Abstracts

Rationale: The incidence of epilepsy increases with advanced age, and the use of antiseizure drugs (ASDs) is high in nursing homes (NH).The elderly may have substantial physiological changes that alter pharmacokinetics (PK) and pharmacodynamics. Significant intra-individual variability (IIV) in some ASDs in elderly NH individuals has been already reported. The aim of this study is to evaluate the IIV among multiple measurements of total gabapentin (GBP), levetiracetam (LEV), and total and unbound phenytoin (PHT) concentrations in elderly NH residents. Methods: This was a prospective study of elderly (≥ 65 years) NH residents from five nursing homes located in Minnesota and California who were taking GBP, LEV or PHT as part of their clinical care (November 2007 – December 2013). Inclusion criteria were: (1) residing in a NH for ≥2 months; (2) receiving GBP, LEV or PHT; (3) being on the same dose of GBP, LEV or PHT for at least four weeks. Blood samples were collected at approximately 4 weeks apart and concentrations were measured via LCMS. All samples from one individual were measured on the same analytical run to decrease assay variability. Information on demographics, dosing frequency, and co-medications were abstracted from records. Doses and serum concentrations were presented as mean (standard deviation (SD)). For each ASD, IIV was expressed as the coefficient of variation (CV %), calculated as standard deviation/average x 100 (%) from all the drug concentration measurements of each individual. The CV for each ASD was compared using a one-way ANOVA (Turkey-Kramer) (p<0.05). Statistical analysis was performed in IBM SPSS Statistics version 25 (SPSS Inc, Chicago, IL, U.S.A). Results: Of the 123 NH residents identified, 52 taking GBP (73.1% females), 21 taking LEV (66.7% females) and 12 taking PHT (41.7% females) met inclusion criteria. The mean (SD) daily dose was 788.46 (687.04) mg/day, 1313.25 (739.61) mg/day and 343.69 (121.75) mg/day, for GBP, LEV and PHT, respectively. The total number of blood concentrations available was 215 (4-6 per patient) for GBP, 83 (3-4 per patient) for LEV, 51 (3-6 per patient) for total PHT, and 40 (3-6 per patient) for unbound PHT concentrations. Table 1 summarizes the mean (SD) blood concentrations by ASD. For all three ASDs, some subjects had low IIV (as little as 3.47% for LEV), while it was high for others (98.34% for GBP). Percentage of subjects with an IIV greater than 30% was 28.85% for GBP, 23.81% for LEV, and 8.33% and 50% for total and unbound PHT, respectively. There was no significant difference between means of IIV of the different ASDs (p>