Influence of nutritional status on the pharmacokinetics of acetylsalicylic acid and its metabolites in children with autoimmune disease

Abstract

Background: It is unknown whether nutritional status associated with autoimmune disease alters the pharmacokinetics of acetylsalicylic acid (ASA) and its metabolites. Objective: We studied the effects of the nutritional status of children with autoimmune disease on the disposition of ASA and its metabolites. Design: A prospective, open-label study was performed with 21 children aged 3-15 y who required ASA therapy. Children received 25 mg ASA/kg orally. Blood samples were drawn before and 0.5, 1.0, 2.0, 4.0, 8.0, 12.0, and 24.0 h after ASA administration; urine samples were collected at different intervals. ASA and its metabolites were measured in plasma and urine. Nutritional status was assessed previously. Results: The ASA maximum plasma concentration, area under the curve, and total clearance were significantly lower in underweight children than in normal-weight children. The elimination rate constants of gentisic acid (GA), salicyluric acid (SUA), and salicylic acid (SA) in plasma were slower for underweight children than for normal-weight children. The distribution volume of SUA increased significantly (r = 0.92) when the deficit percentage in weight-for-height increased. Underweight children excreted less GA and SA, but more SUA, than did normal-weight children. Conclusions: These observations suggest a decrease in the hydrolysis and oxidative reactions of the metabolic pathway of ASA and its metabolites,: in underweight children. The study illustrates the need for pharmacokinetic data to establish the individual doses of drugs, particularly in conditions that alter nutritional status.