Absorption, Distribution and Excretion
Chlorzoxazone is rapidly metabolized and is excreted in the urine, primarily in a conjugated form as the glucuronide.

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Metabolism / Metabolites
Chlorzoxazone is rapidly metabolized in the liver and is excreted in the urine, primarily in a conjugated form as the glucuronide.
Chlorzoxazone has known human metabolites that include 6-Hydroxychlorzoxazone.

Hepatotoxicity
There have been no adequate prospective studies demonstrating the rates of ALT or AST elevations on chlorzoxazone therapy. Rare instances of clinical apparent liver disease possibly attributable to chlorzoxazone have appeared, including fatal cases. Such cases must be very rare, as this agent is widely used. While case reports have been few, in many instances chlorzoxazone was clearly implicated; furthermore, a related muscle relaxant with similar structure (zoxazolamine) was withdrawn from use in 1961, largely because of hepatotoxicity. The usual latency period is 1 to 4 weeks and the pattern of disease typically hepatocellular with marked elevations in ALT levels and jaundice, with minimal increases in alkaline phosphatase. Cholestatic enzyme elevations after exposure to chlorzoxazone have also been described. Allergic manifestations (rash and fever) are common, particularly in cases with a short latency (Case 1); autoantibodies are rare. Recovery is rapid once chlorzoxazone is stopped, but fatal cases have been reported, with disease progression despite early discontinuation of the agent (Case 2). There is rapid recurrence of injury with reexposure, often accompanied by fever.
Likelihood score: B (Highly likely cause of clinically apparent liver injury).

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Protein Binding
13-18%

[1]. Comprehensive kinetic analysis and influence of reaction components for chlorzoxazone 6-hydroxylation in human liver microsomes with CYP antibodies. Xenobiotica. 2015 Apr;45(4):353-360.

Chlorzoxazone is a member of the class of 1,3-benzoxazoles that is 1,3-benzoxazol-2-ol in which the hydrogen atom at position 5 is substituted by chlorine. A centrally acting muscle relaxant with sedative properties, it is used for the symptomatic treatment of painful muscle spasm. It has a role as a muscle relaxant and a sedative. It is a member of 1,3-benzoxazoles, an organochlorine compound and a heteroaryl hydroxy compound.
A centrally acting central muscle relaxant with sedative properties. It is claimed to inhibit muscle spasm by exerting an effect primarily at the level of the spinal cord and subcortical areas of the brain. (From Martindale, The Extra Pharmacopoea, 30th ed, p1202)
Chlorzoxazone is a Muscle Relaxant. The physiologic effect of chlorzoxazone is by means of Centrally-mediated Muscle Relaxation.
Chlorzoxazone is a centrally acting muscle relaxant commonly used for low back pain. Chlorzoxazone has been linked to rare instances of acute liver injury, a few of which have been fatal.
Chlorzoxazone is a benzoxazolone derivative with mild sedative and centrally-acting muscle relaxant activities. Although its exact mechanism of action is unknown, chlorzoxazone (CZ) appears to act at the spinal cord and subcortical levels of the brain to inhibit multisynaptic reflex arcs involved in producing and maintaining muscle spasms. This agent is extensively hydroxylated by cytochrome P450 2E1 (CYP2E1) to 6-hydroxychlorzoxazone (HCZ),11,12 which is subsequently glucuronidated and eliminated renally. Highly selective for CYP2E1, CZ may be used as a selective probe for phenotyping CYP2E1 in humans; the ratio of HCZ-to-CZ plasma concentrations obtained 2 to 4 hours after oral administration of CZ may be used as a phenotypic measure of CYP2E1 enzymatic activity.
A centrally acting central muscle relaxant with sedative properties. It is claimed to inhibit muscle spasm by exerting an effect primarily at the level of the spinal cord and subcortical areas of the brain. (From Martindale, The Extra Pharmacopoea, 30th ed, p1202)

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Drug Indication
For the relief of discomfort associated with acute painful musculoskeletal conditions.

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Mechanism of Action
Chlorzoxazone inhibits degranulation of mast cells, subsequently preventing the release of histamine and slow-reacting substance of anaphylaxis (SRS-A), mediators of type I allergic reactions. Chlorzoxazone also may reduce the release of inflammatory leukotrienes. Chlorzoxazone may act by inhibiting calcium and potassium influx which would lead to neuronal inhibition and muscle relaxation. Data available from animal experiments as well as human study indicate that chlorzoxazone acts primarily at the level of the spinal cord and subcortical areas of the brain where it inhibits multisynaptic reflex arcs involved in producing and maintaining skeletal muscle spasm

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Pharmacodynamics
Chlorzoxazone is a centrally-acting agent for painful musculoskeletal conditions. Data available from animal experiments as well as human study indicate that chlorzoxazone acts primarily at the level of the spinal cord and subcortical areas of the brain where it inhibits multisynaptic reflex a.c. involved in producing and maintaining skeletal muscle spasm of varied etiology. The clinical result is a reduction of the skeletal muscle spasm with relief of pain and increased mobility of the involved muscles.

C7H4CLNO2

169.56

168.993

95-25-0

Chlorzoxazone-d3;1185173-60-7;Chlorzoxazone-13C;616865-28-2

2733

White to off-white solid powder

1.5±0.1 g/cm3

336.9±34.0 °C at 760 mmHg

191-192 °C(lit.)

157.5±25.7 °C

0.0±0.8 mmHg at 25°C

1.674

2.29

1

2

0

11

185

0

TZFWDZFKRBELIQ-UHFFFAOYSA-N

InChI=1S/C7H4ClNO2/c8-4-1-2-6-5(3-4)9-7(10)11-6/h1-3H,(H,9,10)

5-chloro-3H-1,3-benzoxazol-2-one

5-Chloro-2-benzoxazolone; Paraflex; Chlorzoxazone

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ≥ 100 mg/mL (~589.73 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (14.74 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (14.74 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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 (Please use freshly prepared in vivo formulations for optimal results.)