title: Analysis of pramipexole dose-response relationships in Parkinson's disease.
abstract: BACKGROUND
  Pramipexole (PPX), a non-ergot dopamine receptor agonist, is a first-line treatment for Parkinson's disease (PD). A critical dose level above which a better benefit-to-harm ratio exists has not been examined.
  
  
  METHODS
  Chinese PD patients (n=464) were retrospectively analyzed by PPX maintenance dose, PD stage, combined levodopa dose, and baseline tremor contribution. The sum score of Baseline Activities of Daily Living (part II) and Motor Examination (III) of the Unified Parkinson's Disease Rating Scale (UPDRS II+III) was used as a covariate for final score adjustment.
  
  
  RESULTS
  Sustained-release (SR) and immediate-release (IR) PPX showed similar efficacy based on score changes at 18 weeks, with comparable tolerability. Approximately two-third of patients received PPX at ≥1.5 mg/d, and one fourth of patients had ≥20% tremor contribution to UPDRS II+III. After treatment, patients receiving PPX ≥1.5 mg/d showed better improvement in UPDRS II+III scores (P=0.0025), with similar trends with the IR and SR formulations. Patients with ≥20% tremor contribution showed better improvement in UPDRS II+III scores (P=0.0017). No differences were seen based on PD stage or combined levodopa dose. The overall proportions of adverse events (AEs) were similar. More patients discontinued because of intolerable side effects, and more investigator-defined drug-related AEs were recorded in the <1.5 mg/d subgroup.
  
  
  CONCLUSIONS
  UPDRS II+III improvement was better with PPX ≥1.5 than with <1.5 mg/d in Chinese PD patients after 18 weeks of treatment, with similar trends seen with IR and SR formulations. The frequency of AEs in PPX ≥1.5 and <1.5 mg/d subgroups was similar.
authors.affiliation: Department of Neurology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Neurology, Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology, Wuhan.
authors.forename: Sheng-Gang
authors.initials: SG
authors.lastname: Sun
authors.affiliation: Department of Neurology, Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology, Wuhan.
authors.forename: Sui-Qiang
authors.initials: SQ
authors.lastname: Zhu
authors.affiliation: Department of Neurology, The Second Affiliated Hospital of Soochow University, Suzhou.
authors.forename: Chun-Feng
authors.initials: CF
authors.lastname: Liu
authors.affiliation: Department of Neurology, Qilu Hospital Affiliated to Shandong University, Jinan.
authors.forename: Yi-Ming
authors.initials: YM
authors.lastname: Liu
authors.affiliation: Department of Neurology, Nanjing Brain Hospital, Nanjing.
authors.forename: Qing
authors.initials: Q
authors.lastname: Di
authors.affiliation: Department of Neurology, West China Hospital Affiliated to Sichuan University, Chengdu.
authors.forename: Hui-Fang
authors.initials: HF
authors.lastname: Shang
authors.affiliation: Department of Neurology, First Affiliated Hospital of China Medical University, Shenyang.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ren
authors.affiliation: Medical Department, Boehringer Ingelheim (China) Investment Co., Ltd., Shanghai, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xiang
authors.affiliation: Department of Neurology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai.
authors.forename: Sheng-Di
authors.initials: SD
authors.lastname: Chen
mesh_terms: D000978:Antiparkinson Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D052160:Benzothiazoles / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D010300:Parkinson Disease / Q000175:diagnosis / Q000188:drug therapy*; D000077487:Pramipexole; D012189:Retrospective Studies
chemical_list: D000978:Antiparkinson Agents; D052160:Benzothiazoles; D000077487:Pramipexole
keywords: Parkinson’s disease; dose dependent; pramipexole; retrospective