Methocarbamol

The mechanism of action of methocarbamol in humans has not been established, but may be due to general CNS depression. It has no direct action on the contractile mechanism of striated muscle, the motor end plate or the nerve fiber.

Methocarbamol is a centrally acting muscle relaxant. Its muscle relaxing action is the result of the inhibition of polysynaptic reflexes in the spinal marrow and subcortical centres. Methocarbamol, at the therapeutic dose, does not affect the physiological tonus and contractility of the skeletal muscles as well as the motility of non-striated muscles, and has no action on the motor end plate.

Oral administration

After oral administration methocarbamol is absorbed quickly and completely. The active substance can be detected in blood already 10 minutes after intake and produces peak blood concentrations after 30-60 minutes.

Plasma half-life of methocarbamol is ca. 2 hours. Methocarbamol and its two metabolites are bound to glucuronic and sulfuric acid and are eliminated nearly exclusively via the kidneys. About half the dose administered is excreted into urine within 4 hours, only a small portion of which is eliminated as unchanged methocarbamol.

Renally impaired

The clearance of methocarbamol in renally-impaired patients on maintenance haemodialysis was reduced about 40% compared to a normal population, although the mean elimination half-life in these two groups was similar (1.2 versus 1.1 hours, respectively).

Hepatically impaired

In patients with cirrhosis secondary to alcohol abuse, the mean total clearance of methocarbamol was reduced approximately 70% compared to a normal population (11.9 L/hr), and the mean elimination half-life was extended to approximately 3.4 hours. The fraction of methocarbamol bound to plasma proteins was decreased to approximately 40 to 45% compared to 46 to 50% in an age and weight-matched normal population.

IV / IM administration

In healthy volunteers, the plasma clearance of methocarbamol ranges between 0.20 and 0.80 L/h/kg, the mean plasma elimination half-life ranges between 1 and 2 hours, and the plasma protein binding ranges between 46% and 50%.

Methocarbamol is metabolized via dealkylation and hydroxylation. Conjugation of methocarbamol also is likely. Essentially all methocarbamol metabolites are eliminated in the urine. Small amounts of unchanged methocarbamol also are excreted in the urine.

The acute toxicity of methocarbamol is comparatively low. Signs of intoxication in animal studies are ataxia, catalepsy, convulsions and coma.

Studies on chronic toxicity have not been performed.

Studies to determine a potential toxicity on reproduction have not been carried out.

In vitro and in vivo studies on genetic toxicity of methocarbamol did not reveal evidence of a mutagenic potential.

Long-term studies for evaluation of a carcinogenic potential have not been performed.