Impact of cytochrome P450 inducers with or without inhibitors on the serum clobazam level in patients with antiepileptic polypharmacy
Impact of cytochrome P450 inducers with or without inhibitors on the serum clobazam level in patients with antiepileptic polypharmacy
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细胞色素P450诱导剂联合或不联合抑制剂对抗癫痫多重用药患者血清氯巴占水平的影响
DOI：
10.1007/s00228-014-1719-5
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Kagawa Y.
中科院分区：
文献类型：
--
作者：
Yamamoto Y;Takahashi Y;Imai K;Takahashi M;Nakai M;Inoue Y;Kagawa Y.
PurposeThe的目的是本研究的目的是评估的效果细胞色素P450（CYP 450）诱导剂/抑制剂的氯巴占（CLB）的药代动力学在接受抗癫痫multipharmacy.MethodsA从1,280例患者的常规治疗药物监测共2,504样本进行了回顾性审查。这些样本根据抗癫痫药物方案或年龄分组，然后计算浓度剂量（CD）比计算CLB的血清水平（ng/ml）除以剂量（mg/kg）以进行比较。（苯妥英钠（PHT）、卡马西平（CBZ）和苯巴比妥（PB）单独或联合用药）的比例比无诱导剂的患者低60.8%。在诱导剂中，使用PHT的患者的CD比率显著低于使用PB或CBZ的患者（p< 0.001）。当PHT与CBZ和/或PB组合时，没有观察到加和或协同作用。使用诱导剂的儿童患者的CLB CD比率比未使用诱导剂的患者低44.3%。无论儿童年龄如何，诱导剂的影响都没有变化，并且成人的影响比儿科患者更强。除诱导剂外，丙戊酸（VPA）可增加CD比率的降低，而同时使用司替戊醇可显著升高接受VPA的患者的CD比率。与此相反，CYP 3A 4底物，如唑尼沙胺和托吡酯，对CD比的CLB.ConclusionWe确定的CLB浓度的影响，CYP 3A 4诱导剂/抑制剂。我们的研究结果表明，临床相关的相互作用之间发生CLB和伴随抗癫痫药物。
PurposeThe aim of this study was to evaluate the effect of cytochrome P450 (CYP) inducers/inhibitors on the pharmacokinetics of clobazam (CLB) in patients receiving antiepileptic polypharmacy.MethodsA total of 2,504 samples obtained from 1,280 patients for routine therapeutic drug monitoring were retrospectively reviewed. These samples were grouped according to the antiepileptic drug regimens or age, and then the concentration to dose (CD) ratio (serum level (ng/ml) divided by dose (mg/kg)) of CLB was calculated for comparison.ResultsThe mean CD ratio of CLB in adult patients using enzyme inducers (phenytoin (PHT), carbamazepine (CBZ), and phenobarbital (PB) alone or in combination) was 60.8 % lower than the ratio in patients without inducers. Among the inducers, patients using PHT had a significantly lower CD ratio than patients using PB or CBZ (p< 0.001). When PHT was combined with CBZ and/or PB, no additive or synergetic interactions was observed. The CD ratio of CLB in pediatric patients using inducers was 44.3 % lower than in patients without inducers. The influence of inducers was unchanged regardless of the child’s age, and the effect was stronger in adults than in pediatric patients. Other than inducers, valproic acid (VPA) additively reduced the CD ratio, whereas concomitant use of stiripentol significantly elevated the CD ratio in patients receiving VPA. In contrast, CYP3A4 substrates, such as zonisamide and topiramate, had little influence on the CD ratio of CLB.ConclusionWe identified an impact of CYP inducers/inhibitors on the CLB concentration. Our findings demonstrated that clinically relevant interactions occur between CLB and concomitant antiepileptic drugs.
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DOI：
10.1002/j.1875-9114.2012.01028.x
发表时间：
2012-04
期刊：
Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy
影响因子：
--
作者：
M. Walzer;I. Bekersky;R. Blum;D. Tolbert
通讯作者：
M. Walzer;I. Bekersky;R. Blum;D. Tolbert
年龄和抗癫痫药物对氯巴扎姆和 N-去甲基氯巴扎姆血浆水平和动力学的影响。
DOI：
10.1111/j.1600-0773.1990.tb00799.x
发表时间：
1990
期刊：
Pharmacology & toxicology
影响因子：
--
作者：
H. Bun;S. Monjanel;F. Noel;A. Durand;J. Cano
通讯作者：
J. Cano
氯巴扎姆和标准抗癫痫药物在癫痫患者中的相互作用。
影响因子：
2.5
作者：
S. Sennoune;E. Mesdjian;J. Bonneton;P. Genton;C. Dravet;J. Roger
通讯作者：
J. Roger
CYP2C19 多态性和合并抗癫痫药物对癫痫患者血清氯巴占和 N-去甲基氯巴占浓度的影响
影响因子：
2.5
作者：
Yoshiaki Yamamoto;Yukitoshi Takahashi;K. Imai;K. Miyakawa;S. Nishimura;R. Kasai;H. Ikeda;R. Takayama;Y. Mogami;Tokito Yamaguchi;K. Terada;K. Matsuda;Y. Inoue;Y. Kagawa
通讯作者：
Y. Kagawa
影响因子：
3.9
作者：
Giraud, C;Treluyer, JM;Tran, A
通讯作者：
Tran, A