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接受视频脑电图监测的癫痫患者中拉莫三嗪的药代动力学评估。

Lamotrigine pharmacokinetic evaluation in epileptic patients submitted to VEEG monitoring.

作者信息

Almeida A M, Falcão A C, Sales F, Baldeiras I, Rocha M J, Caramona M M

机构信息

Laboratory of Pharmacology, Faculty of Pharmacy, University of Coimbra, Largo D. Dinis, 3000-295 Coimbra, Portugal.

出版信息

Eur J Clin Pharmacol. 2006 Sep;62(9):737-42. doi: 10.1007/s00228-006-0144-9. Epub 2006 Jul 27.

Abstract

OBJECTIVE

The aim of the present study was to evaluate the pharmacokinetic profile of lamotrigine (LTG) in epileptic patients submitted to video-electroencephalography (VEEG) monitoring and, in addition, to investigate the influence of concomitant antiepileptic drugs (AEDs) on the kinetics of LTG.

METHODS

The analysis assumed a one-compartment open model with first-order absorption and elimination. The kinetic estimates obtained in this population were validated by using the Prediction-Error approach. The influence of medication was also assessed by the calculation of the LTG concentration-to-dose ratio. Patients (n=135) were divided into four groups according to the co-medication: Group 1, patients taking LTG with enzyme-inducer agents; Group 2, patients receiving LTG with valproic acid; Group 3, patients receiving both inducers and inhibitors of LTG metabolism; Group 4, patients under AEDs not known to alter LTG metabolism.

RESULTS

The obtained estimates for clearance (CL) (L/h/kg) [0.075+/-0.029 (Group 1), 0.014+/-0.005 (Group 2), 0.025+/-0.008 (Group 3) and 0.044+/-0.011 (Group 4)] appear to be the most appropriate set to be implemented in clinical practice as prior information, as demonstrated by the accuracy and precision of the measurements. In addition, the influence of co-medication on the LTG profile was further confirmed by the basal LTG concentration-to-dose ratio.

CONCLUSION

The results of the present investigation may contribute to achieving the goal of optimizing patients' clinical outcomes by managing their medication regimen through measured drug concentrations. Patients submitted to VEEG monitoring may benefit from this study, as the results may be used to provide better drug management in this medical setting.

摘要

目的

本研究旨在评估接受视频脑电图(VEEG)监测的癫痫患者中拉莫三嗪(LTG)的药代动力学特征,并研究联合使用抗癫痫药物(AEDs)对LTG动力学的影响。

方法

分析采用具有一级吸收和消除的单室开放模型。通过预测误差法验证该人群中获得的动力学估计值。还通过计算LTG浓度与剂量之比评估药物的影响。根据联合用药情况将患者(n = 135)分为四组:第1组,服用LTG与酶诱导剂的患者;第2组,接受LTG与丙戊酸的患者;第3组,接受LTG代谢诱导剂和抑制剂的患者;第4组,使用已知不会改变LTG代谢的AEDs的患者。

结果

获得的清除率(CL)(L/h/kg)估计值[第1组为0.075±0.029,第2组为0.014±0.005,第3组为0.025±0.008,第4组为0.044±0.011]似乎是临床实践中作为先验信息实施的最合适的一组,测量的准确性和精密度证明了这一点。此外,联合用药对LTG曲线的影响通过基础LTG浓度与剂量之比得到进一步证实。

结论

本研究结果可能有助于通过根据测量的药物浓度管理患者的用药方案来实现优化患者临床结局的目标。接受VEEG监测的患者可能会从本研究中受益,因为研究结果可用于在这种医疗环境中提供更好的药物管理。

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