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Xenobiotica
the fate of foreign compounds in biological systems
Volume 18, 1988 - Issue 6
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Original Article

A study of the relative hepatotoxicity in vitro of the non-steroidal anti-inflammatory drugs ibuprofen, flurbiprofen and butibufen

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Pages 737-745 | Published online: 30 Sep 2009
 

Abstract

1. The cytotoxic and metabolic effects of ibuprofen, flurbiprofen and butibufen have been studied in primary cultured hepatocytes. Toxic effects were observed for all three drugs at 10 times the therapeutic plasma concentration.

2. None of the drugs affected cell survival after 48 h of continuous exposure at their therapeutic plasma concentration, although significant increases of LDH leakage were detected.

3. Ibuprofen and butibufen were the most active in impairing gluconeogenesis from lactate (88% and 76% inhibition respectively) after 6h exposure at therapeutic plasma concentrations.

4. At 5 times therapeutic plasma concentrations, albumin synthesis was inhibited 40% (ibuprofen), 35% (flurbiprofen) and 100% (butibufen) after 6h exposure and significant effects were also observed after 24 h exposure.

5. Urea synthesis was inhibited 11% by butibufen at its therapeutic plasma concentration but only at higher concentrations by the other drugs.

6. Butibufen was potentially the most hepatotoxic drug as it has the highest therapeutic plasma concentration and had the lowest margin between therapeutic aiid toxic concentrations.

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