Research and Development, Teva Pharmaceutical Industries, Netanya, Israel.
Research and Development, Teva Pharmaceutical Industries, West Chester, PA, USA.
Headache. 2016 Sep;56(8):1300-9. doi: 10.1111/head.12895. Epub 2016 Jul 29.
To evaluate the safety, tolerability, and pharmacokinetics of sumatriptan delivered by the iontophoretic transdermal system (TDS) in adolescent patients.
Since nausea can be a prominent and early symptom of migraine, nonoral treatment options are often required. Sumatriptan iontophoretic TDS is approved for the acute treatment of migraine in adults. The present study evaluates the pharmacokinetics of sumatriptan administered via the iontophoretic TDS in adolescents, contrasting the findings with historical data from adults.
Patients aged 12-17 years (inclusive) with acute migraine were treated with sumatriptan iontophoretic TDS for 4 hours. Blood samples for pharmacokinetic profiling of sumatriptan were obtained prior to dosing and at predetermined time points covering the 12 hours postonset of treatment. Key pharmacokinetic endpoints included Cmax (peak plasma drug concentration), tmax (time to Cmax ), AUC0-∞ (area under the plasma concentration-time curve from time 0 to infinity), and t½ (terminal elimination half-life). Safety was evaluated by monitoring of adverse events in addition to laboratory and clinical assessments.
The sample consisted of 37 patients, and 36 were included in the PK evaluable population. Cmax , tmax , AUC0-∞ , and t½ values were all similar between male and female patients and between younger (12-14 years) and older (15-17 years) adolescents. When compared with historical adult data, adolescent patients demonstrated similar systemic exposures to those observed in adults (mean Cmax 20.20 (±6.43) ng/mL in adolescents vs 21.89 (±6.15) ng/mL in adults; mean AUC0-∞ 98.1 (±28.1) ng·h/mL in adolescents vs 109.7 (±26.1) ng·h/mL in adults). All adverse events were mild or moderate, with application-site paresthesia being the most common (32%). No clinically relevant changes in laboratory values, vital signs, or electrocardiogram findings were observed.
The iontophoretic TDS produced mean systemic exposures to sumatriptan in younger and older adolescents, in line with what was seen in adult subjects. It was generally well tolerated.
评估经皮离子导入系统（TDS）给予舒马曲坦用于青少年患者的安全性、耐受性和药代动力学。
由于恶心可能是偏头痛的突出且早期症状，因此通常需要非口服治疗选择。舒马曲坦离子导入 TDS 已批准用于成人偏头痛的急性治疗。本研究评估了经皮离子导入 TDS 给予舒马曲坦在青少年中的药代动力学，将研究结果与来自成人的历史数据进行对比。
年龄在 12-17 岁（含）之间的急性偏头痛患者接受舒马曲坦经皮离子导入 TDS 治疗 4 小时。在治疗开始后 12 小时内，在给药前和预定时间点采集用于舒马曲坦药代动力学分析的血样。主要药代动力学终点包括 Cmax（峰血浆药物浓度）、tmax（达峰时间）、AUC0-∞（从 0 时间到无穷大的血浆浓度-时间曲线下面积）和 t½（终末消除半衰期）。除了实验室和临床评估外，还通过监测不良事件来评估安全性。
样本包括 37 例患者，36 例患者纳入 PK 可评估人群。男性和女性患者之间以及较年轻（12-14 岁）和较年长（15-17 岁）青少年之间的 Cmax 、tmax 、AUC0-∞ 和 t½ 值均相似。与历史成人数据相比，青少年患者的全身暴露与成人观察到的暴露相似（青少年的平均 Cmax 为 20.20（±6.43）ng/mL，成人的平均 Cmax 为 21.89（±6.15）ng/mL；青少年的平均 AUC0-∞ 为 98.1（±28.1）ng·h/mL，成人的平均 AUC0-∞ 为 109.7（±26.1）ng·h/mL）。所有不良事件均为轻度或中度，以应用部位感觉异常最常见（32%）。未观察到实验室值、生命体征或心电图发现有临床相关变化。
经皮离子导入 TDS 在较年轻和较年长的青少年中产生了舒马曲坦的平均全身暴露，与在成年受试者中观察到的结果一致。它通常具有良好的耐受性。
