THE METABOLISM OF CHLORPHENESIN CARBAMATE

¹ Biochemistry Research, The Upjohn Company, Kalamazoo, Michigan

The fate of orally administered chlorphenesin carbamate-H³ in the rat and the nonradioactive drug in the human has been studied. The drug was rapidly absorbed from the stomach of rats with about 81 to 88% of a single oral dose of 100 mg/kg appearing in the urine, the majority within 24 hours and only 5% in the feces.

The major metabolite in the rat, accounting for about 49% of the 24-hour urine radioactivity, was identified as a glucuronide of chlorphenesin carbamate. An additional 5.6% of the radioactivity was found as nonconjugated chlorphenesin carbamate and 3.9% as the sulfate conjugate. Some 17% of the urine radioactivity appeared in p-chlorophenoxyacetic acid which occurred in the urine primarily in the nonconjugated form, 9% as p-chlorophenol which was excreted mainly as the sulfate conjugate and 5% as p-chlorophenoxylactic acid. Smaller quantities of an unknown neutral metabolite and several unknown acidic metabolites were also detected. Upon prolonged administration or with larger single doses of the drug, the relative distribution of urinary metabolites was altered.

In man, about 85% of an oral dose of nonradioactive chlorphenesin carbamate was excreated within 24 hours in the urine as the glucuronide conjugate. Only a small quantity of the drug was converted to p-chlorophenoxylacetic acid, p-chlorophenoxyacetic acid and p-chlorophenol.