Clinical Pharmacology Laboratory, The Second Affiliated Hospital of Soochow University, No. 1055 Sanxiang Road, Suzhou, 215004, China.
Department of Pharmaceutics, Children's Hospital of Soochow University, No. 92 Zhongnan Street, Suzhou, 215025, China.
Clin Drug Investig. 2018 Feb;38(2):125-133. doi: 10.1007/s40261-017-0588-y.
Rasagiline tablet is an oral MAO-B inhibitor applied in early or advanced Parkinson's disease (PD). However, when patients with PD cannot take their usual oral medications, a rasagiline transdermal patch can be used as a way to offer continuous rasagiline while avoiding plasma concentration peaks and troughs. The objectives of this study were to investigate the pharmacokinetics, pharmacodynamics, and safety of the rasagiline transdermal patch in healthy Chinese subjects.
This single-dose, open-label, randomized, parallel-group study was conducted in 15 healthy subjects. Fasted subjects received a single dose of rasagiline (either by transdermal patch-1.25 mg/24 h, 1.25 mg/48 h, 2.5 mg/48 h, or 2.5 mg/72 h, or orally-in the form of a 1-mg tablet) and were monitored over a 168-h observation period to assess pharmacokinetics, pharmacodynamics, and safety.
After administration of a single-dose rasagiline transdermal patch, the mean terminal elimination half-life (t ) was 6.06-9.41 h, which was longer than with the 1-mg tablet dose (2.32 ± 0.28 h). The mean dose-normalized maximum plasma concentration (C ) of the 1-mg tablet dose was twofold higher than that of the transdermal patch groups. The mean dose-normalized areas under the concentration-time curve (AUC) of 1.25 and 2.5 mg for the rasagiline transdermal patch doses were fourfold and sevenfold higher than that of the 1-mg tablet dose, respectively. Cumulative urinary excretion was about 0.2% of the total dose. Inhibition of MAO-B activity was dose dependent, and the maximal inhibition was 73.9-94.1% at doses ranging from 1.25 to 2.5 mg. The reported adverse events were mild or moderate.
The prolonged t , increased AUC , and more stable plasma drug concentration of the rasagiline patch may permit a longer dosing interval compared to the oral tablet. The rasagiline transdermal patch was safe and well tolerated in healthy Chinese subjects.
雷沙吉兰片是一种口服单胺氧化酶-B 抑制剂，适用于早期或晚期帕金森病（PD）。然而，当 PD 患者无法服用常规口服药物时，雷沙吉兰透皮贴剂可作为一种提供持续雷沙吉兰的方式，同时避免出现血浆浓度的峰值和谷值。本研究的目的是研究健康中国受试者中单剂量雷沙吉兰透皮贴剂的药代动力学、药效学和安全性。
这是一项单次、开放标签、随机、平行组研究，共纳入 15 名健康受试者。空腹受试者接受单次雷沙吉兰给药（透皮贴剂-1.25mg/24 h、1.25mg/48 h、2.5mg/48 h 或 2.5mg/72 h，或口服-1mg 片剂），并在 168 小时观察期内进行监测，以评估药代动力学、药效学和安全性。
单次给予雷沙吉兰透皮贴剂后，平均终末消除半衰期（t ）为 6.06-9.41 h，长于 1mg 片剂剂量（2.32±0.28 h）。1mg 片剂剂量的平均剂量归一化最大血浆浓度（C ）是透皮贴剂组的两倍。雷沙吉兰透皮贴剂 1.25mg 和 2.5mg 的平均剂量归一化 AUC 分别是 1mg 片剂剂量的 4 倍和 7 倍。累积尿排泄量约为总剂量的 0.2%。MAO-B 活性抑制呈剂量依赖性，剂量范围为 1.25-2.5mg 时最大抑制率为 73.9%-94.1%。报告的不良事件为轻度或中度。
与口服片剂相比，雷沙吉兰贴剂的 t 延长、AUC 增加和更稳定的血浆药物浓度可能允许更长的给药间隔。雷沙吉兰透皮贴剂在中国健康受试者中安全且耐受良好。
