Journal of Pharmaceutical Investigation

The Korean Society of Pharmaceutical Sciences and Technology (한국약제학회)
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Bioequivalence of Losata Tablet to Cozaar Tablet (Losartan Potassium 50 mg) using HPLC with Fluorescence Detector

고속액체크로마토그래피-형광검출기를 이용한 코자 정(로자탄칼륨 50 mg)에 대한 로사타 정의 생물학적동등성

  • Kang, Hyun-Ah (Pharmaceutical Research Institute, CJ Cheiljedang Corp.) ;
  • Kim, Se-Mi (Research Institute, ChongKunDang Pharm.) ;
  • Yoo, Dong-Jin (Institute of Bioequivalence and Bridging Study, College of Pharmacy, Chonnam National University) ;
  • Kang, Seung-Rae (Institute of Bioequivalence and Bridging Study, College of Pharmacy, Chonnam National University) ;
  • Lee, Sang-No (Institute of Bioequivalence and Bridging Study, College of Pharmacy, Chonnam National University) ;
  • Kim, Yong-Hee (Institute of Bioequivalence and Bridging Study, College of Pharmacy, Chonnam National University) ;
  • Lee, Yong-Bok (Institute of Bioequivalence and Bridging Study, College of Pharmacy, Chonnam National University)
  • 강현아 (CJ 제일제당 제약연구소) ;
  • 김세미 (종근당 종합연구소) ;
  • 유동진 (전남대학교 약학대학 부속 생물학적동등성 및 가교시험연구소) ;
  • 강승래 (전남대학교 약학대학 부속 생물학적동등성 및 가교시험연구소) ;
  • 이상노 (전남대학교 약학대학 부속 생물학적동등성 및 가교시험연구소) ;
  • 김용희 (전남대학교 약학대학 부속 생물학적동등성 및 가교시험연구소) ;
  • 이용복 (전남대학교 약학대학 부속 생물학적동등성 및 가교시험연구소)
  • Published : 2010.02.20
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Abstract

Losartan potassium, 2-butyl-4-chloro-1-[p-(o-1H-tetrazol-5-ylphenyl)benzyl]imidazole-5-methanol mono-potassium salt, is a new class of antihypertensive agents, and is an antagonist in angiotensin receptor. The purpose of the present study was to evaluate the bioequivalence of two Losartan potassium tablets, Cozaar tablet (MSD Pharmaceutical Co., Ltd.) and Losata tablet (Kyung Dong Pharmaceutical Co., Ltd.), according to the guidelines of the Korea Food and Drug Administration (KFDA). The release of losartan from the two losartan potassium formulations in vitro was tested using KP VIII Apparatus II method with various dissolution media. Twenty eight healthy male subjects, $23.86{\pm}1.80$ years in age and $67.27{\pm}6.60\;kg$ in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After a single tablet containing 50 mg as losartan potassium was orally administered, blood samples were taken at predetermined time intervals, and the concentrations of losartan in serum were determined using HPLC with fluorescence detector. The dissolution profiles of two formulations were similar in all tested dissolution media. The pharmacokinetic parameters such as $AUC_t$, $C_{max}$ and $T_{max}$ were calculated, and Equiv Test/K-BE Test 2002 was utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_t$, $C_{max}$ and untransformed $T_{max}$. The results showed that the differences between two formulations based on the reference drug, Cozaar, were -2.70%, 1.45% and 2.31% for $AUC_t$, $C_{max}$ and $T_{max}$, respectively. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log 0.8 to log 1.25 (e.g., log 0.8852~log 1.0655 and log 0.8319~log 1.2342 for $AUC_t$ and $C_{max}$, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating Losata tablet was bioequivalent to Cozaar tablet.

Keywords

References

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