title: Pharmacokinetics, safety, and tolerability of rotigotine transdermal system in healthy Japanese and Caucasian subjects following multiple-dose administration.
abstract: Rotigotine is a dopamine receptor agonist indicated for the treatment of Parkinson's disease and moderate-to-severe restless legs syndrome. Continuous transdermal delivery of rotigotine via a silicon-based patch maintains stable plasma concentrations over 24 h. The objective of the study was to evaluate the pharmacokinetics, safety, and tolerability of a multiple-dose schedule of rotigotine transdermal patch in Japanese and Caucasian subjects. In this open-label, repeated-dose, parallel-group study (ClinicalTrials.gov: NCT01854216), healthy male and female subjects of Japanese or Caucasian ethnic origin were matched by gender, body mass index, and age. Subjects underwent a 9-day patch application period. 12 Japanese and 12 Caucasian subjects were included in the pharmacokinetic analyses. Mean apparent doses (actual amount of drug delivered) increased proportionally with rotigotine nominal dosages (1, 2, and 4 mg/24 h) and were similar for both ethnic groups, with large inter-individual variability. Mean plasma concentration-time profiles for unconjugated rotigotine were similar in both ethnic groups at day 3 for each dosage. Peak concentrations (C max,ss) and area under the concentration-time curves from pre-dose to the concentration measured 24 h after administration of patch (AUC(0-24,ss)) showed similar exposure in both groups; higher values in Japanese subjects were explained by differences in body weight. For total rotigotine, C max,ss and AUC(0-24,ss) values were higher in Caucasian subjects and could be explained by small differences in apparent dose. Rotigotine was generally well tolerated following multiple applications up to 4 mg/24 h. These findings suggest similar dosage requirements for rotigotine transdermal system in Japanese and Caucasian populations.
authors.affiliation: UCB Pharma, Alfred-Nobel-Str. 10, 40789, Monheim am Rhein, Germany. Willi.Cawello@ucb.com.
authors.forename: Willi
authors.initials: W
authors.lastname: Cawello
authors.affiliation: Otsuka Pharmaceutical Co., Ltd., Tokyo, Japan.
authors.forename: Seong Ryul
authors.initials: SR
authors.lastname: Kim
authors.affiliation: UCB Pharma, Alfred-Nobel-Str. 10, 40789, Monheim am Rhein, Germany.
authors.forename: Marina
authors.initials: M
authors.lastname: Braun
authors.affiliation: UCB Pharma, Alfred-Nobel-Str. 10, 40789, Monheim am Rhein, Germany.
authors.forename: Jan-Peer
authors.initials: JP
authors.lastname: Elshoff
authors.affiliation: Kitassato University, Tokyo, Japan.
authors.forename: Takeuchi
authors.initials: T
authors.lastname: Masahiro
authors.affiliation: Otsuka Pharmaceutical Co., Ltd., Tokyo, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Ikeda
authors.affiliation: Otsuka Pharmaceutical Co., Ltd., Tokyo, Japan.
authors.forename: Tomoo
authors.initials: T
authors.lastname: Funaki
mesh_terms: D000279:Administration, Cutaneous; D000328:Adult; D019540:Area Under Curve; D044466:Asian People; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D013876:Thiophenes / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D057968:Transdermal Patch / Q000009:adverse effects*; D044465:White People; D055815:Young Adult
chemical_list: D018491:Dopamine Agonists; D013764:Tetrahydronaphthalenes; D013876:Thiophenes; C047508:rotigotine
keywords: Dopamine agonist; Ethnic groups; Japanese/Caucasian comparison; Multiple doses; Pharmacokinetics; Rotigotine; Transdermal delivery