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Pharmacokinetic and Bioequivalence Study of Zolpidem Tartate in Healthy Volunteers

  • Park, Jun-Sung (Center for Nanotechnology-based New Drug Dosage Form, College of Pharmacy, Chungnam National University) ;
  • Myung, Ja-Hye (Center for Nanotechnology-based New Drug Dosage Form, College of Pharmacy, Chungnam National University) ;
  • Wang, Hun-Sik (Center for Nanotechnology-based New Drug Dosage Form, College of Pharmacy, Chungnam National University) ;
  • Koo, Ja-Seong (Center for Nanotechnology-based New Drug Dosage Form, College of Pharmacy, Chungnam National University) ;
  • Cho, Won-Kyung (Center for Nanotechnology-based New Drug Dosage Form, College of Pharmacy, Chungnam National University) ;
  • Cha, Kwang-Ho (Center for Nanotechnology-based New Drug Dosage Form, College of Pharmacy, Chungnam National University) ;
  • Park, Hee-Jun (Center for Nanotechnology-based New Drug Dosage Form, College of Pharmacy, Chungnam National University) ;
  • Kim, Min-So (Center for Nanotechnology-based New Drug Dosage Form, College of Pharmacy, Chungnam National University) ;
  • Kim, Jeong-Soo (Center for Nanotechnology-based New Drug Dosage Form, College of Pharmacy, Chungnam National University) ;
  • Hwang, Sung-Joo (Center for Nanotechnology-based New Drug Dosage Form, College of Pharmacy, Chungnam National University)
  • Received : 2011.03.24
  • Accepted : 2011.05.27
  • Published : 2011.06.20

Abstract

In this study simple and sensitive high performance liquid chromatographic method using a commercially available column, was developed and validated for the determination of zolpidem tartrate in human plasma. The developed method with suitable validation was applied to a bioequivalence study of two different kinds of zolpidem tartrate. Two different formulations containing 10 mg of zolpidem tartate (CAS : 99294-93-6) were compared in 24 healthy male volunteers in order to compare the bioavailability and prove the bioequivalence. The study was performed in an open, single dose randomized, 2-sequence, cross-over design in 24 healthy male volunteers with a one-week washout period. Blood samples for pharmacokinetic profiling were drawn at selected times during 12 h. The mean $AUC_{0-12h}$, $C_{max}$, $T_{max}$ and $T_{1/2}$ were $676.6{\pm}223.4$ $ng{\cdot}h{\cdot}mL^{-1}$, $177.4{\pm}34.2$ $ng{\cdot}mL^{-1}$, and $0.8{\pm}0.4$ and $3.5{\pm}2.1$, respectively, for the test formulations, and $640.7{\pm}186.6$ $ng{\cdot}h{\cdot}mL^{-1}$, $193.0{\pm}64.5$ $ng{\cdot}mL^{-1}$, and $0.9{\pm}0.4$ and $2.7{\pm}0.9$, respectively, for the reference formulation. Both primary target parameters $AUC_{0-12h}$ and $C_{max}$ were log-transformed and tested parametrically by analysis of variance (ANOVA). 90% confidence intervals of $AUC_{0-12h}$ and $C_{max}$ were in the range of acceptable limits of bioequivalence (80-125%). Based on these results, the two formulations of zolpidem tartate are considered to be bioequivalent.

Keywords

References

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