Groeneveld G J, van Kan H J M, Lie-A-Huen L, Guchelaar H-J, van den Berg L H
Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands.
Clin Pharmacol Ther. 2008 May;83(5):718-22. doi: 10.1038/sj.clpt.6100382. Epub 2007 Sep 26.
Patients with amyotrophic lateral sclerosis (ALS) who are treated with the antiglutamatergic drug riluzole receive a fixed-dose regimen of 50 mg b.i.d. The drug has been shown to increase tracheostomy-free survival by 3-6 months. The pharmacokinetics of riluzole show a high interindividual variability. Riluzole serum concentrations are associated with side effects and ALS symptoms, but the effect of the actual blood level of riluzole on disease progression and survival is unknown. We measured trough and peak serum concentrations of riluzole in 160 patients with ALS, and estimated the area under the curve for one dosage interval (AUCi) using a Bayesian method. We then determined the association between riluzole AUCi and survival over a 5-year period, and between riluzole AUCi and disease progression, defined by the rates of decline of arm strength and vital lung capacity. No significant association was found between riluzole AUCi and survival or disease progression.
接受抗谷氨酸能药物利鲁唑治疗的肌萎缩侧索硬化症（ALS）患者采用50毫克每日两次的固定剂量方案。已证明该药物可使无气管切开术的生存期延长3至6个月。利鲁唑的药代动力学显示个体间差异很大。利鲁唑血清浓度与副作用和ALS症状相关，但利鲁唑实际血药水平对疾病进展和生存期的影响尚不清楚。我们测量了160例ALS患者的利鲁唑谷浓度和峰浓度，并使用贝叶斯方法估算了一个给药间隔的曲线下面积（AUCi）。然后我们确定了利鲁唑AUCi与5年生存期之间的关联，以及利鲁唑AUCi与由手臂力量和肺活量下降率定义的疾病进展之间的关联。未发现利鲁唑AUCi与生存期或疾病进展之间存在显著关联。
