title: Pharmacokinetic properties and tolerability of rotigotine transdermal patch after repeated-dose application in healthy korean volunteers.
abstract: OBJECTIVE
  Rotigotine, a nonergolinic dopamine receptor agonist, is a once-daily transdermal patch developed for the treatment of Parkinson's disease and restless legs syndrome. The objective of the present study was to determine the pharmacokinetic characteristics and tolerability of rotigotine transdermal patch after repeated-dose application in healthy male and female Korean subjects.
  
  
  METHODS
  In this randomized, double-blind, placebo-controlled, repeated-dose study, subjects were randomly assigned to receive either rotigotine or placebo (ratio, 20 rotigotine to 4 placebo, per sex). Rotigotine patches were applied once daily at a dose of 2 mg/24 h on days 1 to 3, followed by 4 mg/24 h on days 4 to 6. Serial blood and urine samples were collected on days 1 to 9 for the determination of the concentrations of rotigotine and its metabolites. Tolerability was evaluated by adverse events determined using physical examination, including vital signs with orthostatic measurements; ECG; and clinical laboratory testing.
  
  
  RESULTS
  A total of 48 healthy Korean subjects were enrolled (24 men, 24 women; mean age, 24 years). Approximately 50% of the total drug content was delivered within 24 hours. The mean plasma concentration of unconjugated rotigotine increased proportionally with dose. At the 2 mg/24 h dose at steady state, the geometric mean AUC0-24h and Cmax values of unconjugated rotigotine were 5.88 ng·h/mL and 0.347 ng/mL, respectively; at the 4 mg/24 h dose, the corresponding values were 13.74 ng·h/mL and 0.838 ng/mL. The mean t½ of rotigotine was 4.96 hours. At the 2 mg/24 h dose at steady state, the geometric mean AUC0-24h and Cmax values of total rotigotine were 14.02 ng·h/mL and 0.776 ng/mL; at the 4-mg/24 h dose, 32.38 ng·h/mL and 1.867 ng/mL. Common adverse events reported in the rotigotine-treated subjects included nausea (17 subjects, 42.5%), headache (11, 27.5%), and dizziness (9, 22.5%). No clinically significant changes in blood pressure, ECG, or laboratory values were observed.
  
  
  CONCLUSIONS
  The mean plasma exposures of unconjugated rotigotine increased proportionally with dose. Repeated daily application of the rotigotine patch was well tolerated in these healthy Korean volunteers. ClinicalTrials.gov identifier: NCT01964573.
authors: Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea; Department of Clinical Pharmacology and Therapeutics, Kyung Hee University College of Medicine and Hospital, Seoul, Republic of Korea.
authors: Bo-Hyung
authors: BH
authors: Kim
authors: Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea. Electronic address: ksyu@snu.ac.kr.
authors: Kyung-Sang
authors: KS
authors: Yu
authors: Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea.
authors: In-Jin
authors: IJ
authors: Jang
authors: Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea; Department of Clinical Pharmacology and Therapeutics, CHA University School of Medicine and CHA Bundang Medical Center, Seongnam, Republic of Korea.
authors: Kyoung
authors: K
authors: Soo Lim
authors: Department of Clinical Pharmacology and Therapeutics, Samsung Medical Center, Seoul, Republic of Korea.
authors: Jung-Ryul
authors: JR
authors: Kim
authors: UCB Pharma, Monheim and Rhein, Germany.
authors: Jan-Peer
authors: JP
authors: Elshoff
authors: UCB Pharma, Monheim and Rhein, Germany.
authors: Jens-Otto
authors: JO
authors: Andreas
authors: UCB Pharma, Monheim and Rhein, Germany.
authors: Marina
authors: M
authors: Braun
authors: UCB Pharma, Monheim and Rhein, Germany.
authors: Willi
authors: W
authors: Cawello
mesh_terms: D000328:Adult; D044466:Asian People; D018491:Dopamine Agonists / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004311:Double-Blind Method; D005260:Female; D006261:Headache / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage* / Q000493:pharmacokinetics; D013876:Thiophenes / Q000008:administration & dosage* / Q000493:pharmacokinetics; D057968:Transdermal Patch; D055815:Young Adult
chemical_list: D018491:Dopamine Agonists; D013764:Tetrahydronaphthalenes; D013876:Thiophenes; C047508:rotigotine
keywords: pharmacokinetics; rotigotine; safety; tolerability