{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,15]],"date-time":"2026-02-15T08:44:46Z","timestamp":1771145086316,"version":"3.50.1"},"reference-count":18,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2012,7,26]],"date-time":"2012-07-26T00:00:00Z","timestamp":1343260800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biopharm &amp; Drug Disp"],"published-print":{"date-parts":[[2012,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>The pharmacokinetics (PK) of salsalate (SS) and salicylic acid (SA) was assessed in normal Wistar and diabetic Goto\u2010Kakizaki rats. Three PK studies were conducted: (1) PK of SA in normal rats after intravenous dosing of SA at 20, 40, 80 mg\/kg. (2) PK of SS and SA in normal rats after oral dosing of SS at 28, 56, 112 mg\/kg. (3) PK during 4 months feeding of SS\u2010containing diet in both normal and diabetic rats. The disposition of SS and SA were evaluated simultaneously using a pharmacokinetic model comprising several transit absorption steps and linear and nonlinear dual elimination pathways for SA. The results indicated that the nonlinear elimination pathway of SA only accounted for a small fraction of the total clearance (&lt; 12%) at therapeutic concentrations. A flat profile of SA was observed after oral dosing of SS, particularly at a high dose. The possible reasons for this flat profile were posed. During the SS\u2010diet feeding, the diabetic rats achieved lower blood concentrations of SA than normal rats with a higher apparent clearance (<jats:italic>CL<\/jats:italic>\/<jats:italic>F<\/jats:italic>), possibly due to incomplete (47%) bioavailability. Such<jats:italic>CL<\/jats:italic>\/<jats:italic>F<\/jats:italic>decreased with age in both diabetic and normal rats. The effect of diabetes on SA pharmacokinetics may necessitate increased dosing in the future usage of SS in diabetes. 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