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Naratriptan is a novel 5-HT1 agonist developed to treat acute migraine. The study objective was to characterize the pharmacokinetics of oral naratriptan in adolescent migraine patients outside a migraine attack. Subjects received a single 2.5 mg naratriptan tablet. Serial serum samples for naratriptan concentrations were collected over 24 hours. Blood pressure, pulse rate, and 12-lead ECG were recorded at baseline and at regular intervals after dosing. Seven patients--3 males and 4 females, 12 to 16 years of age--received drug and completed the study. The geometric mean and 95% confidence interval maximum concentration (Cmax) was 8.0 ng/mL (5.9-10.7), elimination half-life (t1/2) was 4.9 hours (4.5-5.4), area under the concentration-time curve (AUC) was 74.6 ng.h/mL (56.6-98.2), and apparent total clearance (Cl/F) was 558.8 mL/min (424.3-735.9). The median time to maximal concentration (tmax) was 4 hours, with a range of 1.5 to 4. Blood pressure, pulse rate, and ECG parameters did not change significantly from baseline. No serious adverse events or subject withdrawal after drug administration occurred. Oral naratriptan pharmacokinetic parameters in adolescents were similar to values reported in adults. Naratriptan doses for adolescents older than 12 years of age would be expected to be similar to adult doses.

The purpose of this study was to determine if phenytoin protein binding and metabolism were altered in prepubescent pediatric patients within the first 10 days following severe, acute traumatic brain injury. Patients (n = 10) received phenytoin loading doses (15-20 mg/kg) followed by a maintenance regimen (7 mg/kg/day) initiated within 12 hours of the loading dose. Phenytoin serum concentrations were measured serially on days 1, 2, 3, 5, 7, 9, and 10 at 1, 6, and 12 hours. Time-invariant and time-variant Michaelis-Menten pharmacokinetic models were fit to the unbound phenytoin concentration-time data (ADAPT II). Albumin concentrations significantly decreased over time (p < 0.001) and were predictive of the phenytoin binding ratio (r2 = 0.373, p < 0.0001). The time-variant model provided a superior fit of the data in 7 patients with no difference between models in 3 patients. Rapid inhibition of metabolism (Vmaxbaseline = 2.82 +/- 2.35 mg/kg/day) was observed initially following injury. This was followed by induction of metabolism as reflected by a Vmaxinduced of 20.79 +/- 13.71 mg/kg/day, which was approximately twofold higher than reported values for nonstressed children. Children with severe, acute neurotrauma were found to have markedly altered protein binding and phenytoin metabolism.

Down syndrome (DS) is a common cause of mental retardation resulting from trisomy 21. Previous reports have described altered pharmacokinetics and pharmacodynamics in patients with DS. The authors report six cases of infants (2-19 months) with DS who demonstrated altered theophylline pharmacokinetics. Clearance was prolonged in most of these patients. No overt toxicity to theophylline was noted in any of the cases. The authors propose that patients with DS are at increased risk for altered theophylline pharmacokinetics. The etiology for altered pharmacokinetics of theophylline may be due to the interface between normal developmental changes and pharmacogenetic differences associated with DS and/or the secondary disease states and concomitant drug therapy.

The negative inotropic and chronotropic effects of beta-blocker therapy have been reported to reduce morbidity and mortality in patients with Marfan syndrome; however, little is known about the pharmacokinetics of atenolol after oral administration of multiple doses to patients with the Marfan syndrome. We studied the pharmacokinetics of atenolol in 13 such patients aged 18.7 +/- 2.9 years who were receiving 1.78 +/- 0.58 mg/kg/day (70.1 +/- 20.3 mg/m2/day) of atenolol for 6 weeks or longer. Mean +/- SD percentage change in baseline heart rate after the administration of atenolol was -18.03 +/- 16.59% and mean +/- SD percentage change in exercise heart rate after atenolol was -33.22 +/- 14.75% (P < .01). Six to 8 atenolol serum concentrations were collected in each patient during a 12-hour dosing interval and were determined by high-performance liquid chromatography with ultraviolet detection. Serum atenolol concentrations at 0 (123 +/- 70 micrograms/L) and 12 (116 +/- 66 micrograms/L) hours were within 20% of each other and were thus assumed to be at steady-state. A one-compartment, steady-state pharmacokinetic model with first-order absorption and elimination was fitted to the concentration-time data for each patient using nonlinear regression. Maximal concentration was 343 +/- 120 micrograms/L, and the mean half-life was 4.72 hours.(ABSTRACT TRUNCATED AT 250 WORDS)

We point out the connection between electronic monitoring and repeated screening tests, and suggest a flexible and practical method to determine the efficacy of monitoring devices and new technologies. We point out the benefits of the Mantel-Haenszel estimator of an odds ratio for determining diagnostic test indices. From estimates of sensitivities and specificities, we produce receiver operating characteristic (ROC) curves to compare the performance of two or more monitoring devices in a clinical setting.

Animal data and anecdotal human experience suggest that vascular damage induced by the infusion of dextrose/amino acid solutions may be ameliorated by the concomitant administration of fat emulsion. We prospectively evaluated the effect of the continuous infusion of peripheral nutrition solutions with and without fat emulsion on the incidence of, probability of, and time to infiltration of peripheral venous lines in infants (median age: 1.0 month; range 1 day-11.9 months). Ninety-seven peripheral venous lines were studied in 53 infants who received 10% dextrose (n = 34), 10% dextrose/2% amino acids (n = 30), or 10% dextrose/2% amino acids/fat emulsion (n = 33). Solutions were administered by positive pressure infusion devices through Teflon catheters with similar gauge. Dextrose, amino acid, electrolyte, and mineral content was standardized for the dextrose/amino acid and dextrose/amino acid/fat emulsion groups. The three groups were similar with respect to age, race, gender, weight, administration of intravenous medications, and catheter site (p greater than 0.05). Patients receiving dextrose/amino acid or dextrose/amino acid/fat emulsion had greater rates of solution administration than those receiving dextrose alone (p less than 0.002). Infiltration occurred in 71% of dextrose, 66% of dextrose/amino acid, and 67% of dextrose/amino acid/fat emulsion solutions (p greater than 0.05). The probability of infiltration was greater for infants receiving dextrose/amino acid than for those receiving either dextrose or dextrose/amino acid/fat emulsion (p = 0.01). The mean +/- SEM length of time the intravenous sites were viable was significantly shorter for the dextrose/amino acid solutions (26.3 +/- 3.3 hr) compared to the dextrose (54.9 +/- 7.8 hr) and dextrose/amino acid/fat emulsion (43.6 +/- 4.2 hr) groups. No site complications were associated with the infiltration of any solution. We conclude that the incidence of infiltration among the three solution groups studied is not different. However, the time to infiltration is prolonged and the probability of infiltration is decreased following the infusion of either dextrose alone or dextrose/amino acid/fat emulsion solutions when compared to the administration of dextrose/amino acid solutions without concomitant fat emulsion infusion.