Pharmacokinetics of Zonisamide after a Single Oral Administration of 100mg in Korean Healthy Subjects

건강한 한국 성인 자원자에서 Zonisamide의 약동학

Zonisamide has been used for various types of epilepsy, especially for refractory epilepsy. Method: An open-label, one-period, single-dose study was performed in 10 healthy Korean male volunteers with the approval of an institutional review board to determine the pharmacokinetics of zonisamide after a single 100 mg oral dose of zonisamide. Serial blood samples were obtained at fixed time points, over 216 h (baseline (pre-dose), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 72, 120, 168, and 216 h after administration). Zonisamide concentrations in plasma were measured by reversed-phase high-performance liquid chromatography (HPLC) with ultraviolet (UV) detector set at an wavelength of 280 nn. The results of the plasma analyses were subjected to non-compartmental pharmacokinetic analysis. Results: The maximum observed plasma zonisamide concentration $(C_{max})\;was\;1.3{\pm}0.3\;(mean{\pm}standard\;deviation){\mu}g/mL\;at\;4.0{\pm}1.6hr$ of time to reach maximum observed plasma concentration $(T_{max})$. The value of area under the plasma zonisamide concentration versus time curve from the dosing to the last quantifiable concentration $(AUC_{0-last}=87.7{\pm}15.6{\mu}g{\cdot}h/mL)$ was about 82% of AUC from the dosing to time infinity $(AUC_{0-{\infty}}=106.8{\pm}22.3{\mu}g{\cdot}h/mL)$. The calculated mean residence time (MRT) of zonisamide in the body was $128.6{\pm}23.7h$, and the means of apparent oral total body clearance (CL/F) and volume of distribution $(V_dF)4 were $0.97{\pm}0.21L/h\;and\;1.9{\pm}0.3L/kg$, respectively. Conclusion: The present pharmacokinetic data of zonisamide would be useful for designing clinical trials including the bioequivalence test in Koreans.