Ahmed Ghada F, Bathena Sai Praneeth R, Brundage Richard C, Leppik Ilo E, Conway Jeannine M, Schwartz Janice B, Birnbaum Angela K
Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Room 463, 717 Delaware St., SE, Minneapolis, Minnesota, 55414, USA.
Center for Clinical and Cognitive Neuropharmacology, University of Minnesota, Minneapolis, Minnesota, USA.
AAPS J. 2017 Mar;19(2):551-556. doi: 10.1208/s12248-016-0022-z. Epub 2017 Jan 9.
Pharmacokinetic data of gabapentin (GBP) in community-dwelling elderly patients show a significant effect of advanced age on GBP pharmacokinetics due to altered renal function. However, there are no data in elderly nursing home (NH) patients to evaluate gabapentin absorption and elimination. Our objective was to characterize the pharmacokinetics of GBP in elderly nursing home patients maintained on GBP therapy. This was a prospective pharmacokinetic study in elderly nursing home patients (≥60 years) receiving GBP for the management of chronic pain or epilepsy from seven nursing homes. Pharmacokinetic parameters were estimated by nonlinear mixed-effects modeling. A one-compartment model described the data and clearance (CL) was associated with estimated glomerular filtration rate (eGFR) (p < 0.0001). The GBP CL in elderly nursing home patients was 2.93 L/h. After adjusting for the effect of GFR, GBP CL was not affected by age, sex, body weight, or comorbidity scores. No significant effects of body size measures, age, and sex were detected on volume of distribution. Dose-dependent bioavailability of GBP was demonstrated, and the saturable absorption profile was described by a nonlinear hyperbolic function. Prediction-corrected visual predictive check (pc-VPC) suggests adequate fixed- and random-effects models that successfully simulated the mean trend and variability in gabapentin concentration-time profiles. In this analysis, the parameters of the hyperbolic nonlinearity appear to be similar between elderly and younger adults.
加巴喷丁（GBP）在社区居住老年患者中的药代动力学数据显示，由于肾功能改变，高龄对GBP药代动力学有显著影响。然而，尚无老年疗养院（NH）患者的数据来评估加巴喷丁的吸收和消除情况。我们的目的是描述接受GBP治疗的老年疗养院患者中GBP的药代动力学特征。这是一项针对来自七家疗养院的接受GBP治疗慢性疼痛或癫痫的老年疗养院患者（≥60岁）的前瞻性药代动力学研究。通过非线性混合效应模型估计药代动力学参数。一个一室模型描述了数据，清除率（CL）与估计的肾小球滤过率（eGFR）相关（p < 0.0001）。老年疗养院患者的GBP CL为2.93 L/h。在调整GFR的影响后，GBP CL不受年龄、性别、体重或合并症评分的影响。未检测到体型测量、年龄和性别对分布容积有显著影响。证实了GBP的剂量依赖性生物利用度，饱和吸收曲线由非线性双曲线函数描述。预测校正视觉预测检查（pc-VPC）表明固定效应和随机效应模型足够，成功模拟了加巴喷丁浓度-时间曲线的平均趋势和变异性。在该分析中，老年和年轻成年人之间双曲线非线性的参数似乎相似。
