影响韩国成年癫痫患者常规治疗药物监测中血清托吡酯浓度的因素。

Factors influencing serum topiramate concentrations in routine therapeutic drug monitoring in Korean adult patients with epilepsy.

机构信息

Department of Laboratory Medicine & Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

出版信息

Ther Drug Monit. 2013 Apr;35(2):177-82. doi: 10.1097/FTD.0b013e31827efe1d.

DOI:10.1097/FTD.0b013e31827efe1d

PMID:23503443

Abstract

PURPOSE

Topiramate (TPM) is a broad-spectrum anticonvulsant used both as an adjunctive treatment and as monotherapy. In this study, the results from a routine therapeutic drug monitoring (TDM) service for TPM are summarized. In addition, factors influencing the variability in serum concentration of TPM and the effects of comedication on serum TPM concentration were investigated.

METHODS

Serum measurements of TPM from a routine TDM database were analyzed retrospectively. Concentration-to-dose ratio (CDR) was calculated to assess pharmacokinetic variability. We compared CDRs for patients receiving TPM monotherapy and patients receiving TPM with other antiepileptic drugs, together with the effects of each comedication on TPM concentration were studied.

RESULTS

There were 510 samples from 476 adult patients. Serum TPM was below 2.0 mg/L or above 10.0 mg/L in 28.2% and 5.9% of samples, respectively. Although serum TPM was broadly related to prescribed dose, there was wide variation. Most patients using TPM were treated in combination with other anticonvulsants (90.8%). TPM-CDR in patients receiving TPM monotherapy was not significantly different from those receiving TPM in combination with nonenzyme inducers, but TPM-CDR was lower in patients who were taking inducers (P < 0.0001, Kruskal-Wallis test, Dunnett method).

CONCLUSIONS

A large interindividual variability in TPM serum concentrations was observed in this cohort of patients. TDM of TPM is useful in selected patients such as those suspected of poor compliance/absorption and those who may experience pharmacokinetic changes because of comedication or physiological changes.

摘要

目的

托吡酯（TPM）是一种广谱抗惊厥药，既作为辅助治疗药物，也作为单药治疗药物。本研究总结了常规治疗药物监测（TDM）服务中 TPM 的结果。此外，还研究了影响 TPM 血清浓度变异性的因素以及合并用药对 TPM 血清浓度的影响。

方法

回顾性分析常规 TDM 数据库中的 TPM 血清测量值。计算浓度-剂量比（CDR）以评估药代动力学变异性。我们比较了接受 TPM 单药治疗和接受 TPM 联合其他抗癫痫药物治疗的患者的 CDR，并研究了每种合并用药对 TPM 浓度的影响。

结果

共有 476 例成年患者的 510 个样本。血清 TPM 低于 2.0mg/L 或高于 10.0mg/L 的样本分别占 28.2%和 5.9%。尽管血清 TPM 与处方剂量广泛相关，但仍存在很大的变异性。大多数使用 TPM 的患者都与其他抗惊厥药联合治疗（90.8%）。接受 TPM 单药治疗的患者的 TPM-CDR 与联合使用非酶诱导剂的患者无显著差异，但服用诱导剂的患者的 TPM-CDR 较低（P<0.0001，Kruskal-Wallis 检验，Dunnett 法）。