Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota.
Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, Minnesota.
Pharmacotherapy. 2017 Oct;37(10):1197-1203. doi: 10.1002/phar.2012. Epub 2017 Sep 19.
To characterize and quantify the variability of serial gabapentin concentrations in elderly patients with epilepsy.
This study included 83 patients (age ≥ 60 yrs) from an 18-center randomized double-blind double-dummy parallel study from the Veterans Affairs Cooperative 428 Study. All patients were taking 1500 mg/day gabapentin. Within-person coefficient of variation (CV) in gabapentin concentrations, measured weekly to bimonthly for up to 52 weeks, then quarterly, was computed. Impact of patient characteristics on gabapentin concentrations (linear mixed model) and CV (linear regression) were estimated.
A total of 482 gabapentin concentration measurements were available for analysis. Gabapentin concentrations and intrapatient CVs ranged from 0.5 to 22.6 μg/ml (mean 7.9 μg/ml, standard deviation [SD] 4.1 μg/ml) and 2% to 79% (mean 27.9%, SD 15.3%), respectively, across all visits. Intrapatient CV was higher by 7.3% for those with a body mass index of ≥ 30 kg/m (coefficient = 7.3, p=0.04). CVs were on average 0.5% higher for each 1-unit higher CV in creatinine clearance (coefficient = 0.5, p=0.03) and 1.2% higher for each 1-hour longer mean time after dose (coefficient = 1.2, p=0.04).
Substantial intrapatient variability in serial gabapentin concentration was noted in elderly patients with epilepsy. Creatinine clearance, time of sampling relative to dose, and obesity were found to be positively associated with variability.
描述并量化老年癫痫患者连续加巴喷丁浓度的变异性。
本研究纳入了来自退伍军人事务合作 428 研究的 18 个中心、随机、双盲、双模拟平行研究的 83 名（年龄≥60 岁）患者。所有患者均服用 1500mg/天的加巴喷丁。计算了每周至每 2 周测量一次、最长达 52 周、然后每季度测量一次的加巴喷丁浓度的个体内变异系数（CV）。使用线性混合模型估计患者特征对加巴喷丁浓度（线性混合模型）和 CV（线性回归）的影响。
共可分析 482 次加巴喷丁浓度测量值。加巴喷丁浓度和个体内 CV 范围分别为 0.5-22.6μg/ml（平均 7.9μg/ml，标准差[SD] 4.1μg/ml）和 2%-79%（平均 27.9%，SD 15.3%）。所有访视中，体质指数（BMI）≥30kg/m2 的患者个体内 CV 升高 7.3%（系数=7.3，p=0.04）。每增加 1 单位的肌酐清除率，CV 平均升高 0.5%（系数=0.5，p=0.03），每次剂量后平均时间延长 1 小时，CV 升高 1.2%（系数=1.2，p=0.04）。
在老年癫痫患者中，连续加巴喷丁浓度的个体内变异性很大。发现肌酐清除率、相对于剂量的采样时间和肥胖与变异性呈正相关。
