건강 피험자에서 lafutidine의 약동학 특성에 관한 연구

Pharmacokinetic Characteristics of Lafutidinein Healthy Subjects

  • 김보형 (서울대학교 의과대학 약리학교실 및 서울대학교병원 임상약리실) ;
  • 김정렬 (서울대학교 의과대학 약리학교실 및 서울대학교병원 임상약리실) ;
  • 임경수 (서울대학교 의과대학 약리학교실 및 서울대학교병원 임상약리실) ;
  • 김재우 (서울대학교 의과대학 약리학교실 및 서울대학교병원 임상약리실) ;
  • 김상린 (보령제약(주)) ;
  • 조주연 (서울대학교 의과대학 약리학교실 및 서울대학교병원 임상약리실) ;
  • 유경상 (서울대학교 의과대학 약리학교실 및 서울대학교병원 임상약리실) ;
  • 장인진 (서울대학교 의과대학 약리학교실 및 서울대학교병원 임상약리실) ;
  • 신상구 (서울대학교 의과대학 약리학교실 및 서울대학교병원 임상약리실)
  • Kim, Bo-Hyung (Department of Pharmacology and Clinical Pharmacology Unit, Seoul National University College of Medicine and Hospital) ;
  • Kim, Jung-Ryul (Department of Pharmacology and Clinical Pharmacology Unit, Seoul National University College of Medicine and Hospital) ;
  • Lim, Kyoung-Soo (Department of Pharmacology and Clinical Pharmacology Unit, Seoul National University College of Medicine and Hospital) ;
  • Kim, Jae-Woo (Department of Pharmacology and Clinical Pharmacology Unit, Seoul National University College of Medicine and Hospital) ;
  • Kim, Sang-Lin (Boryung Pharm. Co., Ltd.) ;
  • Cho, Joo-Youn (Department of Pharmacology and Clinical Pharmacology Unit, Seoul National University College of Medicine and Hospital) ;
  • Yu, Kyung-Sang (Department of Pharmacology and Clinical Pharmacology Unit, Seoul National University College of Medicine and Hospital) ;
  • Jang, In-Jin (Department of Pharmacology and Clinical Pharmacology Unit, Seoul National University College of Medicine and Hospital) ;
  • Shin, Sang-Goo (Department of Pharmacology and Clinical Pharmacology Unit, Seoul National University College of Medicine and Hospital)
  • 발행 : 2007.06.01

초록

Background: Lafutidine($Stogar^{(R)}$) is a novel histamine $H_2$ receptor antagonist with gastroprotective activity. It exhibited potent and long-lasting $H_2$ receptor antagonism and showed a gastroprotective effect against noxious agents-induced gastric mucosal damage through capsaicin-sensitive afferent nerves. Our objective was to determine the pharmacokinetic (PK) characteristics and safety of rising, single oral doses of lafutidine 10 mg, 20 mg, and 40 mg in healthy Korean subjects. Methods: A double-blind, dose block randomized, placebo-controlled, parallel group, single oral dose study was conducted in 30 healthy male subjects. Three groups of ten subjects received 10 mg, 20 mg, or 40 mg dosage, respectively. Two subjects in each dose group were administered matching placebo. Serial blood samples were collected for lafutidine assay during 24 h after drug administration. Pharmacokinetic parameters were determined using noncompartmental methods. Clinical safety evaluations were performed. Results: Lafutidine was rapidly absorbed with individual $T_{max}$ values ranging from 0.5 to 2 h. Mean values by dose group for oral clearance and apparent volume of distribution were similar. Lafutidine AUC and $C_{max}$ appeared to increase proportionally with dose, and dose-normalized AUC and $C_{max}$ were similar among 10 mg, 20 mg, or 40 mg dosing groups (analysis of variance, P=0.163 and 0.244, respectively). All 5 adverse events (AEs) reported were mild. No clinically significant laboratory abnormalities, vital signs or ECG measurements were observed. Conclusions: PK linearity was demonstrated up to 40 mg dosing. Lafutidine was generally safe and well tolerated with only mild AE.

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