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Pharmacokinetics of salsalate and salicylic acid in normal and diabetic rats
Author(s) -
Cao Yanguang,
DuBois Debra C.,
Almon Richard R.,
Jusko William J.
Publication year - 2012
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.1797
Subject(s) - pharmacokinetics , bioavailability , dosing , diabetes mellitus , pharmacology , oral administration , medicine , distribution (mathematics) , absorption (acoustics) , endocrinology , chemistry , mathematical analysis , physics , mathematics , acoustics
ABSTRACT The pharmacokinetics (PK) of salsalate (SS) and salicylic acid (SA) was assessed in normal Wistar and diabetic Goto‐Kakizaki 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‐containing 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 (< 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‐diet feeding, the diabetic rats achieved lower blood concentrations of SA than normal rats with a higher apparent clearance ( CL / F ), possibly due to incomplete (47%) bioavailability. Such CL / F 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. Copyright © 2012 John Wiley & Sons, Ltd.