AAPS PharmSci

, Volume 4, Issue 4, pp 243–250 | Cite as

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

  • Xiaohong Qi
  • Chrisita Ackermann
  • Duxin Sun
  • Rong (Ron) Liu
  • Minli Sheng
  • Huimin Hou


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.


tetramethylpyrazine percutaneous absorption transdermal drug delivery system in vitro/in vivo pharmacokinetic model 


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Copyright information

© American Association of Pharmaceutical Scientists 2002

Authors and Affiliations

  • Xiaohong Qi
    • 1
  • Chrisita Ackermann
    • 2
  • Duxin Sun
    • 3
  • Rong (Ron) Liu
    • 1
  • Minli Sheng
    • 4
  • Huimin Hou
    • 5
  1. 1.Global Product Development, Bristol-Myers SquibbWorldwide Consumer MedicinesHillside
  2. 2.School of PharmacyUniversity of MichiganAnn Arbor
  3. 3.Pharmaceutical Research InstituteBristol-Myers SquibbNew Brunswick
  4. 4.Medical Radiology Research Institute, School of MedicineFudan UniversityShanghaiPeople's Republic of China
  5. 5.Shanghai Institute of Industrial PharmaceuticsNational Pharmaceutical Engineering Research CenterShanghaiPeople's Republic of China

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