Significant amounts of zonisamide are cleared by both the renal and hepatic routes.77 The clearance of zonisamide has been shown to decrease with decreasing creatinine clearance.78 In patients with severe renal impairment (creatinine clearance less than 20 mL/min), the mean plasma concentration of zonisamide increased by 35%.78 No specific guidelines for dosage reductions in renal insufficiency have been provided. Frequent monitoring of such patients is recommended.
Zonisamide is moderately soluble in water, is 40% protein bound, and has a moderate volume of distribution. There are no clinical studies of the effects of hemodialysis on zonisamide plasma concentration.49 The pharmacokinetics of zonisamide suggests there will be some loss of drug with hemodialysis.
Reviewed and revised February 2004 by Steven C. Schachter, MD, epilepsy.com Editorial Board.
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