Influence of Renal Function on Pharmacokinetics of Antiepileptic Drugs Metabolized by CYP3A4 in a Patient With Renal Impairment
Influence of Renal Function on Pharmacokinetics of Antiepileptic Drugs Metabolized by CYP3A4 in a Patient With Renal Impairment
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DOI：
10.1097/ftd.0000000000000461
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发表时间：
2018-02-01
影响因子：
2.5
通讯作者：
Inoue, Yushi
中科院分区：
文献类型：
--
作者：
Yamamoto, Yoshiaki;Usui, Naotaka;Inoue, Yushi
背景：多项研究表明，肾脏损伤不仅会降低药物的肾脏清除率，还会降低药物对肝脏的清除量。方法：回顾计算1例伴有肾功能损害的癫痫患者的托吡酯和氯巴扎姆的浓度/剂量比(CD/Cd)。结果：1例额叶癫痫伴轻度肾损害患者服用苯妥英钠和3种细胞色素PYP3A4底物(托吡酯、氯巴坦和潘生丁)。随着肾损害程度的加重(Ccr：28.1mL/min)，托吡酯和氯巴坦的CD比率增加了约2倍。17例肾功能正常的苯妥英钠患者的平均CD比值为1740 6966 ng·mL(-1)·mg(-1)·kg(-1)。而肾损害患者(Ccr：20mL/min)的血药浓度比值明显高于对照组(范围5327~9113 ng.mL(-1).mg(-1).kg(-1))。结论：中重度肾损害患者在应用托吡酯、氯巴坦或潘生丁时，应根据药物监测进行剂量调整。
Background: Several studies have demonstrated that renal impairment not only decreases renal clearance but also hepatic clearance of medications that are CYP3A4 substrates. We evaluated the influence of renal function on the pharmacokinetics of antiepileptic drugs metabolized by CYP3A4.Methods: We retrospectively calculated the concentration/dose ratio (CD ratio) for topiramate and clobazam in an epilepsy patient with renal impairment. In addition, we determined the CD ratio of perampanel in 17 patients with normal renal function and compared it with that in the patient with renal impairment.Results: A patient with frontal lobe epilepsy and mild renal impairment [creatinine clearance (CCr): 67.7 mL/min] was taking phenytoin and 3 CYP3A4 substrates (topiramate, clobazam, and perampanel). With progression of renal impairment (CCr: 28.1 mL/min), the CD ratios of topiramate and clobazam increased by about 2-fold. The mean CD ratio of perampanel was 1740 6 966 ng.mL(-1).mg(-1).kg(-1) in the 17 patients with normal renal function using phenytoin. By contrast, the CD ratio of perampanel was markedly higher (range: 5327-9113 ng.mL(-1).mg(-1).kg(-1)) in the patient with renal impairment (CCr:,20 mL/min).Conclusions: These findings suggest that dose adjustment based on therapeutic drug monitoring is probably necessary when topiramate, clobazam, or perampanel is prescribed for patients with moderate-to-severe renal impairment.