Background

Vasovagal syncope is a common cause of syncope which, if recurrent, can have multiple negative consequences such as injury and occupational disability. Various medications can be used to decrease the recurrence of vasovagal syncope but there are no drugs that can be used by patients to interrupt a perceived vasovagal episode.

Methods

A phase I study was performed to evaluate the tolerability and safety of a gel formulation containing capsaicin (1 mg), phenylephrine HCL (PE) and caffeine citrate (200 mg) (CPC) in normal adult volunteers. Secondary objectives were to characterize the pharmacokinetics (PK) of the CPC formulation and the highest dose of PE needed to achieve a target increase in systolic BP of at least 40 mmHg. After receiving the first dose, a second dose of the CPC mixture was administered at 2 h. Suboptimal changes in systolic blood pressure (SBP) were noted at PE doses of 0.6, 1.2, and 1.8 mg, therefore a second cohort was studied at PE doses of 10, 20, and 30 mg. Blood samples were collected in rapid sequence and were assayed for all three drugs.

Results

A total of 17 subjects received the drug with no serious adverse effects reported. All doses were well tolerated, although the capsaicin content usually caused expected temporary oral and gastric discomfort. One subject did not complete the study because of a vasovagal reaction that was associated with the frequent blood sampling. There was a 5–25 min lag in the appearance of measurable blood concentrations of capsaicin and phenylephrine. Most subjects had baseline caffeine concentrations from dietary use, with a gradual increase noted after 15 min consistent with GI absorption. Although the intended criterion of a 40 mmHg increase in SBP was not reached, a clinically significant increase in BP for at least 15 min was noted in the six subjects who received the highest dose of PE (30 mg), with a gradual decline over the next 2 h.

Conclusion

The ternary mixture of capsaicin, phenylephrine, and caffeine was well tolerated when administered as two sublingual/oral doses over a 2-h period.

中文翻译：

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舌下含服方治疗血管迷走性晕厥的安全性、药代动力学和药效学研究

背景

血管迷走性晕厥是晕厥的常见原因，如果反复发作，可能会产生多种负面后果，例如受伤和职业残疾。可以使用各种药物来减少血管迷走性晕厥的复发，但没有药物可以被患者用来中断感知到的血管迷走神经发作。

方法

进行了一项 I 期研究，以评估含有辣椒素 (1 mg)、盐酸去氧肾上腺素 (PE) 和柠檬酸咖啡因 (200 mg) (CPC) 的凝胶制剂在正常成年志愿者中的耐受性和安全性。次要目标是表征 CPC 制剂的药代动力学 (PK) 和实现收缩压目标增加至少 40 mmHg 所需的最高 PE 剂量。接受第一剂后，在 2 小时时给予第二剂 CPC 混合物。在 0.6、1.2 和 1.8 mg 的 PE 剂量下注意到收缩压 (SBP) 的次优变化，因此在 10、20 和 30 mg 的 PE 剂量下研究了第二个队列。以快速顺序收集血样，并对所有三种药物进行分析。

结果

共有 17 名受试者接受了该药物，没有报告严重的不良反应。尽管辣椒素含量通常会导致预期的暂时性口腔和胃部不适，但所有剂量均具有良好的耐受性。由于与频繁采血有关的血管迷走神经反应，一名受试者没有完成研究。可测量的辣椒素和去氧肾上腺素血液浓度的出现滞后 5-25 分钟。大多数受试者的基线咖啡因浓度来自饮食使用，15 分钟后逐渐增加，与胃肠道吸收一致。尽管未达到 SBP 增加 40 mmHg 的预期标准，但在接受最高剂量 PE（30 mg）的 6 名受试者中注意到 BP 在临床上显着增加至少 15 分钟，并逐渐下降。接下来 2 小时。

结论

在 2 小时内以两次舌下/口服剂量给药时，辣椒素、去氧肾上腺素和咖啡因的三元混合物耐受性良好。