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The prediction of plasma and brain levels of 2,3,5,6-tetramethylpyrazine following transdermal application

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Abstract

The purpose of this study was to construct a pharmacokinetic (PK) model and to determine PK parameters of 2,3,5,6-tetramethylpyrazine (TMP) after application of TMP transdermal delivery system. Data were obtained in Sprague-Dawley (SD) rats following a single dose of TMP transdermal delivery system. Blood samples were obtained at 0, 0.25, 0.5, 1, 2, 4, 6, 16, and 24 hours after the transdermal application. In the brain level study, 18 SD rats were divided into 6 groups. Three SD rats before and after transdermal application were culled and sacrificed at each of the following time intervals: 2, 4, 6, 16, and 24 hours after the TMP-TTS application. TMP concentrations in plasma and brain tissues were determined using high performance liquid chromatography and data were fitted using a zero-order absorption and a firstorder-elimination 3-compartment PK model. Fitted parameters included 2 volumes of distribution (V1, V2) and 2 elimination rate constants (k10, k20). The elimination half-life for TMP in plasma and brain was 26.5 and 31.2 minutes, respectively. The proposed PK model fit observed concentrations of TMP very well. This model is useful for predicting drug concentrations in plasma and brain and for assisting in the development of transdermal systems.

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Author notes

  1. Xiaohong Qi

    Present address: Global Product Development, Bristol-Myers Squibb, Worldwide Consumer Medicines, 1350 Liberty Avenue, 07111, Hillside, NJ

Authors and Affiliations

  1. Global Product Development, Bristol-Myers Squibb, Worldwide Consumer Medicines, 1350 Liberty Avenue, 07111, Hillside, NJ

    Rong (Ron) Liu

  2. School of Pharmacy, University of Michigan, 428 Church Street, Ann Arbor, MI, 48109-1065

    Chrisita Ackermann

  3. Pharmaceutical Research Institute, Bristol-Myers Squibb, 08903, New Brunswick, NJ

    Duxin Sun

  4. Medical Radiology Research Institute, School of Medicine, Fudan University, Yixueyuan Road, 200032, Shanghai, People's Republic of China

    Minli Sheng

  5. Shanghai Institute of Industrial Pharmaceutics, National Pharmaceutical Engineering Research Center, Zhongshanbeiyi Road, No. 1111, 200437, Shanghai, People's Republic of China

    Huimin Hou

Authors
  1. Xiaohong Qi
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  2. Chrisita Ackermann
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  3. Duxin Sun
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  4. Rong (Ron) Liu
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  5. Minli Sheng
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Published: December 13, 2002

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Qi, X., Ackermann, C., Sun, D. et al. The prediction of plasma and brain levels of 2,3,5,6-tetramethylpyrazine following transdermal application. AAPS J 4, 46 (2002). https://doi.org/10.1208/ps040446

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  • DOI: https://doi.org/10.1208/ps040446

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