title: Stereoselective hepatic disposition of ibuprofen in the perfused liver of rat with adjuvant-induced arthritis.
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.
authors: a Department of Pharmacy , Faculty of Pharmacy, Kindai University , Higashi-osaka, Osaka , Japan.
authors: Misato
authors: M
authors: Uraki
authors: a Department of Pharmacy , Faculty of Pharmacy, Kindai University , Higashi-osaka, Osaka , Japan.
authors: Atsushi
authors: A
authors: Kawase
authors: a Department of Pharmacy , Faculty of Pharmacy, Kindai University , Higashi-osaka, Osaka , Japan.
authors: Masahiro
authors: M
authors: Iwaki
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism*; D001169:Arthritis, Experimental; D007052:Ibuprofen / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D051381:Rats; D013237:Stereoisomerism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D007052:Ibuprofen
keywords: Arthritis; chiral; ibuprofen; inflammation; perfusion; rat; stereoselectivity