Absorption, Distribution and Excretion
The absolute bioavailability of metaxalone from Skelaxin tablets is not known.
Metaxalone is metabolized by the liver and excreted in the urine as unidentified metabolites.
800 L
68 +/- 50 L/h [Subjects received 1×400mg tablet under fasted conditions]
66 +/- 51 L/h [Subjects received 2×400 mg tablets under fasted conditions]
Although plasma protein binding and absolute bioavailability of metaxalone are not known, the apparent volume of distribution (V/F ~ 800 L) and lipophilicity (log P = 2.42) of metaxalone suggest that the drug is extensively distributed in the tissues. Metaxalone is metabolized by the liver and excreted in the urine as unidentified metabolites.
Peak plasma concentrations of metaxalone occur approximately 3 hours after a 400 mg oral dose under fasted conditions. Thereafter, metaxalone concentrations decline log-linearly with a terminal half-life of 9.0 + or - 4.8 hours. Doubling the dose of skelaxin from 400 mg to 800 mg results in a roughly proportional increase in metaxalone exposure as indicated by peak plasma concentrations (Cmax) and area under the curve (AUC). Dose proportionality at doses above 800 mg has not been studied. The absolute bioavailability of metaxalone is not known

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Metabolism / Metabolites
Probably hepatic.
Biotransformations...studied in dogs and in man. 5-(3-methyl-5-carboxyphenoxymethyl)-2-oxazolidinone, major metabolite, is excreted in urine and feces; this also occurs in urine as ester glucuronide. Fission of ether linkage...affords...3,5-xylenol and 5-hydroxymethyloxazolidinone. Oxazolidinone ring is stable in mammals.
Yields 5-(5-carboxy-3-methylphenoxymethyl)-2-oxazolidone in man & in dogs, yields 3,5-dimethylphenol in man and in dogs. /From table/
Metaxalone is metabolized by the liver and excreted in the urine as unidentified metabolites.

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Biological Half-Life
9.2 (+/- 4.8) hours
Terminal half-life /is/ 9.0 + or - 4.8 hours

Hepatotoxicity
According to the product brochure, metaxalone may cause jaundice, although there are no specific case reports of hepatotoxicity from metaxalone in the literature and no prospective trials with routine monitoring of aminotransferase levels. Given its long history, metaxalone appears to be without significant hepatotoxicity.
Likelihood score: E (Unlikely cause of clinically apparent liver injury).
Drug Class: Muscle Relaxants

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Interactions
Additive CNS depression may occur when metaxalone is administered concomitantly with other CNS depressants, including alcohol. If metaxalone is used concomitantly with other depressant drugs, caution should be used to avoid overdosage.

https://en.wikipedia.org/wiki/Metaxalone

Metaxalone is an aromatic ether.
Metaxalone is a moderate to strong muscle relaxant used in the symptomatic treatment of musculoskeletal pain caused by strains, sprains, and other musculoskeletal conditions. It is marketed by King Pharmaceuticals under the brand name Skelaxin®. Its main mechanism of action is thought to involve general central nervous system depression. Metaxalone is associated with few side effects and is available as a 800 mg scored tablet.
Metaxalone is a Muscle Relaxant. The physiologic effect of metaxalone is by means of Centrally-mediated Muscle Relaxation.
Metaxalone is a centrally acting skeletal muscle relaxant that has been in use for more than 40 years. Metaxalone has not been associated with serum aminotransferase elevations during therapy or with clinically apparent hepatic injury.
Metaxalone has been reported in Caenorhabditis elegans with data available.
Metaxalone is an oxazolidinone with centrally-acting skeletal muscle relaxant properties. Although the exact mechanism through which metaxalone exerts its effect is largely unknown, it might be due to general central nervous system (CNS) depression. Metaxalone has no direct effect on the contractile mechanisms of striated muscle, the motor end plate, or the nerve fiber.

