Metabolism of salsalate in normal subjects.

The metabolism of salsalate (I) was characterized in two normal volunteers. The drug was almost completely absorbed and was excreted primarily in the urine; only approximately 1% of the total dose was found in the stools. Although I is a salicylate derivative, which on hydrolysis yields two molecules of salicylic acid (II), approximately 7-10% of the dose was not hydrolyzed to salicylic acid and appeared in the urine either as unchanged drug or glucuronide conjugates. Thus, the incomplete availability of salicylate from salsalate that has been previously reported may not be due to incomplete absorption of the drug but to incomplete hydrolysis to salicylic acid.