A Study on the Pharmacokinetics of Chlorzoxazone in Healthy Thai Volunteers
Nantaporn Prompila MSc*, Supeecha Wittayalertpanya MSc*, Piyawat Komolmit MD, PhD**
Affiliation : * Department of Pharmacology, Faculty of Medicine, Chulalongkorn University ** Gastroenterology Unit, Department of Medicine, Faculty of Medicine, Chulalongkorn University
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-OH-
CHZ.
Materials and Methods : 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 high-
performance liquid chromatography (HPLC) with UV detector. The pharmacokinetic parameters including
maximum concentration (Cmax), time to reach maximum concentration (Tmax), area under the concentration-
time curve (AUC0-8 and AUC0-∝
), elimination half-life (t1/2), elimination rate constant (Kel), oral clearance
(Cl), and volume of distribution (Vd) were determined.
Results : CHZ was absorbed into systemic circulation with time to reach maximum concentration (Tmax) of 2.00
+ 0.82 hrs and maximum concentration (Cmax) of 7.15 + 2.09 µg/ml. It was metabolized to 6-OH-CHZ with Tmax
of 3.05 + 1.17 hrs and Cmax of 1.77 + 0.50 µg/ml. The extent of CHZ absorption (area under the concentration-
time curve, AUC) was 25.47 + 7.11 and 27.52 + 8.05 µg.hr/ml for AUC0-8 and AUC0-∝,
respectively. The AUC0-
8 and AUC0-∝
of 6-OH-CHZ were 7.32 + 2.21 and 8.50 + 2.78 µg.hr/ml, respectively. The elimination rate
constant (Kel) was 0.48 + 0.10 and 0.40 + 0.13 hr -1 for CHZ and 6-OH-CHZ, respectively. The elimination half-
life (t1/2) 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
