Cirrhosis ibuprofen

Acetyls alley lie acid was shown to prevent cirrhosis under certain experimental conditions [125]. Naproxen and indomethacin partially protected against LPS and D-galactosamine-in-duced hepatotoxicity [126] Acetylsalicylic acid and ibuprofen were also protective in endo-toxic shock [127]. Endotoxaemia is one of the complications in cirrhotic patients [128] and is probably caused by an impaired ability of the liver to take up and detoxify gut-derived LPS [116]. The presence of portosystemic shunts in cirrhotic patients may also contribute to this spill-over of LPS into the systemic circulation [129]. NSAIDs, however, are also reported to provoke deleterious effects on renal function in cirrhosis [130], and can therefore not be used in cirrhotic patients. Cell-specific delivery of NSAIDs to SECs and/or KCs may make application of these drugs in cirrhosis feasible by circumventing the renal side-effects. 

A later single-dose study in eight patients with moderate to severe cirrhosis and a PT of 2-5 seconds above the npper limit of normal, showed an approximate doubling of the half-life compared to controls. Metabolic inversion of the inactive R-ibuprofen to the active S-ibupro-fen may also be impaired in hepatic cirrhosis, because the AUC ratio of R- to S-ibuprofen was significantly higher in patients with cirrhosis. Medicinal ibuprofen is supplied as a racemic mixture [39]. 

Li G, Treiber G, Maier K, et al. (1993) Disposition of ibuprofen in patients with liver cirrhosis. Clin Pharmacokinet 25 154-163. 

---