Pharmacokinetics, Pharmacodynamics, and Safety of Rasagiline Transdermal Patch: A Preliminary Study in Healthy Chinese Subjects.

Background And Objectives: 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.

Methods: 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.

Results: 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.

Conclusion: 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.