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首页> 外文期刊>Epilepsia: Journal of the International League against Epilepsy >Serum carbamazepine concentrations in elderly patients: a case-matched pharmacokinetic evaluation based on therapeutic drug monitoring data.
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Serum carbamazepine concentrations in elderly patients: a case-matched pharmacokinetic evaluation based on therapeutic drug monitoring data.

机译：老年患者的血清卡马西平浓度：基于治疗药物监测数据的病例匹配药代动力学评估。

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PURPOSE: To assess the influence of aging on the steady-state pharmacokinetics of carbamazepine (CBZ) in a large population of patients evaluated in a therapeutic drug monitoring (TDM) setting. METHODS: The database of a large TDM service was used to identify retrospectively steady-state serum CBZ concentrations in 157 elderly patients with epilepsy (65 years and older) treated with CBZ alone or in combination with phenobarbital (PB). CBZ apparent oral clearance (CL/F) values were calculated and compared with those determined in an equal number of controls aged 20 to 50 years, and matched for gender, body weight, and comedication. RESULTS: Compared with corresponding controls, mean CBZ CL/F values were 23% and 24% lower, respectively, in the groups of elderly patients receiving monotherapy (57.1 +/- 20.6 vs. 74.6 +/- 28.3 ml/h/kg; p < 0.0001) and PB comedication (74.7 +/- 25.5 vs. 98.7 +/- 34.9 ml/h/kg; p < 0.01). Within each age group, patients comedicated with PB showed significantly higher CBZ CL/F values than those on monotherapy. A negative correlation between CL/F and age was found both within the monotherapy and the PB comedicated groups. In addition, CL/F values showed a positive relation with the administered daily dosage, which persisted within subgroups homogeneous for age and comedication. The independent influence of age, CBZ dosage, and comedication on CBZ CL/F was confirmed by multiple regression analysis. CONCLUSIONS: CBZ CL/F is decreased in an age-dependent manner in elderly patients compared with younger subjects, presumably because a reduction in the rate of CYP3A4-mediated drug metabolism. Elderly patients retain their sensitivity to dose-dependent autoinduction and to heteroinduction by enzyme-inducing AEDs, but their metabolic rates remain considerably below those observed in matched controls. As a result of this, patients in old age will require lower CBZ dosages to achieve serum concentrations comparable with those found in nonelderly adults.
机译：目的：评估在治疗药物监测（TDM）设置中评估的大​​量患者中衰老对卡马西平（CBZ）稳态药代动力学的影响。方法：使用大型TDM服务数据库来回顾性分析157例单独使用CBZ或与苯巴比妥（PB）联合治疗的老年癫痫患者（65岁及以上）的稳态CBZ浓度。计算CBZ的表观口腔清除率（CL / F）值，并将其与在20至50岁的相同数量的对照组中确定的值进行比较，并根据性别，体重和喜剧进行匹配。结果：与相应对照组相比，接受单一疗法的老年患者组的平均CBZ CL / F值分别降低了23％和24％（57.1 +/- 20.6 vs. 74.6 +/- 28.3 ml / h / kg; p <0.0001）和PB喜剧（74.7 +/- 25.5 vs. 98.7 +/- 34.9 ml / h / kg; p <0.01）。在每个年龄组中，患有PB的患者的CBZ CL / F值均显着高于单一疗法的患者。在单药治疗和PB喜剧治疗组中，CL / F与年龄之间均呈负相关。此外，CL / F值与每日给药剂量呈正相关，该剂量在年龄和喜剧性均一的亚组中持续存在。多元回归分析证实了年龄，CBZ剂量和喜剧对CBZ CL / F的独立影响。结论：与年轻受试者相比，老年患者的CBZ CL / F以年龄依赖性方式降低，可能是因为CYP3A4介导的药物代谢速率降低。老年患者对剂量依赖性自动诱导和通过酶诱导的AED对异源诱导仍然保持敏感性，但是他们的代谢率仍远低于在对照中观察到的代谢率。结果，老年患者将需要较低的CBZ剂量以达到与非老年人相同的血清浓度。

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