Alteration in metabolism of acetylsalicylic acid in children with Down's syndrome: decreased plasma binding and formation of salicyluric acid.

Abstract

Extract: This paper reports the differences in absorption and distribution in plasma of free and bound salicylate, and the differences in excretion of salicylic and salicyuric acid in the urine of children with Down's syndrome and in control subjects. After oral administration of a single dose of acetylsalicylic acid (35 mg/kg) to normal children, the peak level of salicylic acid in plasma occurred in 2 h and the drug level returned to the base line at approximately 8 h; in children with Down's syndrome, th peak level of salicylic acid occurred in 4 h and the drug level returned to a base line at a approximately 16 h. In children with Down's syndrome, the 24-h excretion of salicylate metabolites in the urine indicated a higher level of free salicylic acid (table I) and a lower level of salicyluric acid (tables II and III) when compared with the control group. Although the concentration of salicylate is small in erythrocytes, children with Down's syndrome showed a higher level when compared with their normal counter part (table IV). The in vitro plasma-binding studies indicated that in comparison with normal subjects, children with Down's syndrome were less capable of binding salicylate (table V). Speculation: Patients with Down's syndrome are a highly abnormal group of individuals because of their morphological, physiological and biochemical aberrations. They are directed and influenced by their abnormalities, one manifestation of which is altered pharmacogenetics. It should be expected that any therapeutic regime must take these differences into consideration and dosage must be calculated not on the basis of body weight but according to the plasma level of the drug or of its active metabolites.