“…NSAIDs with low pKa values (e.g. carboxylic acids) have a greater tendency to be irritant to the gastric mucosa as a consequence of their selective absorption into GI mucosal cells (Brune et al, 1977;Rainsford and Brune, 1978;Rainsford et al, 1981Hotz-Behofsits et al, 2003;Rainsford, 1999a;Sigthorsson et al, 2000aSigthorsson et al, , 2000b leading to ion trapping (Brune et al, 1977;Rainsford and Brune, 1978;Rainsford et al, 1981Sigthorsson et al, 2000), as well as uptake into mitochondria and Gastrointestinal (GI) adverse events remain the main concern in the use of NSAIDs and GI tolerability is a central issue for clinicians who prescribe these drugs (Rainsford, 1996(Rainsford, , 2001Rothstein, 1998). Other important side effects should also be taken into consideration when prescribing these drugs such as allergic reactions, skin adverse reaction, renal complications, alteration of hepatic enzyme levels and rarely hepatopathies (Rainsford, 1996(Rainsford, , 1997(Rainsford, , 2001Rothstein, 1998;Teoh and Farrell, 2003;Uemura et al, 2003;Simon and Namazy, 2003;Sanchez-Borges et al, 2002McGettigan et al, 2000).…”