diluted with mobile phase for detection by tandem mass spectrometry.(Unpublished Mayo method)