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Drug Indication
For the treatment of painful peripheral musculoskeletal conditions and spasticity from upper motor neuron syndromes.
FDA Label

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Mechanism of Action
The mechanism of action of metaxalone in humans has not been established, but may be due to general central nervous system depression.
Metaxalone is a CNS depressant that has sedative and skeletal muscle relaxant effects. The precise mechanism of action of the drug is not known. The skeletal muscle relaxant effects of orally administered metaxalone are minimal and are probably related to its sedative effect. The drug does not directly relax skeletal muscle and, unlike neuromuscular blocking agents, does not depress neuronal conduction, neuromuscular transmission, or muscle excitability.
The mechanism of action of metaxalone in humans has not been established, but may be due to general central nervous system depression. Metaxalone has no direct action on the contractile mechanism of striated muscle, the motor end plate or the nerve fiber.

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Therapeutic Uses
Metaxalone is used as an adjunct to rest, physical therapy, analgesics, and other measures for the relief of discomfort associated with acute, painful musculoskeletal conditions. /Included in US product label/

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Drug Warnings
The most frequent adverse effects of metaxalone are drowsiness, dizziness, headache, nervousness or irritability, nausea, vomiting, and GI upset. Other adverse effects include confusion, anorexia, dry mouth, and urinary retention. Exacerbation of tonic-clonic (grand mal) seizures has also been reported.
Hypersensitivity reactions and rash (with or without pruritus) have occurred in patients receiving metaxalone. Anaphylactoid reactions, leukopenia, hemolytic anemia, and jaundice have occurred rarely. Abnormalities in liver function tests, such as increased serum concentrations of AST (SGOT), ALT (SGPT), alkaline phosphatase, and bilirubin, and increased sulfobromophthalein (BSP) retention and thymol turbidity, have occurred in patients receiving metaxalone. Although a causal relationship to metaxalone has not been established, nephrotoxicity and proteinuria have occurred rarely during treatment with the drug; pyuria and nephrolithiasis have also been reported.
Safety and efficacy of metaxalone in children 12 years of age or younger have not been established; therefore, the drug should not be administered to children in this age group.
Patients should be warned that metaxalone may impair ability to perform hazardous activities requiring mental alertness or physical coordination, such as operating machinery or driving a motor vehicle. In addition, patients should be warned that additive CNS depression may occur when the drug is administered concomitantly with other CNS depressants, including alcohol. Metaxalone should be used with caution in geriatric patients and in patients with hepatic or renal impairment. Liver function studies should be performed periodically during metaxalone therapy in patients with preexisting liver damage. The drug is contraindicated in patients with substantially impaired hepatic or renal function, known hypersensitivity to the drug or any ingredient in the formulation, or a history of drug-induced, hemolytic, or other anemias.
For more Drug Warnings (Complete) data for METAXALONE (8 total), please visit the HSDB record page.

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Pharmacodynamics
Metaxalone is a skeletal muscle relaxant indicated as an adjunct to rest, physical therapy, and other measures for the relief of discomforts associated with acute, painful musculoskeletal conditions. The mode of action of this drug has not been clearly identified, but may be related to its sedative properties. Metaxalone does not directly relax tense skeletal muscles in man.

C12H15NO3

221.2524

221.105

1665-48-1

Metaxalone-d3;1192812-66-0;Metaxalone-d6;1189944-95-3

15459

White to almost white crystalline powder
Crystals from ethyl acetate

1.1±0.1 g/cm3

453.6±14.0 °C at 760 mmHg

121-123ºC

228.2±20.1 °C

0.0±1.1 mmHg at 25°C

1.525

2.42

1

3

3

16

247

0

O1C(N([H])C([H])([H])C1([H])C([H])([H])OC1C([H])=C(C([H])([H])[H])C([H])=C(C([H])([H])[H])C=1[H])=O

IMWZZHHPURKASS-UHFFFAOYSA-N

InChI=1S/C12H15NO3/c1-8-3-9(2)5-10(4-8)15-7-11-6-13-12(14)16-11/h3-5,11H,6-7H2,1-2H3,(H,13,14)

5-[(3,5-dimethylphenoxy)methyl]-1,3-oxazolidin-2-one

AHR438; NSC170959; AHR-438; NSC-170959; AHR 438;NSC 170959 Metaxalone; Skelaxin; Methaxalonum; Metaxalon; Zorane; AHR 438; 3B2-1432; I06-0370;

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 (~451.98 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (11.30 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 (11.30 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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Solubility in Formulation 3: ≥ 2.5 mg/mL (11.30 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 corn oil and mix evenly.

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