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首页> 外文期刊>The Canadian journal of hospital pharmacy. >Pharmacokinetic Interactions between Valproic Acid and Lorazepam (PIVOtAL Study): A Review of Site-Specific Practices
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Pharmacokinetic Interactions between Valproic Acid and Lorazepam (PIVOtAL Study): A Review of Site-Specific Practices

机译：丙戊酸和洛拉齐泮之间的药代动力学相互作用（关键研究）：对网站特定实践的综述

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Background: Coadministration of lorazepam and valproic acid is identified by tertiary references as causing a major drug interaction that requires therapy modification and dosage adjustments. The proposed mechanism involves inhibition of lorazepam glucuronidation via direct inhibition of uridine 5'-diphosphate-glucuronosyltransferase enzymes by valproic acid. However, the clinical significance of this interaction is unclear. Objectives: To identify site-specific practices and assess clinical responses to the interaction between valproic acid and lorazepam. Methods: A chart review was conducted for patients over 18 years of age who were admitted, from September 2008 to September 2014 inclusive, to the psychiatry or neurology service at Vancouver General Hospital, Vancouver, British Columbia, and who received concomitant valproic acid and lorazepam therapy. Results: Of the 30 patients included in the chart review, 12 (40%) received an intervention. A total of 8 (27%) patients experienced an adverse drug reaction (ADR), such as drowsiness and dizziness. Seven of these 8 patients were among those who received an intervention. The mean dosage (± standard deviation) of lorazepam was 4.2 ±1.2 mg per day among patients who experienced an ADR and less than 2 mg per day among those who did not experience an ADR. Conclusions: The current recommendation from tertiary drug references is to reduce the dose of lorazepam by 50% when this drug is coadminis-tered with valproic acid. However, this recommendation could not be validated through an analysis of patients exposed to this interaction in the clinical setting or through a review of the literature. Further clinical and pharmacokinetic studies are required to determine whether concurrent treatment with lorazepam and valproic acid should be considered as causing a major drug interaction. Until more data are available, clinicians should remain cognizant of the potential for a drug-drug interaction and should use the lowest effective dose of lorazepam when this drug is administered concomitantly with valproic acid.
机译：背景：罗西泮和丙戊酸的共同分析由第三次参考鉴定出需要治疗改性和剂量调整的主要药物相互作用。所提出的机制涉及通过直接抑制尿嘧啶5'-二磷酸葡糖醛糖基三转移酶的直接抑制洛拉西泮葡萄糖醛酸酯。然而，这种相互作用的临床意义尚不清楚。目的：鉴定特异性特异性实践，并评估对丙戊酸和洛拉西泮之间的相互作用的临床反应。方法：为18岁以上的患者进行了图表审查，从2008年9月到2014年9月到2014年9月，普及，不列颠哥伦比亚省温哥华综合医院（温哥华综合医院）的精神病学或神经病学服务，以及接受伴随的丙卓酸和洛拉西泮治疗。结果：在图表审查中包含的30名患者中，12名（40％）收到干预。共有8名（27％）的患者经历了不良药物反应（ADR），例如嗜睡和头晕。这8名患者中的七个是那些接受干预的人之一。洛拉齐泮的平均剂量（±标准偏差）每天为4.2±1.2mg，在没有经历ADR的人中每天经历ADR和每天少于2毫克的患者。结论：第三次药物参考的目前推荐是当该药物与丙戊酸共青酸化时，将洛拉西泮的剂量减少50％。但是，通过分析临床环境中暴露于这种互动的患者或通过对文献进行审查，无法通过分析来验证本建议书。需要进一步的临床和药代动力学研究来确定与洛拉西泮和丙戊酸的同时治疗是否应被认为是导致主要的药物相互作用。直到可用的更多数据，临床医生应继续认识到药物 - 药物相互作用的可能性，并且当该药物伴随着丙戊酸时，该药物应使用洛拉西泮的最低有效剂量。

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