DISTRIBUTION AND METABOLISM OF METHOCARBAMOL

¹ Department of Physiology, Medical College of Virginia, Richmond, Virginia

Absorption, distribution, excretion and metabolism of methocarbamol in normal and pregnant dogs and in normal humans were investigated. In acute experiments on anesthetized dogs that received unlabeled or C¹⁴-metho-carbamol into a tied-off loop of the jejunum, C¹⁴ and chromogenous compounds related to methocarbamol distributed themselves widely in the body and crossed the placenta into the fetus. The kidneys and liver were the main routes of excretion. When the drug was given in relatively large doses, the concentration of methocarbamol and methocarbamol metabolites in tissues was higher than expected on the basis of simple diffusion equilibrium between blood (tissue fluid) and cell water. After treatment with C¹⁴-methocarbamol, the specific activity of the lipoids of several organs was only about one-third that of the dry lipoid-free residue of the same organs. At best, 84% of the C¹⁴ absorbed with the drug from the intestine could be recovered from urine, bile, blood and the main soft tissues.

In short-term experiments, some dogs received daily doses of unlabeled methocarbamol orally for 2 weeks. Chromogenous materials equivalent to less than 1% of the total methocarbamol dose were found in the chief soft tissues 1 day to 3 weeks after the drug was discontinued. When a single dose of C¹⁴-methocarbamol was given to other dogs, 50 to 90% of the activity appeared in the urine, and 10 to 12% in the feces on the first day.

Two human volunteers ingested methocarbamol for 3 consecutive days, during which quantitative urine collections were made. The urine was analyzed for chromogenous compounds before and after acid hydrolysis. When the results of the total 3-day urines were expressed as methocarbamol equivalents, less than 1% of the drug was detected before hydrolysis and about 10% after hydrolysis. Urinary excretion of chromogenous compounds ceased almost completely within 2 days after methocarbamol was discontinued.

Several types of studies were undertaken on dogs to clarify the metabolic fate of C¹⁴-metho-carbamol. In vivo hydrolysis of the carbarnate ester was negligible. Radioautographs of paper chromatograms gave evidence of six fractions, one of which was unchanged methocarbamol. Methocarbamol and two metabolites appeared as glucuronides in dog urine. Some of the metabolites of methocarbamol were not chloroform extractable from hydrolyzed and alkalinized urine.