Abstracts

RATIONALE: Carbamazepine (CBZ) is a commonly prescribed antiepileptic drug. We are studying CBZ pharmacokinetics (PK) in young and elderly patients using an intravenous, stable-labeled CBZ formulation. This is a preliminary report on the safety and tolerability of the formulation.
METHODS: Adult patients ([gt] 18 years) with epilepsy without significant cardiac problems were enrolled. Patients on steady-state maintenance CBZ therapy were given a single 100 mg replacement dose of a 5H-dibenz[b,f]azepine-5-,13C, 15N-carboxamide (SL-CBZ) formulation as part of their daily regimen. The remainder of their daily doses was given orally. Blood pressure (BP) and heart rate (HR) data were collected prior to infusion, every 2 minutes during infusion, and every 15 minutes for the first hour following the completion of the infusion. Each subject was monitored by EKG before and during the infusion. The percent change in BP and HR was determined by subtracting the observation recorded at the end of infusion from the baseline observation. The mean and standard deviation were determined for all parameters. The study nurse monitored the infusion site for inflammation during the infusion and at the time that the indwelling catheter was removed. Patients were asked during the infusion if they were experiencing discomfort at the infusion site.
RESULTS: Seven younger (mean age 39 years: 3 female and 4 male) and one male elderly subject (70 years) have completed the study. CBZ daily doses ranged from 400-2400 mg. All subjects had a change in BP at the end of infusion of less than [plusminus]10% from baseline. The minimum and maximum BP and HR values were determined for each subject. The average percent change of the minimum recorded BP from baseline during infusion was [ndash]9.8% [plusminus] 8.1for systolic and [ndash]16% [plusminus] 17 for diastolic. The average percent change of the maximum recorded BP from baseline during infusion was + 9.8 [plusminus] 6.6 for systolic and +13 [plusminus] 19 for diastolic. The percent change of BP in all patients from end of infusion to baseline was -0.63% [plusminus] 6.5 for systolic and [ndash]1.9% [plusminus] 12 for diastolic. The average percent change in HR from end of infusion to baseline was 5.2% [plusminus] 14. The minimum and maximum observed BP or HR did not occur at the same time in each individual. One person reported transient light-headedness; no change in BP or HR was noted at that time point. No subject reported discomfort at the injection site. There was no evidence of inflamation at the site of infusion.
CONCLUSIONS: Our preliminary data indicate that this parenteral CBZ formulation can be safely administered to relatively healthy adult epilepsy patients.
[Supported by: NINDS P-50 NS16308 and MO1-RR0040]