Journal of Korean Society for Clinical Pharmacology and Therapeutics (임상약리학회지)

Korean Society for Clinical Pharmacology and Therapeutics (대한임상약리학회)
권호 표지

A Randomized, Placebo Controlled, Double Blind, Parallel Group, Multiple Dosing, Dose Escalation Clinical Study to Evaluate Pharmacokinetics/Pharmacodynamics and Tolerability of Zofenopril in Healthy Korean Subjects

건강한 한국인에서 Zofenopril의 약동/약력학적 특성 및 내약성에 관한 무작위, 위약대조, 이중맹검, 평행군, 반복투여, 단계적 증량 임상연구

  • Oh, Jaeseong (Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital) ;
  • Lee, SeungHwan (Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital) ;
  • Lim, Kyoung Soo (Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital) ;
  • Chung, Jae-Yong (Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital) ;
  • Shin, Sang-Goo (Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital) ;
  • Jang, In-Jin (Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital) ;
  • Yu, Kyung-Sang (Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital)
  • 오재성 (서울대학교 의과대학 임상약리학교실 및 서울대학교병원 임상약리학과) ;
  • 이승환 (서울대학교 의과대학 임상약리학교실 및 서울대학교병원 임상약리학과) ;
  • 임경수 (서울대학교 의과대학 임상약리학교실 및 서울대학교병원 임상약리학과) ;
  • 정재용 (서울대학교 의과대학 임상약리학교실 및 서울대학교병원 임상약리학과) ;
  • 신상구 (서울대학교 의과대학 임상약리학교실 및 서울대학교병원 임상약리학과) ;
  • 장인진 (서울대학교 의과대학 임상약리학교실 및 서울대학교병원 임상약리학과) ;
  • 유경상 (서울대학교 의과대학 임상약리학교실 및 서울대학교병원 임상약리학과)
  • Received : 2013.06.19
  • Accepted : 2013.06.27
  • Published : 2013.06.30
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Abstract

Background: Zofenopril is a new Angiotensin Converting Enzyme (ACE) inhibitor for the treatment of the patients with hypertension and congestive heart failure. This study aimed to evaluate the pharmacokinetics (PKs)/pharmacodynamics (PDs) and tolerability of zofenopril in healthy Korean subjects. Methods: A randomized, double blind, placebo-controlled, multiple dosing parallel group study with two dosage groups (zofenopril 30 mg or 60 mg) was conducted in healthy Korean male subjects. Each dosage group consisted of 10 subjects and they were randomly assigned to receive zofenopril or placebo with a ratio of 4:1. PK characteristics of zofenopril and its active metabolite, zofenoprilat, were evaluated after single or multiple dosing. Serum ACE activities and blood pressures were measured for PD evaluation. Adverse events, clinical laboratory tests, electrocardiograms, vital signs and physical examinations were performed for tolerability evaluation. Results: The PK characteristics of zofenopril and zofenoprilat after single dose and multiple doses were similar to one another. The metabolic ratio of zofenoprilat to zofenopril after single dose and multiple doses were 12.4 and 14.9, respectively, in the 30 mg dosage group, and were 6.8 and 6.6, respectively, in the 60 mg dosage group. Complete serum ACE activity inhibition was observed within 1 hour in both doses but it was maintained longer in the 60 mg dosage group compared to the 30 mg dosage group. There were no clinically significant abnormalities in tolerability evaluations. Conclusion: The PK/PD characteristics of zofenopril and zofenoprilat after single or multiple administrations were explored. Zofenopril was well tolerated after multiple administrations in healthy Korean subjects.

Keywords

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