title: Pharmacokinetics of Rasagiline in Healthy Adult Chinese Volunteers with Various Genotypes: A Single-Center, Open-Label, Multiple-Dose Study.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Phase I Unit, Clinical Pharmacological Research Centre, Peking Union Medical College Hospital, 41# Damucang Hutong, Xicheng District, Beijing, 10032, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Chen
authors.affiliation: Phase I Unit, Clinical Pharmacological Research Centre, Peking Union Medical College Hospital, 41# Damucang Hutong, Xicheng District, Beijing, 10032, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Phase I Unit, Clinical Pharmacological Research Centre, Peking Union Medical College Hospital, 41# Damucang Hutong, Xicheng District, Beijing, 10032, China.
authors.forename: Ji
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Phase I Unit, Clinical Pharmacological Research Centre, Peking Union Medical College Hospital, 41# Damucang Hutong, Xicheng District, Beijing, 10032, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Pei
authors.initials: P
authors.lastname: Hu
mesh_terms: D000284:Administration, Oral; D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D044466:Asian People / Q000235:genetics*; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005215:Fasting / Q000378:metabolism; D005260:Female; D005838:Genotype; D064368:Healthy Volunteers; D006801:Humans; D007189:Indans / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D008297:Male; D055815:Young Adult
chemical_list: D007189:Indans; C031967:rasagiline; D001189:Aryl Hydrocarbon Hydroxylases; D019389:Cytochrome P-450 CYP2D6; C105144:cytochrome P-450 CYP2D19 (marmoset)