Background: Chlorzoxazone (CHZ), a centrally acting skeletal muscle relaxant, is metabolized to 6- hydroxychlorzoxazone (6-OH-CHZ) by CYP2E1. CHZ can be used as an in vivo probe of CYP2E1 activity in patients with liver diseases. Pharmacokinetics of CHZ in Thai subjects should be studied for application to Thai patients.

Objective: The purpose of the present study was to determine clinical pharmacokinetics of CHZ and 6-OHCHZ.

Material and Method: Ten healthy Thai volunteers were included. After an overnight fasting, the volunteers were orally administered 400 mg CHZ and serial blood samples were collected at 0 (predose), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, and 8 hours after dosing. Plasma CHZ and 6-OH-CHZ were assayed by reversed-phase highperformance liquid chromatography (HPLC) with UV detector. The pharmacokinetic parameters including maximum concentration (C_max), time to reach maximum concentration (T_max), area under the concentrationtime curve (AUC_0-8 and AUC_0-∝), elimination half-life (t_1/2), elimination rate constant (K_el), oral clearance (Cl), and volume of distribution (Vd) were determined.

Results: CHZ was absorbed into systemic circulation with time to reach maximum concentration (T_max) of 2.00±0.82 hrs and maximum concentration (C_max) of 7.15±2.09 μg/ml. It was metabolized to 6-OH-CHZ with T_max of 3.05±1.17 hrs and C_max of 1.77±0.50 μg/ml. The extent of CHZ absorption (area under the concentrationtime curve, AUC) was 25.47±7.11 and 27.52±8.05 μg.hr/ml for AUC_0-8 and AUC_0-∝, respectively. The AUC_0-8 and AUC_0-∝ of 6-OH-CHZ were 7.32±2.21 and 8.50±2.78 μg.hr/ml, respectively. The elimination rate constant (K_el) was 0.48±0.10 and 0.40±0.13 hr^-1 for CHZ and 6-OH-CHZ, respectively. The elimination halflife (t_1/2) was 1.49±0.32 and 1.95±0.73 hours for CHZ and 6-OH-CHZ, respectively. Oral clearance (Cl) and volume of distribution (Vd) of CHZ was found to be 15.77±4.81 (L/hr) and 33.13±9.75 L, respectively.

Conclusion: An oral dose of 400 mg CHZ was used to probe for the pharmacokinetic characteristics of this drug in Thai volunteers. Those parameters reflected absorption, distribution, and elimination of CHZ in healthy Thai volunteers.

Keywords: Chlorzoxazone, Pharmacokinetics