Xia Chen1, Qian Zhao1, Ji Jiang1, Jian Liu1, Pei Hu2. 1. Phase I Unit, Clinical Pharmacological Research Centre, Peking Union Medical College Hospital, 41# Damucang Hutong, Xicheng District, Beijing, 10032, China. 2. Phase I Unit, Clinical Pharmacological Research Centre, Peking Union Medical College Hospital, 41# Damucang Hutong, Xicheng District, Beijing, 10032, China. pei.hu.pumc@gmail.com.
Abstract
BACKGROUND AND OBJECTIVE: Although there is evidence indicating cytochome P450 (CYP) 1A2 is responsible for the metabolism of rasagiline, the role of other CYP isoforms is unclear. This study investigated the pharmacokinetics of rasagiline in adult Chinese healthy volunteers with various CYP genotypes. METHODS: This single-center, open-label study was conducted in 12 subjects. Fasted subjects received rasagiline 1 mg daily for 7 days. Blood samples were taken to determine plasma concentrations of rasagiline, its major metabolite R-1-aminoindan (AI), and the genotyping of CYP2D6 and CYP2C19. Safety was also assessed. RESULTS: After oral administration, rasagiline was absorbed with a median time to reach maximum concentration (tmax) of 0.5 h. Overall systemic exposure was approximately theefold on day 7 versus day 1. The mean terminal elimination half-life (t½) was nearly doubled on day 7 compared to day 1. AI was rapidly quantifiable in plasma with median t max occurring 1-1.5 h post-dose. Overall exposure to AI on day 7 was approximately twofold higher than on day 1. Overall systemic exposure to AI was approximately four- to sixfold greater than exposure to rasagiline, whereas maximum concentration (C max) was approximately half that of rasagiline. The mean t½ for AI was longer than for the parent drug, and was similar between the sexes and days. Inferred metabolic status did not appear to affect the pharmacokinetics of rasagiline or AI. All adverse events were mild to moderate in severity. CONCLUSION: Multiple oral administration of rasagiline 1 mg tablet in Chinese healthy adults resulted in similar pharmacokinetics of both rasagiline and AI compared to those previously observed in Caucasians. Rasagiline was safe and well tolerated in Chinese healthy volunteers.
BACKGROUND AND OBJECTIVE: Although there is evidence indicating cytochome P450 (CYP) 1A2 is responsible for the metabolism of rasagiline, the role of other CYP isoforms is unclear. This study investigated the pharmacokinetics of rasagiline in adult Chinese healthy volunteers with various CYP genotypes. METHODS: This single-center, open-label study was conducted in 12 subjects. Fasted subjects received rasagiline 1 mg daily for 7 days. Blood samples were taken to determine plasma concentrations of rasagiline, its major metabolite R-1-aminoindan (AI), and the genotyping of CYP2D6 and CYP2C19. Safety was also assessed. RESULTS: After oral administration, rasagiline was absorbed with a median time to reach maximum concentration (tmax) of 0.5 h. Overall systemic exposure was approximately theefold on day 7 versus day 1. The mean terminal elimination half-life (t½) was nearly doubled on day 7 compared to day 1. AI was rapidly quantifiable in plasma with median t max occurring 1-1.5 h post-dose. Overall exposure to AI on day 7 was approximately twofold higher than on day 1. Overall systemic exposure to AI was approximately four- to sixfold greater than exposure to rasagiline, whereas maximum concentration (C max) was approximately half that of rasagiline. The mean t½ for AI was longer than for the parent drug, and was similar between the sexes and days. Inferred metabolic status did not appear to affect the pharmacokinetics of rasagiline or AI. All adverse events were mild to moderate in severity. CONCLUSION: Multiple oral administration of rasagiline 1 mg tablet in Chinese healthy adults resulted in similar pharmacokinetics of both rasagiline and AI compared to those previously observed in Caucasians. Rasagiline was safe and well tolerated in Chinese healthy volunteers.