Pharmacokinetics and safety of single and multiple doses of rasagiline in healthy Japanese and caucasian subjects

Abstract

As of March 2018, rasagiline is approved for the treatment of Parkinson disease in 55 countries including Japan. The present study evaluated the pharmacokinetics (PK) and safety of rasagiline in healthy Japanese and Caucasian subjects following single and multiple administrations of three rasagiline doses. In this double-blind, placebo-controlled study, 64 healthy subjects (32 Japanese and 32 Caucasian) received either rasagiline (0.5, 1.0, or 2.0 mg) or placebo for 10 days with PK sampling for single-dose administration on day 1 and for multiple administration on day 10. Regardless of administration schedule, rasagiline plasma concentrations and dose-related increases in exposure parameters were similar between Japanese and Caucasians. Rasagiline accumulation (2-fold for 0.5 mg and 3-fold for 1.0 mg and 2.0 mg doses) following multiple administration was similar across the ethnic groups. Geometric mean ratios (GMR) comparing Japanese to Caucasians for AUC , C and AUC following single administration were 1.38, 1.17 and 1.38 for 0.5 mg; 1.22, 1.20 and 1.22 at 1.0 mg; and 1.02, 1.00 and 1.02 at for 2.0 mg. GMR for AUC and C following multiple administration were 1.43 and 1.06 at 0.5 mg, 1.06 and 1.00 at 1.0 mg, and 1.09 and 1.07 at 2.0 mg. Safety measures were unremarkable and similar between Caucasian and Japanese subjects. Comparable systemic exposure and safety parameters were demonstrated for rasagiline administered to healthy Japanese and Caucasian subjects.

Long-term, open-label, phase 3 study of rasagiline in Japanese patients with early Parkinson’s disease

“…Rasagiline is mainly metabolized by CYP1A2, which is known to exhibit no major ethnic differences. In addition, similar pharmacokinetic profiles have been reported between Japanese and Caucasian populations for rasagiline and its main metabolite (Elgardt et al 2018 ).…”

Pharmacokinetics and Bioequivalence of Rasagiline Tablets in Chinese Healthy Subjects Under Fasting and Fed Conditions: An Open, Randomized, Single-Dose, Double-Cycle, Two-Sequence, Crossover Trial

“…The difference in PK parameters obtained may have resulted from differences in subjects, sample sizes, sample detectors, or other unknown factors. Additional considerations such as interindividual variability may also contribute to this difference (Elgart et al,2019).…”

“…Rasagiline mesylate (Azilect®), developed jointly by Israel's Teva and Denmark's Lundbeck, was first approved by the European Medicines Agency (EMA) in February 2005 and then approved by the US Food and Drug Administration (FDA) in 2006 as a monotherapy in PD patients not treated with levodopa and as an adjunct therapy to levodopa in levodopatreated patients. In June 2017, rasagiline was approved by the CFDA to be listed in China and is currently used in over 50 countries by patients taking doses ranging between 0.5 mg and 1 mg daily (Finberg, 2020;Elgart et al, 2019).…”

“…According to recent surveys conducted with healthy individuals and PD patients in China and Japan, rasagiline can safely and effectively treat PD symptoms by blocking the decomposition of the neurotransmitter dopamine, with good drug tolerance and long-lasting effects (Chen et al, 2016;Elgart et al, 2019;Hattori et al, 2018;Zhang et al,2018). In general, rasagiline is a novel, safe and effective drug for the management of PD.…”

The Bioequivalence of Rasagiline Tablets in Chinese Healthy Subjects Under Fasting and Fed Conditions

“…According to recent surveys conducted with healthy individuals and PD patients in China and Japan, rasagiline can safely and effectively treat Parkinson's disease symptoms by blocking the decomposition of the neurotransmitter dopamine, with good drug tolerance and long-lasting effects [10][11][12][13] . As a whole, it is a novel , safe and effective drug to manage Parkingson's disease.…”