In this study we evaluated subjects with
Down's syndrome for the possibility that direct or indirect gene dosage effects of
trisomy 21 alter the fate of
acetaminophen. We also investigated the usefulness of noninvasive sampling techniques to obtain parameter estimates for
drug disposition in these developmentally disabled individuals. After administration of 5 mg/kg and 20 mg/kg oral doses of
acetaminophen, subjects with
Down's syndrome resembled control subjects in most pharmacokinetic and metabolic parameters, including apparent half-life, volume of distribution per kilogram body mass, total body clearance per kilogram of body mass, extrapolated saliva concentration at time zero, and the urinary excretion of
acetaminophen glucuronide and
sulfate conjugates.
Glutathione conjugation tended to increase and
sulfate conjugation tended to decrease in all subjects as the
acetaminophen dose increased from 5 mg/kg to 20 mg/kg. Results based on these samples of very limited size also suggest that
acetaminophen metabolism to
glutathione-derived conjugates may have been increased in subjects with
Down's syndrome. The similarity of estimates of
acetaminophen pharmacokinetics and data on metabolic fate between subjects with
Down's syndrome and normal volunteers indicates that large effects of
trisomy 21 on these processes are unlikely. Also, these results were in agreement with extensive data obtained with invasive techniques, indicating that simple noninvasive methodologies appear to be well suited for studying
acetaminophen disposition in populations of developmentally disabled individuals.