{"title":"双氢麦角胺药代动力学、临床疗效和恶心之间的关系--综述。","authors":"Richard B Lipton, John A Kollins, Detlef Albrecht","doi":"10.1111/head.14877","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>To assess the relationships between dihydroergotamine (DHE) pharmacokinetic (PK) parameters, clinical efficacy, and nausea incidence to determine a DHE PK profile that optimizes efficacy while minimizing adverse events (AEs), particularly nausea.</p><p><strong>Background: </strong>Dihydroergotamine is a widely used option for the acute treatment of migraine. Although multiple DHE dosage forms, with varying PK and AE profiles, have been evaluated in randomized controlled trials (RCTs), the relationships between PK profile, efficacy, and the common DHE-related AE, nausea, have not been comprehensively evaluated.</p><p><strong>Methods: </strong>A literature search identified RCTs evaluating the efficacy (2-h pain relief [2hPR]) of different DHE dosage forms. The PK profiles for these DHE dosage forms were determined from published literature. Univariate regression analyses were performed to determine the PK parameters that best predicted 2hPR across DHE dosage forms. The relationship between maximum plasma concentration (C<sub>max</sub>) and nausea incidence for various dosage forms was determined from published Phase 1 trials.</p><p><strong>Results: </strong>The literature search identified nine RCTs with DHE dosage forms that reported 2hPR: DHE liquid nasal spray (four studies), DHE administered subcutaneously (three), and DHE administered via oral pulmonary inhalation (two). The DHE PK parameters that best predicted 2hPR rates were C<sub>max</sub> and area under the curve from time zero to 0.5 h post-dose (AUC<sub>0-0.5h</sub>) (R<sup>2</sup> = 0.59 for each). Across Phase 1 trials, nausea incidence was minimal when C<sub>max</sub> was <2500 pg/mL but increased in a log-linear manner when C<sub>max</sub> exceeded ~2500 pg/mL.</p><p><strong>Conclusions: </strong>The maximum concentration and AUC over the first 30 min following DHE administration were associated with increasing rates of 2hPR and a C<sub>max</sub> below ~2500 pg/mL was associated with low incidences of nausea. We suggest that this may be an optimal profile for a DHE delivery form. Further research to test this hypothesis is warranted.</p>","PeriodicalId":12844,"journal":{"name":"Headache","volume":" ","pages":"527-535"},"PeriodicalIF":5.4000,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11884232/pdf/","citationCount":"0","resultStr":"{\"title\":\"Relationship of dihydroergotamine pharmacokinetics, clinical efficacy, and nausea-A narrative review.\",\"authors\":\"Richard B Lipton, John A Kollins, Detlef Albrecht\",\"doi\":\"10.1111/head.14877\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>To assess the relationships between dihydroergotamine (DHE) pharmacokinetic (PK) parameters, clinical efficacy, and nausea incidence to determine a DHE PK profile that optimizes efficacy while minimizing adverse events (AEs), particularly nausea.</p><p><strong>Background: </strong>Dihydroergotamine is a widely used option for the acute treatment of migraine. Although multiple DHE dosage forms, with varying PK and AE profiles, have been evaluated in randomized controlled trials (RCTs), the relationships between PK profile, efficacy, and the common DHE-related AE, nausea, have not been comprehensively evaluated.</p><p><strong>Methods: </strong>A literature search identified RCTs evaluating the efficacy (2-h pain relief [2hPR]) of different DHE dosage forms. The PK profiles for these DHE dosage forms were determined from published literature. Univariate regression analyses were performed to determine the PK parameters that best predicted 2hPR across DHE dosage forms. The relationship between maximum plasma concentration (C<sub>max</sub>) and nausea incidence for various dosage forms was determined from published Phase 1 trials.