Pharmacokinetics

  1. Plasma concentration

(Healthy adults, single administration of 200 mg)

Tmax (hr) Cmax (μg/mL) T1/2 (hr)
5.3± 1.3 2.9 ± 0.3 62.9 ± 1.4
Means ± standard errors

 

2. Plasma protein binding rate

48.6% (in vitro, human serum, centrifugal ultrafiltration method)

3. Main metabolites and metabolic pathway

Zonisamide is mainly metabolized in the liver and undergoes glucuronidation etc. after cleavage of isoxazole ring.

4. Excretion route & excretion rate

Excretion route: Mainly into urine.

Excretion rate: Excretion rate in urine 2 weeks after the administration was 28.9% – 47.8% as unchanged compound and 12.4 – 18.7% as main metabolites which were glucuronides of isoxazole ring cleavage compound. Those were 47.6 – 60.2% of administered dose. (Healthy adults, 200 mg administration once or twice, and 400 mg administration twice)

5. Effective blood concentration

Though it depends on severity or individual case of epilepsy, about 20 μg/mL is indicated as a standard in general.

6. Metabolic enzyme

Subtypes of cytochrome P-450: mainly CYP3A

7. Pharmacokinetics in patients with renal dysfunction

(Foreign data, single administration of 300 mg)

Creatinine clearance
(mL/min)
Tmax (h) Cmax (μg/mL) T1/2 (hr) CL (mL/min) Ae (%)
>60 3.3 3.64 58 3.42 16.8
20-60 4.3 3.73 58 2.5 11.9
<20 2.9 4.08 63 2.23 13.3
CL:renal clearance
Ae: Excretion rate into urine (Percentage of a ratio between quantity of zonisamide excreted into urine up to 8 days after the administration and its dosage.)

A difference was found between patient with renal dysfunstion and those with normal renal function in renal clearance and excretion rate into urine.