Bioequivalence Evaluation of Two Brands of Zolpidem Tartrate 10 mgTablets (Zanilo and Stilnox) in Healthy Male Volunteers

Bioequivalence Evaluation of Two Brands of Zolpidem Tartrate 10 mgTablets (Zanilo and Stilnox) in Healthy Male Volunteers

The purpose of the present study was to evaluate the bioequivalence of two zolpidem tartrate tablets, Stilnox tablet (Sanofi-aventis Korea, reference product) and Zanilo tablet (ChoDang Pharm Co., Ltd., Korea, test product), according to the guidelines of Korea Food and Drug Administration (KFDA). After adding an internal standard (cimetropium), 250 L plasma samples were extracted using 1.3 mL of ethyl acetate. Extracted compounds were analyzed by HPLC with triple-quadrupole mass spectrometry. This method for determination of zolpidem is proved accurate and reproducible with the limit of quantitation of 1 ng/mL in human plasma. Twenty-four healthy male Korean volunteers received each medicine at the zolpidem tartrate dose of 10 mg in a 2 ´ 2 crossover study. There was one-week washout period between the doses. Plasma concentrations of zolpidem were monitored for over a period of 8 hr after the administration. AUC0-t (the area under the plasma concentration-time curve) was calculated by the linear trapezoidal rule. Cmax (maximum plasma drug concentration) and Tmax (time to reach Cmax) were compiled from the plasma concentration-time data. Analysis of variance was carried out using logarithmically transformed AUC0-t 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 for the log transformed data were acceptable range of log 0.8 to log 1.25 (e.g., log 0.92-log 1.06 for AUC0-t, log 0.96-log 1.13 for Cmax). The major parameters, AUC0-t and Cmax, met the criteria of KFDA for bioequivalence indicating that Zanilo tablet is bioequivalent to Stilnox tablet.

The purpose of the present study was to evaluate the bioequivalence of two zolpidem tartrate tablets, Stilnox tablet (Sanofi-aventis Korea, reference product) and Zanilo tablet (ChoDang Pharm Co., Ltd., Korea, test product), according to the guidelines of Korea Food and Drug Administration (KFDA). After adding an internal standard (cimetropium), 250 L plasma samples were extracted using 1.3 mL of ethyl acetate. Extracted compounds were analyzed by HPLC with triple-quadrupole mass spectrometry. This method for determination of zolpidem is proved accurate and reproducible with the limit of quantitation of 1 ng/mL in human plasma. Twenty-four healthy male Korean volunteers received each medicine at the zolpidem tartrate dose of 10 mg in a 2 ´ 2 crossover study. There was one-week washout period between the doses. Plasma concentrations of zolpidem were monitored for over a period of 8 hr after the administration. AUC0-t (the area under the plasma concentration-time curve) was calculated by the linear trapezoidal rule. Cmax (maximum plasma drug concentration) and Tmax (time to reach Cmax) were compiled from the plasma concentration-time data. Analysis of variance was carried out using logarithmically transformed AUC0-t 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 for the log transformed data were acceptable range of log 0.8 to log 1.25 (e.g., log 0.92-log 1.06 for AUC0-t, log 0.96-log 1.13 for Cmax). The major parameters, AUC0-t and Cmax, met the criteria of KFDA for bioequivalence indicating that Zanilo tablet is bioequivalent to Stilnox tablet.