The prediction of plasma and brain levels of 2,3,5,6-tetramethylpyrazine following transdermal application
Journal Title: The AAPS Journal - Year 2002, Vol 4, Issue 4
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.
Authors and Affiliations
Xiaohong Qi, Chrisita Ackermann, Duxin Sun, Rong (Ron) Liu, Minli Sheng, Huimin Hou
Keywords
Related Articles
- EP ID EP682052
- DOI 10.1208/ps040446
- Views 100
- Downloads 0
Mechanistic Modeling of Monocarboxylate Transporter-Mediated Toxicokinetic/Toxicodynamic Interactions Between γ-Hydroxybutyrate and l -Lactate
Overdose of γ-hydroxybutyrate (GHB) can result in severe respiratory depression. Monocarboxylate transporter (MCT) inhibitors, including l -lactate, increase GHB clearance and represent a potential treatment for...
A Bayesian Approach for Quantifying Trace Amounts of Antibody Aggregates by Sedimentation Velocity Analytical Ultracentrifugation
Sedimentation velocity analytical ultracentrifugation (SV-AUC) has become an important tool for the characterization of the purity of protein therapeutics. The work presented here addresses a need for methods orthogonal...
Drug Absorption Modeling as a Tool to Define the Strategy in Clinical Formulation Development
This article inadvertently failed to include two of the theme issue guest editors. The complete listing of the guest editors is shown in this erratum.
AAPS/RAPS/CAPRA collaborative program: Exploring the challenges of drug regulation in a global environment: Clinical concerns
Globalization of the pharmaceutical industry has led to a need to harmonize the regulatory requirements governing the marketing of medicinal products. To minimize the barriers impeding global drug product registration, t...
Population Pharmacokinetic/Pharmacodynamic Modeling of Guanfacine Effects on QTc and Heart Rate in Pediatric Patients
The online version of this article (doi:10.1208/s12248-014-9645-0) contains supplementary material, which is available to authorized users.