A study on the pharmacokinetics of chlorzoxazone in healthy Thai volunteers
Prompila, N.; Wittayalertpanya, S.; Komolmit, P.
Journal of the Medical Association of Thailand 90(1): 160-166
2007
ISSN/ISBN: 0125-2208 PMID: 17621748 Document Number: 2685
Background: Chlorzoxazone (CHZ), a centrally acting skeletal muscle relaxant, is melabolized 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.Material and Method: Ten healthy Thai 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 time to reach maximum concentration (T-max), area under the concentration-time curve (AUC(0-8) and AUC(0-proportional to)), elimination half-life (t(12)), elimination rate constant (K-et), 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 mu g/ml. It was metaboliied to 6-OH-CHZ with T-max of 3.05 +/- 1.17 hrs and C-max of 1.77 +/- 0.50 mu g/ml. The extent of CHZ absorption (area under the concentration-time curve, AUC) was 25.47 +/- 7.11 and 27.52 +/- 8.05 mu g.hr/ml for AUC(0-8) and AUC(0-proportional to) respectively. The AUC(0-8) of 6-OH-CHZ were 7.32 +/- 2.21 and 8.50 +/- 2.78 mu g.hr/ml, respectively. The elimination rate and constant (K-cl) was 0.48 +/- 0.10 and 0.40 +/- 0.13 hr(-1) for CHZ and 6-OH-CHZ, respectively. The elimination half life (t(12)) 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.
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