Consultant for Japan Clinical Pharmacology Laboratories, Ltd, Tokyo, Japan.
Clin Drug Investig. 2005;25(3):199-208. doi: 10.2165/00044011-200525030-00006.
Oral zolmitriptan is highly effective in the acute treatment of migraine. However, nausea and vomiting during attacks may limit the usefulness of oral medications. An alternative, nasal spray, formulation has been developed that demonstrates good efficacy, high tolerability and a very fast onset of action. This study assessed the pharmacokinetics and bioavailability of zolmitriptan and its active metabolite 183C91 in healthy Japanese subjects following single-dose (2.5 or 5mg) oral or intranasal administration.
This was a single-centre, open-label, randomised, crossover study. Forty-eight subjects each received one oral and one intranasal dose of 2.5 or 5mg zolmitriptan, with a 72-hour washout period between doses. Blood was drawn at various timepoints from 2 minutes to 15 hours post-dose and urine was collected over the course of the study; samples were analysed for zolmitriptan and 183C91, from which pharmacokinetic parameters were calculated.
Zolmitriptan was detected in plasma 2 minutes after intranasal administration in the majority of subjects (~75%) compared with 10 minutes after oral administration. The intranasal : tablet ratio for zolmitriptan area under the concentration-time curve from time zero to infinity was 0.924 (90% CI 0.826, 1.033) and 0.960 (90% CI 0.865, 1.066) for the 2.5 and 5mg doses, respectively. Other pharmacokinetic parameters were similar between the two formulations. While 183C91 appeared in the plasma concurrently to zolmitriptan after oral dosing, its appearance was delayed to approximately 30 minutes after intranasal dosing. Zolmitriptan was safe and well tolerated at both doses.
The rapid absorption of zolmitriptan nasal spray may explain the faster relief from migraine reported in patients compared with oral zolmitriptan.
口腔给予佐米曲普坦在偏头痛的急性治疗中具有高度疗效。然而，发作期间的恶心和呕吐可能限制了口服药物的使用。已经开发出一种替代的鼻腔喷雾剂配方，该配方显示出良好的疗效、高耐受性和非常快速的作用开始。本研究评估了佐米曲普坦及其活性代谢物 183C91 在健康日本受试者中单剂量（2.5 或 5mg）口服或鼻内给药后的药代动力学和生物利用度。
这是一项单中心、开放标签、随机、交叉研究。48 名受试者每人分别接受一次口服和一次鼻内给予 2.5 或 5mg 佐米曲普坦，两次剂量之间有 72 小时的洗脱期。在给药后 2 分钟至 15 小时从各个时间点抽取血液，并在研究过程中收集尿液；对样品进行分析以检测佐米曲普坦和 183C91，从这些样品中计算药代动力学参数。
在大多数受试者中（约 75%），与口服给药后 10 分钟相比，鼻腔给药后 2 分钟即可检测到佐米曲普坦在血浆中。从零时间到无穷大的佐米曲普坦浓度-时间曲线下面积的鼻腔：片剂比值分别为 0.924（90%CI 0.826，1.033）和 0.960（90%CI 0.865，1.066），分别用于 2.5mg 和 5mg 剂量。两种制剂的其他药代动力学参数相似。虽然在口服给药后 183C91 与佐米曲普坦同时出现在血浆中，但它的出现延迟至鼻内给药后约 30 分钟。两种剂量下，佐米曲普坦均安全且耐受良好。
佐米曲普坦鼻腔喷雾剂的快速吸收可能解释了与口服佐米曲普坦相比，患者报告的偏头痛缓解更快。
