리피토정R (아토르바스타틴 20m g)에 대한 아토르바정R의 생물학적동등성 (Bioequivalence of Atorva TabletR to Lipitor TabletR (Atorvastatin 20mg))

서지정보

· 발행기관 : 한국약제학회
· 수록지 정보 : Journal of Pharmaceutical Investigation / 38권 / 2호 / 135 ~ 142페이지
· 저자명 : 임현균, 송진호, 이태호, 염정록, 이재현, 한상범

초록

The present study describes the evaluation of the bioequivalence of two atorvastatin tablets, Lipitor TabletR (Pfizer, reference drug) and Atorva TabletR (Yuhan, test drug), according to the guidelines of Korea Food and Drug Administration (KFDA). Forty-nine healthy male Korean volunteers received each medicine at the atorvastatin dose of 40 mg in a 2 ´ 2 crossover study with a two weeks washout interval. After drug administration, serial blood samples were collected at a specific time interval from 0 - 48 hours. The plasma atorvastatin concentrations were monitored by an high performance liquid chromatography -tandem mass spectrometer (LC-MS/MS) employing electrospray ionization technique and operating in multiple reaction monitoring (MRM) and positive ion mode. The total chromatographic run time was 4.5 min and calibration curves were linear over the concentration range of 0.1-100 ng/mL for atorvastatin. The method was validated for selectivity, sensitivity, linearity, accuracy and precision. AUCt (the area under the plasma concentration-time curve from time zero to 48 hr) was calculated by the linear log trapezoidal rule method. Cmax (maximum plasma drug concentration) and Tmax (time to reach Cmax) were complied from the plasma concentration-time data. Analysis of variance was carried out using logarithmically transformed AUCt and Cmax. No significant sequence effect was found for all of the bioavailability parameters indicating that the crossover design was properly performed. The 90% confidence intervals of the AUCt ratio and the Cmax ratio for Atorva TabletR / Lipitor TabletR were log 0.9413 ~ log 1.0179 and log 0.8318 ~ log 1.0569, respectively. These values were within the acceptable bioequivalence intervals of log 0.8 ~ log 1.25. Based on these statistical considerations, it was concluded that the test drug, Atorva TabletR was bioequivalent to the reference drug, Lipitor Tablet.

영어초록

The present study describes the evaluation of the bioequivalence of two atorvastatin tablets, Lipitor TabletR (Pfizer, reference drug) and Atorva TabletR (Yuhan, test drug), according to the guidelines of Korea Food and Drug Administration (KFDA). Forty-nine healthy male Korean volunteers received each medicine at the atorvastatin dose of 40 mg in a 2 ´ 2 crossover study with a two weeks washout interval. After drug administration, serial blood samples were collected at a specific time interval from 0 - 48 hours. The plasma atorvastatin concentrations were monitored by an high performance liquid chromatography -tandem mass spectrometer (LC-MS/MS) employing electrospray ionization technique and operating in multiple reaction monitoring (MRM) and positive ion mode. The total chromatographic run time was 4.5 min and calibration curves were linear over the concentration range of 0.1-100 ng/mL for atorvastatin. The method was validated for selectivity, sensitivity, linearity, accuracy and precision. AUCt (the area under the plasma concentration-time curve from time zero to 48 hr) was calculated by the linear log trapezoidal rule method. Cmax (maximum plasma drug concentration) and Tmax (time to reach Cmax) were complied from the plasma concentration-time data. Analysis of variance was carried out using logarithmically transformed AUCt and Cmax. No significant sequence effect was found for all of the bioavailability parameters indicating that the crossover design was properly performed. The 90% confidence intervals of the AUCt ratio and the Cmax ratio for Atorva TabletR / Lipitor TabletR were log 0.9413 ~ log 1.0179 and log 0.8318 ~ log 1.0569, respectively. These values were within the acceptable bioequivalence intervals of log 0.8 ~ log 1.25. Based on these statistical considerations, it was concluded that the test drug, Atorva TabletR was bioequivalent to the reference drug, Lipitor Tablet.

참고자료

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