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

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.

Cerebral infarction and antiphospholipid syndrome in children.

OBJECTIVE: To investigate the prevalence of antiphospholipid antibodies (aPL) in children with acute cerebral infarction. METHODS: The study was carried out in 10 consecutive patients during the first days of neurological symptoms. aPL detected as lupus anticoagulant or anticardiolipin antibodies (aCL) and natural anticoagulant proteins C, S, and antithrombin III were determined in all patients. RESULTS: Seven patients had acute cerebral infarctions associated with aCL; 4 of these patients had high serum aCL concentrations in 2 different determinations (antiphospholipid syndrome). Two patients had temporary protein C deficiency. In one patient with negative aCL, protein C, S, and antithrombin III determinations were not carried out. No patient had evidence of connective tissue disease or family history of hypercoagulable state. After followup of 15.7 months, no patient had recurrent infarction while taking aspirin. CONCLUSION: Our study demonstrates high prevalence of aCL in children who suffer acute cerebral infarction and our results suggest aspirin may be effective therapy to prevent recurrences.

Successful treatment of transverse myelitis in a child with systemic lupus erythematosus.

We describe a 13-year-old female patient with systemic lupus erythematosus (SLE) who presented with acute transverse myelitis (ATM) in the course of SLE. IgG and IgM anticardiolipin antibodies (aCL) were positive at moderate titers. Magnetic resonance imaging (MRI) of the thoracic spine demonstrated decreased signal intensity and diffuse edema of the spinal cord from T2 to T6 on T1-weighted images. Dramatic clinical improvement of the neurologic impairment was noted a few days after high dose intravenous (IV) methylprednisolone (MP) and cyclophosphamide (Cy). Herein we further emphasize the benefit of IV MP and Cy in ATM and the relationship between ATM and antiphospholipid antibodies (aPLA) in SLE.