Abstracts

RATIONALE: Approximately 6% of all elderly nursing home residents receive phenytoin. Measurement of phenytoin concentrations are often performed to guide therapy; however, no large systematic evaluations of the variability of total phenytoin concentrations have been done. The goal of this project was to evaluate the intra-resident variability among multiple measurements of total phenytoin serum concentrations in nursing home residents.
METHODS: This study consisted of 54 residents who had at least three phenytoin concentrations measured while on the same dose of phenytoin for at least four weeks and who were not taking any interfering concomitant medications. These were a subset of 387 elderly nursing home residents from 112 nursing homes across the USA who had total phenytoin concentration measurements between June 1998 and December 2000. All changes in co-medications between serum concentration measurements were also examined and all highly protein bound ([gte]90% protein bound) were identified.
RESULTS: Subjects resided in 30 nursing homes in all regions of the United States: North Central States (27.8%), Pacific & Mountain States (53.7%), Southern States (14.8%), and Northeastern States (3.7%). The mean age was 80.1 years (range from 65-100 years) and 59.3% were female. The mean daily dose of total phenytoin concentrations per resident was 4.9 [plusminus] 1.5 mg/kg/day. The person with the smallest variability had a minimum concentration of 10.0 [mu]g/ml and a maximum of 10.4 [mu]g/ml. The person with the largest variability had a minimum concentration of 9.7 [mu]g/ml and a maximum of 28.8 [mu]g/ml. There were no unbound phenytoin concentration measurements in these residents. There was no trend towards higher or lower phenytoin concentrations over time. Sixteen subjects had data regarding serum albumin concentrations (mean: 3.5 [plusminus] 0.5) with 6 of the 16 having at least one serum albumin less than 3.2 gm/dl. Serum creatinine concentrations (mean: 0.89 [plusminus] 0.26 mg/dl) and BUN (mean: 23.4 [plusminus] 7.7 mg/dl) values were available on 40.7% of the residents.
CONCLUSIONS: Total phenytoin concentrations within an elderly nursing home resident varied 2-3 fold even though there was no change in dose. The variability observed in this study could not be explained by any one factor. These results have important clinical and public health implications considering the side effect profile of phenytoin, and the vulnerability of elderly nursing home residents. The findings of this study suggest that there may be considerable variability in the total phenytoin concentrations in the elderly nursing home resident and that measurement of a single total phenytoin concentration should not be used for determining dose changes.
[Supported by: NIH-NINDS P50-NS16308]