</p><p><strong>Results: </strong>The literature search identified nine RCTs with DHE dosage forms that reported 2hPR: DHE liquid nasal spray (four studies), DHE administered subcutaneously (three), and DHE administered via oral pulmonary inhalation (two). The DHE PK parameters that best predicted 2hPR rates were C<sub>max</sub> and area under the curve from time zero to 0.5 h post-dose (AUC<sub>0-0.5h</sub>) (R<sup>2</sup> = 0.59 for each). Across Phase 1 trials, nausea incidence was minimal when C<sub>max</sub> was <2500 pg/mL but increased in a log-linear manner when C<sub>max</sub> exceeded ~2500 pg/mL.</p><p><strong>Conclusions: </strong>The maximum concentration and AUC over the first 30 min following DHE administration were associated with increasing rates of 2hPR and a C<sub>max</sub> below ~2500 pg/mL was associated with low incidences of nausea. We suggest that this may be an optimal profile for a DHE delivery form. 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引用次数: 0
摘要
研究目的评估双氢麦角胺（DHE）药动学（PK）参数、临床疗效和恶心发生率之间的关系，以确定一种既能优化疗效，又能减少不良事件（AEs），尤其是恶心发生率的双氢麦角胺PK曲线：背景：二氢麦角胺是一种广泛用于偏头痛急性期治疗的药物。尽管随机对照试验（RCTs）已对具有不同 PK 和 AE 特征的多种 DHE 剂型进行了评估，但尚未对 PK 特征、疗效和常见的 DHE 相关 AE（恶心）之间的关系进行全面评估：方法：通过文献检索确定了评估不同 DHE 剂型疗效（2 小时疼痛缓解 [2hPR]）的 RCT。从已发表的文献中确定了这些 DHE 剂型的 PK 曲线。进行了单变量回归分析，以确定最能预测不同 DHE 剂型 2hPR 的 PK 参数。从已发表的 1 期试验中确定了各种剂型的最大血浆浓度（Cmax）与恶心发生率之间的关系：文献检索发现了九项报告了 2hPR 的 DHE 剂型 RCT：DHE液体鼻腔喷雾剂（四项研究）、DHE皮下注射剂（三项）和DHE口腔肺部吸入剂（两项）。最能预测 2hPR 率的 DHE PK 参数是 Cmax 和从零时到给药后 0.5 小时的曲线下面积（AUC0-0.5h）（两者的 R2 均为 0.59）。在整个 1 期试验中，当 Cmax 最大值超过约 2500 pg/mL 时，恶心发生率极低：结论：DHE 给药后 30 分钟内的最大浓度和 AUC 与 2hPR 发生率的增加有关，而 Cmax 低于 ~2500 pg/mL 与恶心发生率低有关。我们认为这可能是 DHE 给药形式的最佳特征。我们需要进一步研究来验证这一假设。
Relationship of dihydroergotamine pharmacokinetics, clinical efficacy, and nausea-A narrative review.
Objective: To assess the relationships between dihydroergotamine (DHE) pharmacokinetic (PK) parameters, clinical efficacy, and nausea incidence to determine a DHE PK profile that optimizes efficacy while minimizing adverse events (AEs), particularly nausea.
Background: Dihydroergotamine is a widely used option for the acute treatment of migraine. Although multiple DHE dosage forms, with varying PK and AE profiles, have been evaluated in randomized controlled trials (RCTs), the relationships between PK profile, efficacy, and the common DHE-related AE, nausea, have not been comprehensively evaluated.
Methods: A literature search identified RCTs evaluating the efficacy (2-h pain relief [2hPR]) of different DHE dosage forms. The PK profiles for these DHE dosage forms were determined from published literature. Univariate regression analyses were performed to determine the PK parameters that best predicted 2hPR across DHE dosage forms. The relationship between maximum plasma concentration (Cmax) and nausea incidence for various dosage forms was determined from published Phase 1 trials.
Results: The literature search identified nine RCTs with DHE dosage forms that reported 2hPR: DHE liquid nasal spray (four studies), DHE administered subcutaneously (three), and DHE administered via oral pulmonary inhalation (two). The DHE PK parameters that best predicted 2hPR rates were Cmax and area under the curve from time zero to 0.5 h post-dose (AUC0-0.5h) (R2 = 0.59 for each). Across Phase 1 trials, nausea incidence was minimal when Cmax was <2500 pg/mL but increased in a log-linear manner when Cmax exceeded ~2500 pg/mL.
Conclusions: The maximum concentration and AUC over the first 30 min following DHE administration were associated with increasing rates of 2hPR and a Cmax below ~2500 pg/mL was associated with low incidences of nausea. We suggest that this may be an optimal profile for a DHE delivery form. Further research to test this hypothesis is warranted.
期刊介绍：
Headache publishes original articles on all aspects of head and face pain including communications on clinical and basic research, diagnosis and management, epidemiology, genetics, and pathophysiology of primary and secondary headaches, cranial neuralgias, and pains referred to the head and face. Monthly issues feature case reports, short communications, review articles, letters to the editor, and news items regarding AHS plus medicolegal and socioeconomic aspects of head pain. This is the official journal of the American Headache Society.
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