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The Prediction of Plasma and Brain Levels of 2,3,5,6-tetramethylpyrazine Following Transdermal Application

The Prediction of Plasma and Brain Levels of 2,3,5,6-tetramethylpyrazine Following Transdermal Application

Xiaohong Qi, Chrisita Ackermann, Duxin Sun, Rong Liu, Minli Sheng, Huimin Hou

AAPS PharmSci. 2002;4(4):E46.

PMID: 12646016

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 first-order-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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP1124114	2,3,5,6-Tetramethylpyrazine		1124-11-4	Price

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