The kinetic disposition of morphine was compared in 13 young and 7 older healthy subjects after a single intravenous dose of 10 mg/70 kg morphine. The apparent volume of distribution at steady state in elderly subjects was only half of that in young subjects. This difference was derived from reductions in both central and peripheral kinetic compartment volumes in the older subjects. The beta elimination phase for morphine was more rapid, but its plasma clearance was reduced in older subjects. Calculation of the peripheral compartment morphine concentration for these subjects indicated that drug concentration in this kinetic space was higher in older subjects for 1.5 hr after dosing.

The plasma concentrations and urinary excretion rates of salicylic acid (SA) and some of its metabolites (salicyluric acid [SUA] and acyl and phenolic glucuronide conjugates) were measured after an oral dose of acetylsalicylic acid to 44 healthy subjects of both sexes 20 to 78 years old. There was no change in the SA absorption rate, and plasma clearance of SA was not affected by age or sex. The volume of distribution increased with age in men but not in women. Plasma concentrations of SUA rose with age as the renal clearance of this metabolite fell. The kinetic parameters Km and Vmax for the SA-to-SUA reaction did not change with age; Vmax was significantly higher in women than in men. Urinary recovery of SA and its metabolites essentially accounted for the administered dose, and was little influenced by age or sex. We conclude that these factors play a minor role in the disposition of salicylate.

Loading and maintenance infusions of morphine sulfate were administered to 5 young male patients 23-34-yr-old prior to elective surgery. Apparent steady-state plasma concentrations were achieved 30 minutes after the start of the drug infusion. The volume of distribution at steady-state (2.43 +/- 0.48 L X kg-1), beta elimination rate constant (0.700 +/- 0.162/h) and plasma clearance (1.66 +/- 0.33 L X kg-1 X h-1) were similar to values previously determined in young healthy subjects receiving a single bolus infusion. These data confirm our findings concerning morphine disposition in healthy young subjects and demonstrate the feasibility of achieving predictable plasma concentrations of morphine for future assessment of pharmacodynamic/pharmacokinetic relationships for this drug.

The prognostic ability of global white matter and gray matter metabolite ratios following pediatric traumatic brain injury (TBI) and their relationship to 12-month neuropsychological assessments of intelligence quotient (IQ), attention, and memory is presented. Three-dimensional proton magnetic resonance spectroscopic imaging (MRSI) in pediatric subjects with complicated mild (cMild), moderate, and severe TBI was acquired acutely (6–18 days) and 12 months post-injury and compared to age-matched typically developing adolescents. A global linear regression model, co-registering MRSI metabolite maps with 3D high-resolution magnetic resonance images, was used to identify longitudinal white matter and gray matter metabolite ratio changes. Acutely, gray matter NAA/Cr, white matter NAA/Cr, and white matter NAA/Cho ratios were significantly lower in TBI groups compared to controls. Gray matter NAA/Cho was reduced only in the severe TBI group. At 12 months, all metabolite ratios normalized to control levels in each of the TBI groups. Acute gray matter and white matter NAA ratios were significantly correlated to 12-month assessments of IQ, attention, and memory. These findings suggest that whole brain gray matter and white matter metabolite ratios reflect longitudinal changes in neuronal metabolism following TBI, which can be used to predict neuropsychological outcomes in pediatric subjects.