—An inverse relationship was demonstrable between the concentration of pyridoxal phosphate and the activity of pyridoxal kinase in rabbit brain. The administration of pyridoxine elevated the concentration of pyridoxal phosphate and decreased the activity of pyridoxal kinase. Conversely, the administration of deoxypyridoxine decreased the concentration of pyridoxal phosphate and increased the activity of pyridoxal kinase. The increase in the activity of pyridoxal kinase by deoxypyridoxine was blocked by actinomycin D or puromycin. These results were interpreted to indicate that the tissue availability of pyridoxal phosphate regulated the activity of pyridoxal kinase.

ExtractThis paper reports the differences in absorption and distribution in plasma of free and bound salicylate, and the differences in excretion of salicylic and salicyluric 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, the peak level of salicylic acid occurred in 4 h and the drug level returned to a base line at 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 I1 and 111) 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 counterpart (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). SpeculationPatients 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. Introductioncate that alterations occur in the activity of many enzymes [2,