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首页> 外文期刊>The Journal of pharmacy technology: jPT : official publication of the Association of Pharmacy Technicians >A Complex Interaction Between Clozapine and Phenytoin
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A Complex Interaction Between Clozapine and Phenytoin

机译：氯氮平与苯妥英钠之间的复杂相互作用

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Objective: As of July 9, 2004, to report the first case of potential pharmacodynamic and pharmacokinetic interactions between clozapine and phenytoin occurring simultaneously in a patient.Case Summary: A 60-year-old African American female treated with clozapine and phenytoin developed neutropenia after the clozapine dose was increased from 650 to 900 mg/day. The neutropenia resolved after phenytoin was discontinued, and the clozapine dose was decreased from 900 to 300 mg/day without any significant change in clozapine levels.Discussion: Neutropenia can be explained on the basis of a potential pharmacodynamic interaction between clozapine and phenytoin. However, neutropenia did not occur until the clozapine dose was increased from 650 to 900 mg/day, corresponding to an increase in clozapine levels from 90 to 114 ng/mL. Neutropenia resolved after phenytoin was discontinued, even though the clozapine concentrations achieved after phenytoin discontinuation (137 ng/mL) were almost the same as those when phenytoin was coadministered (114 ng/mL). This finding suggests that neutropenia was precipitated not only by an increase in the clozapine dose, but also by the concomitant use of phenytoin. On the other hand, the decrease in clozapine concentrations can be explained on the basis of a pharmacokinetic interaction between clozapine and phenytoin. Phenytoin has the potential to decrease clozapine concentrations by inducing the activity of CYP1A2, which provides a primary metabolic pathway for clozapine.Conclusions: Concomitant use of phenytoin may not only decrease clozapine concentrations and compromise its efficacy, but can also precipitate neutropenia. Although based on a single case report, these findings warrant caution when coadministering clozapine and phenytoin.
机译：目的：自2004年7月9日起，报告首例患者同时发生氯氮平和苯妥英钠之间潜在药效学和药代动力学相互作用的病例。病例摘要：一名接受氯氮平和苯妥英钠治疗的60岁非洲裔美国女性术后出现中性白细胞减少症氯氮平的剂量从650毫克/天增加到了900毫克/天。停用苯妥英钠后中性粒细胞减少，氯氮平剂量从900毫克/天减少至300毫克/天，氯氮平水平无明显变化。讨论：中性粒细胞减少症可以根据氯氮平和苯妥英之间潜在的药效相互作用来解释。但是，直到氯氮平的剂量从650毫克/天增加到900毫克/天才发生中性粒细胞减少症，这相当于氯氮平的水平从90纳克/毫升增加到114毫微克/毫升。苯妥英钠停用后中性粒细胞减少症得以缓解，即使苯妥英钠停用后达到的氯氮平浓度（137 ng / mL）与苯妥英钠并用时（114 ng / mL）几乎相同。这一发现表明，中性粒细胞减少症不仅通过氯氮平剂量的增加而沉淀，而且还伴随着苯妥英钠的使用。另一方面，氯氮平浓度的降低可以根据氯氮平和苯妥英之间的药代动力学相互作用来解释。苯妥英钠有可能通过诱导CYP1A2的活性而降低氯氮平的浓度，这为氯氮平提供了主要的代谢途径。结论：苯妥英钠的同时使用可能不仅会降低氯氮平的浓度并损害其疗效，而且还会引起中性粒细胞减少症。尽管基于单个病例报告，但联合使用氯氮平和苯妥英钠时，这些发现值得谨慎。

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