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Monitor drug levels for optimal therapy
Zonisamide is contraindicated in patients who have demonstrated hypersensitivity to sulfonamides or zonisamide. Consideration should be given to discontinuing zonisamide in patients who develop an otherwise unexplained rash. If the drug is discontinued, patients should be observed frequently.
Liquid chromatography/tandem mass spectrometry (LC/MS-MS)
Zonisamide is an antiepileptic drug belonging to the sulfonamide class and is chemically unrelated to other antiepileptic drugs. While the exact mechanism of action is unknown, anticonvulsant activity may be mediated by action at sodium and calcium channels. This action may result in stabilizing neuronal membranes and suppressing neuronal hypersynchronizations.1 Preliminary studies on smaller population groups has indicated possible other uses for zonisamide in intractable neuropathic pain syndromes2 and refractory migraine headaches.3
Zonisamide is excreted primarily in urine as the parent drug and glucuronide of the metabolite 2-sulfamoylacetyl phenol. Metabolism of zonisamide is mediated by the P450 isozyme CYP3A4 and to a lesser extent by CYP2D6.4 The drug was rapidly absorbed orally following 200−400 mg doses in volunteers. Peak plasma concentrations were 2−5 μg/mL and occurred in two to six hours. Food does not effect the overall bioavailability, but delays time to maximum concentration until four to six hours. Zonisamide extensively binds to erythrocytes, resulting in an eightfold higher concentration in red blood cells than in plasma. The pharmacokinetics of zonisamide are dose proportional in the range of 200−400 mg.1 Time to steady state is from 5 to 15 days with an elimination half-life of 63 to 69 hours in volunteers receiving no other medication.4 The half-life, however, is reduced by the co-medicated P450 inducers phenytoin and carbamazepine. The half-life of zonisamide is reduced to a mean of 27.1 hours when the former is co-administered and to a mean of 36.4 hours with co-administration of the latter.5
Serum or plasma
0.4 mL (Note: This volume does not allow for repeat testing.)
Red-top tube or lavender-top (EDTA) tube. Do not use a gel-barrier tube. The use of gel-barrier tubes is not recommended due to slow absorption of the drug by the gel. Depending on the specimen volume and storage time, the decrease in drug level due to absorption may be clinically significant.
Separated serum from cells within 45 minutes of collection and transfer to a plastic transport tube. Separate plasma immediately and transfer to a plastic transport tube for shipment to the laboratory. Trough: Immediately prior to next dose. Steady-state levels are reached within 5 to 15 days in patients on zonisamide monotherapy.
Causes for Rejection
Gel-barrier tube; hemolysis; nonseparated serum or plasma specimen
Refrigerate at 2°C to 8°C if specimen is not tested immediately.
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