Methocarbamol metabolism

Most muscle relaxants are absorbed fairly easily from the gastrointestinal tract, and the oral route is the most frequent method of drug administration. In cases of severe spasms, certain drugs such as methocarbamol and orphenadrine can be injected intramuscularly or intravenously to permit a more rapid effect. Likewise, diazepam and dantrolene can be injected to treat spasticity if the situation warrants a faster onset. As discussed earlier, continuous intrathecal baclofen administration may be used in certain patients with severe spasticity, and local injection of botulinum toxin is a possible strategy for treating focal dystonias and spasticity. Metabolism of muscle relaxants is usually accomplished by hepatic microsomal enzymes and the metabolite or intact drug is excreted through the kidneys. 

After i.v. administration to horses, the clearance of methocarbamol from plasma is dose dependent lower clearance was calculated after higher doses were administered (Plumb 1995). The elimination half-life in horses (30 mg/kg) was 60-90 min. After oral administration, at dose rates of 50 and 100 mg/kg, peak plasma concentrations occurred within 15-45 min and the bioavailability was 51-124% (Muir et al 1984). Methocarbamol is metabolized to a dealkylated and a hydroxylated product. These two metabolites are found primarily as glucuronide and sulfate conjugates. Methocarbamol crosses both the placenta and the blood-brain barrier. 

Methocarbamol, USP. Methocarbamol. 3-(o-me-thoxyphcnoxy)-l.2-pn>panediol l-carbamate (Robaxin). is said to be more. sustained in effect than mephenesin. Likely sites for metabolic attack inciude the secondary hydroxyl group and the two ring positions opposite the ether functions. The dihydric parent compound, guaifenesin, is u.sed as an expectorant. 

I. Pharmacology. Methocarbamol is a centrally acting muscle relaxant. It does not directly relax skeletal muscle, and it does not depress neuromuscular transmission or muscle excitability muscle relaxation is probably related to its sedative effects. After intravenous administration, the onset of action is nearly immediate. Elimination occurs by hepatic metabolism, with a serum half-life of 0.9-2.2 hours. 

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

---