Clinical Pharmacokinetics of the Salicylates

摘要: The use of salicylates in rheumatic diseases has been established for over 100 years. more recent recognition their modification platelet and endothelial cell function lead to other areas medicine. Aspirin (acetylsalicylic acid) is still the most commonly used salicylate. After oral administration as an aqueous solution aspirin rapidly absorbed at low pH stomach millieu. Less rapid absorption observed with formulations due rate limiting step tablet disintegration - this latter factor being maximal alkaline pH. dependent not only on formulation but also gastric emptying. follows first-order kinetics half-life ranging from 5 16 minutes. Hydrolysis salicylic acid by nonspecific esterases occurs liver and, a lesser extent, so that 68% dose reaches systemic circulation aspirin. Both are bound serum albumin (aspirin capable irreversibly acetylating many proteins), both distributed synovial cavity, central nervous system, saliva. approximately 20 fall concentration associated rise concentration. Salicylic renally excreted part unchanged elimination influenced urinary pH, presence organic acids, flow rate. Metabolism through glucuronide formation (to produce salicyluric acid), salicyl phenolic glucoronide), conjugation glycine oxidation gentisic acid. easily saturated concentrations described Michaelis-Menten kinetics. metabolic products follow dose-dependent; thus, larger employed, longer it will take reach steady-state. There evidence enzyme induction occurs. No significant differences exist between pharmacokinetics elderly or children when compared young adults. Apart free versus albumin-bound salicylate various disease states physiological conditions albumin, pharmacokinetic parameters patients rheumatoid arthritis, osteoarthritis, chronic renal failure essentially same.(ABSTRACT TRUNCATED AT 400 WORDS)