CLINICAL-PHARMACOLOGY OF OXICAMS - NEW INSIGHTS INTO THE MECHANISMS OF THEIR DOSE-DEPENDENT TOXICITY

Six oxicams, sudoxicam, isoxicam, piroxicam, tenoxicam, meloxicam and lornoxicam, were compared in an attempt to understand why, despite clo se chemical structures, two of them were associated with an increased risk of toxicity in patients. Different factors have been revealed whi ch may explain these differences. A weak association constant to human serum albumin (HSA), together with a high plasma concentration, favou rs a rapid increase in unbound concentration (C-u) when total plasma c oncentration rises (peak of absorption). Pathological states may enhan ce this increase when both HSA plasma concentration is decreased and f ree fatty acid concentrations are increased. However, the main cause o f toxicity may be the existence in some subjects of HSA natural mutant s whose ability to bind oxicams is markedly lower than normal.