Pharmacokinetics and Tolerability Evaluation of Fudosteine after Oral Administration in Healthy Korean Volunteers

건강한 한국인 자원자에서 Fudosteine 단회 경구투여에 의한 약동학적 특성 및 내약성에 관한 연구

  • Ahn, Li-Young (Department of Pharmacology and Clinical Pharmacology, Seoul National University College of Medicine and Hospital) ;
  • Shin, Kwang-Hee (Department of Pharmacology and Clinical Pharmacology, Seoul National University College of Medicine and Hospital) ;
  • Lim, Kyoung-Soo (Department of Pharmacology and Clinical Pharmacology, Seoul National University College of Medicine and Hospital) ;
  • Chung, Jae-Yong (Department of Pharmacology, Yonsei University College of Medicine) ;
  • Lee, Soon-Im (Department of Product and Business Development, Hanall Biopharma) ;
  • Yoon, Seo-Hyun (Department of Pharmacology and Clinical Pharmacology, Seoul National University College of Medicine and Hospital) ;
  • Cho, Joo-Youn (Department of Pharmacology and Clinical Pharmacology, Seoul National University College of Medicine and Hospital) ;
  • Shin, Sang-Goo (Department of Pharmacology and Clinical Pharmacology, Seoul National University College of Medicine and Hospital) ;
  • Jang, In-Jin (Department of Pharmacology and Clinical Pharmacology, Seoul National University College of Medicine and Hospital) ;
  • Yu, Kyung-Sang (Department of Pharmacology and Clinical Pharmacology, Seoul National University College of Medicine and Hospital)
  • 안리영 (서울대학교 의과대학 약리학교실 및 서울대학교병원 임상약리학과) ;
  • 신광희 (서울대학교 의과대학 약리학교실 및 서울대학교병원 임상약리학과) ;
  • 임경수 (서울대학교 의과대학 약리학교실 및 서울대학교병원 임상약리학과) ;
  • 정재용 (연세대학교 의과대학 약리학교실) ;
  • 이순임 (한올바이오파마 개발부) ;
  • 윤서현 (서울대학교 의과대학 약리학교실 및 서울대학교병원 임상약리학과) ;
  • 조주연 (서울대학교 의과대학 약리학교실 및 서울대학교병원 임상약리학과) ;
  • 신상구 (서울대학교 의과대학 약리학교실 및 서울대학교병원 임상약리학과) ;
  • 장인진 (서울대학교 의과대학 약리학교실 및 서울대학교병원 임상약리학과) ;
  • 유경상 (서울대학교 의과대학 약리학교실 및 서울대학교병원 임상약리학과)
  • Received : 2011.11.29
  • Accepted : 2011.12.27
  • Published : 2011.12.30

Abstract

Background: Fudosteine, (-)-(R)-2-amino-3-(3-hydroxypropylthio)propionic acid, is a cysteine derivative that was approved in Japan, as a new mucoactive agent. The aim of this study was to evaluate the tolerability and pharmacokinetics (PK) of fudosteine in healthy Korean subjects. Methods: A randomized, open-label, parallel, escalating single-dose study was conducted in 16 healthy Korean male subjects. The subjects were allocated to single-dose groups of 400 or 800 mg. Serial blood samples for PK analysis were collected immediately prior and after dosing up to 24 hours, and plasma concentrations were determined by high performance liquid chromatography (HPLC). Safety profiles were evaluated by monitoring adverse events and clinical evaluations throughout the study. Results: Median time to peak concentration ($T_{max}$) of both dosing group were around 0.5 hours and half-life ($t_{1/2}$) were around 3 hours. Mean peak concentration ($C_{max}$) of 400 mg and 800 mg dosing group were 10.8 and 21.5 ${\mu}g/mL$ and the mean area under the plasma concentration versus time curve from the dosing time to infinity ($AUC_{inf}$) were 26.8 and 55.0 ${\mu}g{\cdot}h/mL$, respectively. Mean dose-normalized $C_{max}$ were 0.0271 and 0.0269 ${\mu}g/mL/mg$ (P=0.923), respectively and dose-normalized $AUC_{inf}$ were 0.0669 and 0.0688 ${\mu}g{\cdot}hr/mL/mg$ (P=0.093), respectively. Fudosteine was well tolerated without any serious adverse events or clinical laboratory abnormalities. Conclusion: This study showed that fudosteine has a linear PK property and is well tolerated within 800 mg in healthy Korean volunteers.

Keywords

Acknowledgement

Supported by : 한올바이오파마(주)

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