Plasma levels of d-amphetamine in hyperactive children. Serial behavior and motor responses

Amphetamine has been clearly documented to be an efficacious treatment for hyperactive children. The pharmacokinetics of amphetamine have been studied in adults, but not in children. Sixteen male children who scored greater than 2SD from norms on Factors I and IV of Conner's Teacher Rating Scale and who were not excluded for reasons to do with medical or psychiatric conditions, intelligence, or age, had a plasma d-amphetamine apparent elimination half-life of 6.8 +/- 0.5h. Peak plasma level occurred between 3 and 4h (62.7 +/- 3.8 and 65.9 +/- 3.6 ng/ml, respectively). Six of these children had a repeat study and there were no significant differences within subject in apparent elimination half-lives and attained peak blood levels. The variation in plasma levels was greater during absorption than during elimination. Both behavioral and motor activity responses as analyzed by differences between amphetamine and placebo days (by paired t-tests) indicate significant responses between hours 1--4; however, these responses do not correlate with plasma amphetamine levels; they occur during the absorption phase. The decreased response to later similar plasma levels of d-amphetamine may be related to depletion of catecholamine stores, to replacement by a 'false neurotransmitter' metabolite of amphetamine, or to alteration in receptor sensitivity.