Abstracts

RATIONALE: At the end of this activity the participant will understand the rationale of pharmacokinetic dynamics in neonates and will be able to apply this understanding toward use of either Phenobarbital or phenytoin in neonatal seizures
MATERIALS AND METHODS
Chemicals.
Phenobarbital, phenytoin and methyl phenobarbital were obtained from Sigma Chemical Corporation (St. Louis, Mo). Isotopically labeled phenobarbital [2- 15N,13C-phenobarbital] and isotopically labeled phenytoin [2- 13C-1, 3 15N-phenytoin].
RESULTS: Based on calculations obtained from the labeled analogue only, peak plasma levels of labeled phenytoin appeared 4 to 6 hours after oral administration and varied from 1.4 to 3.7 mg/L. For the purpose of illustration one representative plot from a patient who received labeled phenytoin is shown in Figure 5. Using a semilogrithmic scale the t1/2 of labeled phenytoin was calculated as the time required for change in drug concentration by fifty percent.
Similar methods were used to calculate the t1/2 in patients receiving maintenance phenobarbital.
DISCUSSION
In this study we were able to enroll nine neonates between 25 and 40 weeks gestational age. Four neonates received one half of the calculated 24-hour maintenance dose of unlabeled phenytoin intravenously along with one half of the maintenance dose orally as labeled phenytoin. This constituted between 12 and 23% peak enrichment of the phenytoin body pool with labeled analogue. Of the four patients in this study at these doses, variability in t1/2 (11-16 hours) was much narrower than that reported in previous literature as 3 to 140 hours (8, 9, 10, 11).
Five neonates received an oral labeled Phenobarbital dose.Conventional pharmacokinetic approaches to obtain these data would have demanded achievement of steady state, single dose administration, or cessation of therapy. This data was obtained without altering the medically indicated therapeutic regimen or assuming the presence of steady state[table1].