Stereoselective hepatic disposition of ibuprofen in the perfused liver of rat with adjuvant-induced arthritis. (2nd November 2017)

• Record Type: Journal Article
• Authors: Uraki, Misato; Kawase, Atsushi; Iwaki, Masahiro
• Is Part Of: Xenobiotica. Volume 47:Number 11(2017)
• Page Start: 943
• Page End: 950
• Publication Date: 2017-11-02
• Subjects: Arthritis -- chiral -- ibuprofen -- inflammation -- perfusion -- rat -- stereoselectivity; Metabolism -- Periodicals; Drugs -- Physiological effect -- Periodicals; Food additives -- Periodicals; Chemicals -- Physiological effect -- Periodicals; Biochemistry -- Periodicals; Pharmaceutical Preparations -- metabolism -- Periodicals; Metabolism -- Periodicals; 574.133
• DOI: 10.1080/00498254.2016.1252869
• Languages: English
• ISSNs: 0049-8254

Abstract

Abstract: 1. The effects of adjuvant-induced arthritis (AA) on the stereoselective hepatic disposition and chiral inversion of "profens" have scarcely been investigated. Ibuprofen (IB) undergoes unidirectional chiral inversion from R -IB to S -IB and is metabolized to IB-glucuronide (IB-Glu). 2. We used an in situ perfused rat liver system to clarify the effects of inflammation on the metabolic activities and chiral inversion of IB without protein binding. 3. After dosing of R -IB, AA had minimal effect on the elimination of R -IB from the perfusate. Larger amounts of S -IB-Glu than R -IB-Glu were observed in the bile at the dose of 2.4 and 4.8 μmol. However, after dosing of S -IB, the elimination of S -IB from the perfusate in AA rats was delayed, indicating a significant decrease in the hepatic clearance in AA rats. The cumulative biliary excretion of S -IB-Glu in AA rats was promoted after dosing with S -IB. There was little difference between the chiral inversion ratios of the control and AA rats. 4. The present study demonstrated that AA results in the delayed elimination of S -IB, the active form, without changes to the chiral inversion ratio. Thus, further attention to the altered stereoselective pharmacokinetics of IB during inflammation is required.