Shadle C R, Liu G, Goldberg M R
Merck Research Laboratories, West Point, Pennsylvania, USA.
J Clin Pharmacol. 2000 Mar;40(3):309-15. doi: 10.1177/00912700022008865.
Rizatriptan (MAXALT), a potent, oral 5-HT1B/1D agonist with a rapid onset of action, is available now for the acute treatment of migraine. This study examined the pharmacokinetic and clinical interaction between rizatriptan 10 mg and the components (ethinyl estradiol [EE] 35 micrograms and norethindrone [NET] 1.0 mg) of a well-established oral contraceptive combination product, ORTHO-NOVUM 1/35. Levels of sex hormone binding globulin (SHBG), a protein increased by EE to which NET binds, were also examined. In this two-period crossover study, 20 healthy young female subjects received a coadministration of 8 days of rizatriptan treatment (6 days of single-dose 10 mg rizatriptan and 2 days of multiple-dose rizatriptan, 10 mg q 4 hours for three doses, giving a total daily dose of 30 mg on Days 7 and 8) or matching placebo along with their daily dose (one tablet) of ORTHO-NOVUM 1/35 within their oral contraceptive cycle. Plasma was sampled for EE, NET, and SHBG concentrations. Safety evaluations included routine laboratory safety studies, physical examinations, and monitoring for ECG, vital signs, and adverse events. There were no statistically significant differences in any of the pharmacokinetic parameters of EE or NET between the rizatriptan and placebo treatment periods, thus indicating that rizatriptan had no meaningful effect on the disposition of either the EE or the NET component of ORTHO-NOVUM 1/35. The SHBG concentration did not change throughout the entire study. Clinically, coadministration of rizatriptan with ORTHO-NOVUM 1/35 was well tolerated. Blood pressure, heart rate, and temperature showed no consistent trend or clinically important changes. Adverse events following coadministration of rizatriptan with ORTHO-NOVUM 1/35 were similar to those reported when placebo was given with ORTHO-NOVUM 1/35. The findings of this study indicate that there is little potential for dosages as high as 30 mg/day, the maximum recommended dosing schedule, of rizatriptan to alter the plasma concentrations of oral contraceptives.
利扎曲普坦（麦克斯林）是一种起效迅速的强效口服5-羟色胺1B/1D激动剂，目前可用于偏头痛的急性治疗。本研究检测了10毫克利扎曲普坦与一种成熟的口服避孕药复方制剂（炔雌醇[EE]35微克和炔诺酮[NET]1.0毫克）的成分——复方口服避孕药1/35之间的药代动力学及临床相互作用。同时还检测了性激素结合球蛋白（SHBG）的水平，SHBG是一种因EE升高而使NET与之结合的蛋白质。在这项两阶段交叉研究中，20名健康年轻女性受试者在其口服避孕药周期内，接受为期8天的利扎曲普坦治疗（6天单剂量10毫克利扎曲普坦和2天多剂量利扎曲普坦，每4小时10毫克，共三剂，第7天和第8天的日总剂量为30毫克）或匹配的安慰剂与她们每天剂量（一片）的复方口服避孕药1/35同时服用。采集血浆检测EE、NET和SHBG浓度。安全性评估包括常规实验室安全性研究、体格检查以及对心电图、生命体征和不良事件的监测。利扎曲普坦治疗期与安慰剂治疗期之间，EE或NET的任何药代动力学参数均无统计学显著差异，这表明利扎曲普坦对复方口服避孕药1/35的EE或NET成分的处置没有显著影响。整个研究过程中SHBG浓度未发生变化。临床上，利扎曲普坦与复方口服避孕药1/35同时服用耐受性良好。血压、心率和体温未显示出一致的趋势或具有临床意义的变化。利扎曲普坦与复方口服避孕药1/35同时服用后的不良事件与安慰剂和复方口服避孕药1/35同时服用时报告的不良事件相似。本研究结果表明，对于利扎曲普坦高达30毫克/天（最大推荐给药方案）的剂量，几乎没有改变口服避孕药血浆浓度的可能性。
