Abstracts

RATIONALE: The objective was to evaluate age differences in leviteracetam (LEV) doses and levels in a large clinical population. Age differences have been demonstrated for many antiepileptic drugs (AEDs). Preliminary data from registration studies suggested LEV doses needed to be higher in children and lower in elderly. This study was done to examine doses and concentrations in a large clinical practice evaluating for age effects.
METHODS: The MINCEP[reg] database of more than 2500 persons with epilepsy was searched for treatment with LEV. Concentration data was available for 470 individuals. Of these, 418 had dose data and 371 weights. Many patients had multiple visits and the highest doses were chosen for analysis. For analysis they were divided into three groups: [lte] 18 years, 19-64 years, and [gte] 65 years.
RESULTS: For the [lte]18 (n=29) the mean highest dose was 1993 mg/day or 32.8 mg/kg/day. For 19-64 (n=373) the mean highest dose was 2611.3 mg/day or 35.3 mg/kg/day. For [gte]0.93/I/kg/day (n=16) the mean highest dose was 1765.6 mg/day or 23.0 mg/kg/day. Corresponding LEV levels were 26.2[plusminus]15.1 ug/ml for [lte]18 (n=23); 29.6[plusminus]17.3ug/ml (n=335) for 19-64, and 24.7[plusminus]16.9 ug/ml for [gte]65 (n=13).
The mean highest dose for females was 2436 mg/day (range 250-7000) and for males was 2647 mg/day (range 275-5000). But in terms of mg/kg/day, the mean highest was 35.8 for females and 33.4 for males. Apparent clearance was calculated by dividing the daily dose in mg/kg by the level in ug/ml. For [lte]18 it was 1.25/l/kg/day; for 19-64 it was 1.19/l/kg/day; and for [gte]65 was 0.93/l/kg/day. Beacause of the wide variability, none of the differences were statistically significant.
CONCLUSIONS: The mean dose of LEV in this population was approximately 2500 mg per day, but the range was large. Although females received lower daily doses, their doses were higher than males on a mg/kg basis. The apparent clearance was greatest in persons less than 18 years of age and lowest in in those over 65(approximately 26% greater). It appears the concentrations of 29ug/ml with 1 SD of 17.2 are associated with the highest doses attained in a clinical setting and thus a range of 12 to 46 ug/ml could be considered effective for most persons with epilepsy.
[Supported by: MINCEP [reg] Epilepsy Care]; (Disclosure: Salary - 0, Grant - 0, Equity - 0, Consulting - 0, Ownership - 0, Materials - 0, Stock - 0, Royalties - 0, Honoraria - yes, Other - 0)